l Carnitine

Record 1 from database: MEDLINE
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Title

Carnitine metabolism in human subjects. II. Values of carnitine in biological fluids and tissues of "normal" subjects.

Author

Mitchell ME

Address

 

Source

Am J Clin Nutr, 1978 Mar, 31:3, 481-91

Abstract

Carnitine values in "normal" or "control" human subjects are assembled in the second part of this review. Data were found on blood, skeletal muscle, urine, heart muscle, and semen. Factors that affect these measures are related to the data.

Language of Publication

English

Unique Identifier

78121101

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MeSH Heading (Major)

Carnitine|BL/*ME/UR

MeSH Heading

Adolescence; Adult; Aged; Aging; Child; Diet; Exertion; Fasting; Female; Human; Male; Menstruation; Middle Age; Muscles|ME; Reference Values; Sex Factors

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0002-9165

Country of Publication

UNITED STATES

Record 2 from database: MEDLINE
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Title

Carnitine metabolism in chronic liver disease.

Author

Krähenbühl S

Address

Department of Internal Medicine, University Hospital, Zurich, Switzerland.

Source

Life Sci, 1996, 59:19, 1579-99

Abstract

The liver is a central organ for carnitine metabolism and for the distribution of carnitine to the body. It is therefore not surprising that carnitine metabolism is impaired in patients and experimental animals with certain types of chronic liver disease. In this review, the changes in carnitine metabolism associated with chronic liver disease and the role of carnitine as a therapeutic agent in some of these conditions are discussed.

Language of Publication

English

Unique Identifier

97070398

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MeSH Heading (Major)

Carnitine|*ME/TU; Fatty Liver|CO/*ME; Liver Cirrhosis|CI/DT/ET/*ME

MeSH Heading

Animal; Chronic Disease; Fatty Liver, Alcoholic|ME; Hepatitis, Viral, Human|CO; Human; Liver Cirrhosis, Alcoholic|ME; Liver Cirrhosis, Biliary|ME; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0024-3205

Country of Publication

ENGLAND

Record 3 from database: MEDLINE
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Title

Is carnitine essential in children?

Author

Giovannini M; Agostoni C; Salari PC

Address

Fifth Department of Paediatrics, University of Milan, Italy.

Source

J Int Med Res, 1991 Mar, 19:2, 88-102

Abstract

Carnitine has a fundamental biological role as a long-chain fatty acid carrier across the mitochondrial membrane and in ketone body formation. Although the body normally synthesizes carnitine, in certain circumstances such as total parenteral nutrition and haemodialysis a dietary supplement may be needed to maintain adequate levels. Several considerations suggest that carnitine is a truly essential nutrient in infancy and in other situations where the energy requirement is particularly high, e.g. pregnancy and breast feeding. There are, for example, congenital deficit syndromes due to enzymatic inadequacies. There is also the possible role of carnitine in serious metabolic disorders such as organic acidaemias and, above all, it has multiple physiological functions in major metabolic pathways which are essential for development and growth.

Language of Publication

English

Unique Identifier

91323648

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MeSH Heading (Major)

Carnitine|DF/*ME/TU

MeSH Heading

Animal; Comparative Study; Female; Human; Infant; Infant, Newborn; Kidney|ME; Liver|ME; Metabolism, Inborn Errors|PP; Milk, Human|CH; Nutritional Requirements; Pregnancy; Rats

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0300-0605

Country of Publication

ENGLAND

Record 4 from database: MEDLINE
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Title

Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy.

Author

Tein I; De Vivo DC; Bierman F; Pulver P; De Meirleir LJ; Cvitanovic Sojat L; Pagon RA; Bertini E; Dionisi Vici C; Servidei S; et al

Address

Division of Pediatric Neurology, Columbia University, New York, New York 10032.

Source

Pediatr Res, 1990 Sep, 28:3, 247-55

Abstract

Evidence is emerging that primary systemic carnitine deficiency, a potentially lethal but eminently treatable inborn error of fatty acid oxidation, involves a cellular defect in the uptake of carnitine. We present four unrelated children with primary carnitine-responsive cardiomyopathy, weakness (with or without hypoketotic hypoglycemic encephalopathy), low serum and/or tissue carnitine concentrations, and severe renal carnitine leak. Dicarboxylic acids were absent in the urine of three children who were tested, and all four had a rapid and dramatic improvement in cardiac function, strength, and somatic growth after carnitine therapy. We studied carnitine uptake in cultured skin fibroblasts from all four children and seven of the eight healthy nonconsanguinous parents. [3H]L-carnitine uptake was evaluated in vitro under linear time kinetics. Substrate concentrations were varied from 0.1 to 1000 microM. Physiologic uptake was determined at carnitine concentrations between 0.1 and 50 microM. Nonspecific uptake was determined at a concentration of 10 mM. The four patients had negligible uptake throughout the physiologic range, implying a marked deficiency in the specific high-affinity, low-concentration, carrier-mediated uptake mechanism. At a concentration of 5 mumol/L, the mean velocity of uptake in the four patients was 2% of control values. Their parents showed intermediate maximal rates of carnitine uptake ranging from 13 to 44% of control Vmax values, but normal Km values, suggesting that the heterozygotes had a reduced number of normal functioning carnitine transporters. The observed reduction in Vmax values for the parents supports an autosomal recessive inheritance pattern and may be a more sensitive indicator of heterozygosity than serum carnitine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

91044610

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MeSH Heading (Major)

Carnitine|*DF/ME/TU; Lipid Metabolism, Inborn Errors|CO/DT/*ME; Myocardial Diseases|DT/ET/*ME

MeSH Heading

Biological Transport, Active; Case Report; Child; Child, Preschool; Fatty Acids|ME; Female; Fibroblasts|ME; Human; Male; Skin|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0031-3998

Country of Publication

UNITED STATES

Record 5 from database: MEDLINE
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Title

Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa.

Author

Jeulin C; Lewin LM

Address

Laboratoire de Biologie de la Reproduction et du DÆeveloppment, Centre Hospitalier Universitaire, Le Kremlin-BicÈetre, France.

Source

Hum Reprod Update, 1996 Mar, 2:2, 87-102

Abstract

Spermatozoa are produced in the testis and undergo post-gonadal modifications in the epididymis to acquire fertilizing ability. In epididymal plasma, high-molecular-weight proteins and such small molecules as free-L carnitine convert the gametes into "competent' and functional cells. This review summarizes the knowledge pertaining to L-carnitine and the significance of free L-carnitine uptake into the mature spermatozoa of mammals. We provide an overview of the function of free L-carnitine and carnitine esters in the metabolism of eukaryotic cells and review the role of the specific carnitine acyltransferases in mitochondrial transport of fatty acids and in modulating acyl-coenzyme A (CoA) pools in cellular organelles. In mammals, including man, free L-carnitine is taken from blood plasma and concentrated in the epididymal lumen. This epididymal secretion is beneficial for spermatozoa and is not merely an excretory waste. The uptake of free L-carnitine into the spermatozoa and its metabolic outcome are discussed first in in-vivo and then in in-vitro situations. Free L-carnitine goes through the sperm plasma membrane by passive diffusion. Free L-carnitine is acetylated in mature spermatozoa only. The excess acetyl-CoA from the mitochondria is probably stored as acetyl-L-carnitine and modulates the reserves of free CoA essential to the function of the tricarboxylic acid cycle. These properties of L-carnitine of buffering CoA in the mitochondrial matrix are known in somatic cells but are accentuated in this study of the male germinal cells. In the future, a precise measurement of the in-vivo and in-vitro concentrations of free CoA and acetyl-CoA in the cellular compartments of immature and mature spermatozoa might complete these data. The relationship between the endogenous pools of free and acetylated L-carnitine and the percentage of progressive sperm motility indicates a more important metabolic function related to flagellar movement. In conclusion, the potential to initiate sperm motility, which takes place in the epididymis, is probably independent of the carnitine system, while the energy properties of acetyl-L-carnitine can only be relevant in situations of "energy crisis'. The uptake of "cytoplasmic' free L-carnitine in mature spermatozoa must be a protective form of mitochondrial metabolism, useful to the survival of this isolated cell.

Language of Publication

English

Unique Identifier

97233217

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MeSH Heading (Major)

Acetylcarnitine|*ME; Carnitine|*ME; Carnitine Acyltransferases|*ME; Sperm Maturation|*PH

MeSH Heading

Animal; Ejaculation; Epididymis|ME; Epithelium|ME; Human; Male; Semen|ME; Sperm Motility; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1355-4786

Country of Publication

ENGLAND

Record 6 from database: MEDLINE
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Title

Carnitine metabolism in human subjects. I. Normal metabolism.

Author

Mitchell ME

Address

 

Source

Am J Clin Nutr, 1978 Feb, 31:2, 293-306

Abstract

Carnitine (vitamin BT) is a compound which is involved with lipid metabolism. This article deals with the carnitine content of foods and diet, the absorption, transport, storage, and excretion of carnitine in humans. The metabolic functions and biosynthesis of carnitine are also reviewed.

Language of Publication

English

Unique Identifier

78100453

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MeSH Heading (Major)

Carnitine|*/AN/ME; Food Analysis|*

MeSH Heading

Absorption; Adult; Animal; Biological Transport; Carboxy-Lyases|ME; Carnitine O-Acetyltransferase|ME; Carnitine O-Palmitoyltransferase|ME; Child; Diet; Female; Human; Male; Nutritional Requirements

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0002-9165

Country of Publication

UNITED STATES

Record 7 from database: MEDLINE
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Title

Carnitine metabolism in human subjects. III. Metabolism in disease.

Author

Mitchell ME

Address

 

Source

Am J Clin Nutr, 1978 Apr, 31:4, 645-59

Abstract

Carnitine metabolism is reviewed in lipid storage myopathies, diabetes, vomiting sickness of Jamaica, malnutrition, hyperthyrodism, Duchenne dystrophy, and a few other disease states.

Language of Publication

English

Unique Identifier

78142111

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MeSH Heading (Major)

Carnitine|DF/*ME

MeSH Heading

Adolescence; Adult; Animal; Carnitine Acyltransferases|ME; Child; Diabetes Mellitus|PP; Diabetic Ketoacidosis|PP; Female; Gluconeogenesis|DE; Human; Hyperthyroidism|ME; Hypoglycins|PD/PO; Male; Middle Age; Muscular Diseases|ET; Muscular Dystrophy|ME; Plant Poisoning|PP

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0002-9165

Country of Publication

UNITED STATES

Record 8 from database: MEDLINE
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Title

The role of carnitine and carnitine supplementation during exercise in man and in individuals with special needs [see comments]

Author

Brass EP; Hiatt WR

Address

Department of Medicine, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance 90509, USA.

Source

J Am Coll Nutr, 1998 Jun, 17:3, 207-15

Abstract

Carnitine is critical for normal skeletal muscle bioenergetics. Carnitine has a dual role as it is required for long-chain fatty acid oxidation, and also shuttles accumulated acyl groups out of the mitochondria. Muscle requires optimization of both of these metabolic processes during peak exercise performance. Theoretically, carnitine availability may become limiting for either fatty acid oxidation or the removal of acyl-CoAs during exercise. Despite the theoretical basis for carnitine supplementation in otherwise healthy persons to improve exercise performance, clinical data have not demonstrated consistent benefits of carnitine administration. Additionally, most of the anticipated metabolic effects of carnitine supplementation have not been observed in healthy persons. The failure to demonstrate clinical efficacy of carnitine may reflect the complex pharmacokinetics and pharmacodynamics of carnitine supplementation, the challenges of clinical trial design for performance endpoints, or the adequacy of endogenous carnitine content to meet even extreme metabolic demands in the healthy state. In patients with end stage renal disease there is evidence of impaired cellular metabolism, the accumulation of metabolic intermediates and increased carnitine demands to support acylcarnitine production. Years of nutritional changes and dialysis therapy may also lower skeletal muscle carnitine content in these patients. Preliminary data have demonstrated beneficial effects of carnitine supplementation to improve muscle function and exercise capacity in these patients. Peripheral arterial disease (PAD) is also associated with altered muscle metabolic function and endogenous acylcarnitine accumulation. Therapy with either carnitine or propionylcarnitine has been shown to increase claudication-limited exercise capacity in patients with PAD. Further clinical research is needed to define the optimal use of carnitine and acylcarnitines as therapeutic modalities to improve exercise performance in disease states, and any potential benefit in healthy individuals.

Language of Publication

English

Unique Identifier

98291376

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MeSH Heading (Major)

Carnitine|*AD/TU; Dietary Supplements|*; Exercise|*PH

MeSH Heading

Atherosclerosis|DT; Clinical Trials; Energy Metabolism; Human; Kidney Failure, Chronic|DT; Muscle, Skeletal|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0731-5724

Country of Publication

UNITED STATES

Record 9 from database: MEDLINE
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Title

Carnitine metabolism and human carnitine deficiency.

Author

Tanphaichitr V; Leelahagul P

Address

Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Source

Nutrition, 1993 May, 9:3, 246-54

Abstract

Carnitine in the human body is derived from the intake of preformed dietary carnitine and biosynthesized carnitine, stemming from the metabolism of lysine and methionine. Carnitine is synthesized in liver and kidney, stored in skeletal muscle, and excreted mainly in urine. Carnitine has two main functions, i.e., transporting long-chain fatty acids into the mitochondrial matrix for beta-oxidation to provide cellular energy and modulating the rise in intramitochondrial acyl-CoA/CoA ratio, which relieves the inhibition of many intramitochondrial enzymes involving glucose and amino acid catabolism. Thus, the main consequence of carnitine deficiency is impaired energy metabolism. Human carnitine deficiency can be either hereditary or acquired. Hereditary carnitine deficiency can be grouped into three clinical entities: myopathic carnitine deficiency, systemic carnitine deficiency, and organic acidurias. Acquired carnitine deficiency is due to inadequate intake, increased requirement, and increased loss of carnitine. The definite diagnosis of carnitine deficiency is based on the determination of free- and acylcarnitine levels in serum, urine, and/or tissues. The estimated safe and adequate daily carnitine intake for adults is 150-500 mumol/day whereas pharmacological doses of carnitine are required for the treatment of hereditary carnitine deficiency.

Language of Publication

English

Unique Identifier

93357583

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MeSH Heading (Major)

Carnitine|*DF/*ME

MeSH Heading

Animal; Deficiency Diseases|PP; Human; Metabolism, Inborn Errors|PP; Nutritional Requirements

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0899-9007

Country of Publication

UNITED STATES

Record 10 from database: MEDLINE
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Title

Antioxidants, carnitine, and choline as putative ergogenic aids.

Author

Kanter MM; Williams MH

Address

Gatorade Sports Science Institute, Barrington, IL 60010, USA.

Source

Int J Sport Nutr, 1995 Jun, 5 Suppl:, S120-31

Abstract

Three nutritional products that have very different mechanisms of action are antioxidant vitamins, carnitine, and choline. Antioxidant vitamins do not appear to have a direct effect on physical performance in well-fed people but have been touted for their ability to detoxify potentially damaging free radicals produced during exercise. Carnitine purportedly enhances lipid oxidation, increases VO2max, and decreases plasma lactate accumulation during exercise. However, studies of carnitine do not generally support its use for ergogenic purposes. Choline supplements have been advocated as a means of preventing the decline in acetylcholine production purported to occur during exercise; this decline may reduce the transmission of contraction-generating impulses across the skeletal muscle, an effect that could impair one's ability to perform muscular work. However, there are no definitive studies in humans that justify choline supplementation. Much of the scientific data regarding the aforementioned nutrients are equivocal and contradictory. Their potential efficacy for improving physical performance remains largely theoretical.

Language of Publication

English

Unique Identifier

96018082

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MeSH Heading (Major)

Antioxidants|AD/*PD; Carnitine|AD/*PD; Choline|AD/*PD; Exertion|*DE/PH

MeSH Heading

Acetylcholine|ME; Food, Fortified; Human; Muscle, Skeletal|PH; Oxygen Consumption|PH

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1050-1606

Country of Publication

UNITED STATES

Record 11 from database: MEDLINE
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Title

Carnitine--a known compound, a novel function in neural cells.

Author

Na…ecz KA; Na…ecz MJ

Address

Department of Muscle Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland. KNAL@nencki.gov.pl

Source

Acta Neurobiol Exp (Warsz), 1996, 56:2, 597-609

Abstract

Carnitine (4-N-trimethylammonium-3-hydroxybutyric acid) seems to fulfill in the brain a different role than in peripheral tissues. Carnitine is accumulated by neural cells in a sodium-dependent way. The existence of a novel transporter in plasma membrane, specific to compounds with a polar group in the beta-position with respect to carboxyl group, has been postulated. The presence of a carnitine carrier in the inner mitochondrial membrane has been proven and the protein has been purified. It is postulated that its major role in adult brain would be translocation of acetyl moieties from mitochondria into the cytoplasm for acetylcholine synthesis. The latter process is stimulated by carnitine and choline in a synergistic way in cells utilizing glucose as the main energetic substrate. Carnitine metabolism in neural cells leads to accumulation of different acyl derivatives of carnitine. Palmitoylcarnitine can influence directly the activity of protein kinase C. An involvement of carnitine in a decrease of palmitate pool used for palmitoylation of regulatory proteins has been postulated.

Language of Publication

English

Unique Identifier

96333875

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MeSH Heading (Major)

Brain|*PH; Carnitine|ME/*PH; Neurons|*PH

MeSH Heading

Acetylcholine|ME; Adult; Animal; Biological Transport; Choline|PH; Human; Intracellular Membranes|ME; Mitochondria|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0065-1400

Country of Publication

POLAND

Record 12 from database: MEDLINE
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Title

Carnitine palmitoyltransferase deficiency in a college athlete: a case report and literature review.

Author

Faigel HC

Address

University Health Services, Brandeis University, USA.

Source

J Am Coll Health, 1995 Sep, 44:2, 51-4

Abstract

Type II carnitine palmitoyltransferase deficiency is the most common cause of exercise-induced rhabdomyolysis, myoglobinuria, and proximal muscle weakness and pain in young adults. A lack of this enzyme impairs mitochondrial oxidation of long-chain fatty acids and can lead to rhabdomyolysis, myoglobinuria, and renal failure. Carnitine palmitoyltransferase deficiency, unusual but not rare, is often detected by finding elevated creatine phosphokinase level in a routine blood chemistry panel. A case of carnitine palmitoyltransferase deficiency in a college athlete is presented, and the disorder is compared with defective myophosphorylation in McArdle's disease, the next most frequent cause of similar symptoms.

Language of Publication

English

Unique Identifier

96019565

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MeSH Heading (Major)

Carnitine O-Palmitoyltransferase|*DF; Kidney Failure, Acute|*CO; Myoglobinuria|*CO; Rhabdomyolysis|*CO

MeSH Heading

Adolescence; Case Report; Diagnosis, Differential; Exercise; Female; Glycogen Storage Disease Type V|CO/EN/GE; Human; Mitochondrial Myopathies|CO/EN/GE; Phosphorylation

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE

ISSN

0744-8481

Country of Publication

UNITED STATES

Record 13 from database: MEDLINE
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Title

New insights into the mitochondrial carnitine palmitoyltransferase enzyme system.

Author

McGarry JD; Sen A; Esser V; Woeltje KF; Weis B; Foster DW

Address

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.

Source

Biochimie, 1991 Jan, 73:1, 77-84

Abstract

Dissection of the mitochondrial carnitine palmitoyltransferase (CPT) enzyme system in terms of its structure/function relationships has proved to be a formidable task. Although no one formulation has gained universal agreement we believe that the weight of evidence supports a model with the following features: a) in any given tissue CPT I and CPT II are distinct proteins; b) CPT I, unlike CPT II, is detergent labile; c) within a species CPT II is expressed body wide, whereas CPT I exists as tissue specific isoforms; d) malonyl-CoA and other CPT I inhibitors probably interact at the catalytic center of the enzyme, not with a regulatory subunit. The amino acid sequences of rat and human CPT II (deduced from cDNA clones) show them to be similar proteins (greater than 80% identity) but encoded by mRNAs of significantly different sizes. Efforts to clone and sequence the cDNA for rat liver CPT I are presently underway.

Language of Publication

English

Unique Identifier

91234776

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MeSH Heading (Major)

Carnitine O-Palmitoyltransferase|CH/*ME; Mitochondria|*EN

MeSH Heading

Amino Acid Sequence; Animal; Human; Isoenzymes|ME; Malonyl Coenzyme A|ME/PD; Mitochondria, Heart|EN; Mitochondria, Liver|EN; Mitochondria, Muscle|EN; Models, Biological; Molecular Sequence Data; Structure-Activity Relationship

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0300-9084

Country of Publication

FRANCE

Record 14 from database: MEDLINE
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Title

L-carnitine in dialysed patients: the choice of dosage regimen.

Author

Berard E; Iordache A; Barrillon D; Bayle J

Address

Department of Nephrology, University Hospital of Nice, France.

Source

Int J Clin Pharmacol Res, 1995, 15:3, 127-33

Abstract

Although carnitine levels and carnitine therapy have been extensively studied in dialysis patients, the pathophysiology of L-carnitine is poorly understood. The usual therapeutic dose is 20-30 mg/kg, resulting in dramatic increases of circulating levels above the normal values. Guided by studies on its lipidic effect and by our experience of its action on haematocrit, we propose the use of 2-3 mg/kg of L-carnitine in future prospective studies.

Language of Publication

English

Unique Identifier

96274618

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MeSH Heading (Major)

Carnitine|AD/ME/*TU; Hemodialysis|*AE; Kidney Failure, Chronic|*CO/TH

MeSH Heading

Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0251-1649

Country of Publication

SWITZERLAND

Record 15 from database: MEDLINE
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Title

Pyruvate and hydroxycitrate/carnitine may synergize to promote reverse electron transport in hepatocyte mitochondria, effectively 'uncoupling' the oxidation of fatty acids.

Author

McCarty MF; Gustin JC

Address

NutriGuard Research, Encinitas, CA 92024, USA.

Source

Med Hypotheses, 1999 May, 52:5, 407-16

Abstract

In a recent pilot study, joint administration of pyruvate, hydroxycitrate (HCA), and carnitine to obese subjects was associated with a remarkable rate of body-fat loss and thermogenesis, strongly suggestive of uncoupled fatty-acid oxidation. Hepatocytes possess an uncoupling mechanism--reverse electron transport--that enables fasting ketogenesis to proceed independent of respiratory control. Electrons entering the respiratory chain at the coenzyme Q (CoQ) level via FAD-dependent acyl coA dehydrogenase, can be driven 'up' the chain by the electrochemical proton gradient to reduce NAD+; if these electrons are then shuttled to the cytoplasm, returning to the respiratory chain at the CoQ level, the net result is heat generation at the expense of the proton gradient, enabling the uncoupled flow of electrons to oxygen. Pyruvate's bariatric utility may stem from its ability to catalyze the rapid transport of high-energy electrons from mitochondria to the cytoplasm, thus stimulating electron shuttle mechanisms. By enabling rapid mitochondrial uptake of fatty acids and thus disinhibiting hepatocyte ketogenesis, HCA/carnitine should initiate reverse electron transport: concurrent amplification of electron shuttle mechanisms by pyruvate can be expected to accelerate this reverse electron transport, thereby decreasing the electrochemical proton gradient. As a result, hepatocytes may be able to convert fatty acids to CO2 and heat with little net generation of ATP. These considerations suggest that it may be feasible to render hepatocytes functionally equivalent to activated brown fat, such that stored fat can be selectively oxidized in the absence of caloric restriction. Other measures which enhance the efficiency of hepatocyte electron shuttle mechanisms may increase the efficacy of this strategy.

Language of Publication

English

Unique Identifier

99343391

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MeSH Heading (Major)

Carnitine|*PD; Citrates|*PD; Electron Transport|*DE; Mitochondria, Liver|DE/*ME; Pyruvates|*PD

MeSH Heading

Animal; Body Temperature Regulation; Drug Synergism; Fatty Acids, Nonesterified|ME; Glucagon|PH; Human; Models, Biological; Pilot Projects; Ubiquinone|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0306-9877

Country of Publication

ENGLAND

Record 16 from database: MEDLINE
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Title

Carnitine supplementation in soy-based formula-fed infants.

Author

Novak M

Address

Department of Pediatrics, University of Miami School of Medicine, Fla.

Source

Biol Neonate, 1990, 58 Suppl 1:, 89-92

Abstract

Gradual increase of carnitine in plasma, tissues and urine after birth is a normal response of breast-fed infants and those receiving carnitine-containing formulas. Marked reduction of carnitine and acylcarnitines was noted in infants given diets not containing carnitine. These differences prompted the evaluation of the rationale for adding carnitine into soy-based formulas. In healthy term infants the lack of dietary carnitine did not induce deficiency symptoms but reduced the uptake of fatty acids for beta-oxidation. The cumulative effect of various metabolic disorders and carnitine deficient diets may culminate to carnitine deficiency.

Language of Publication

English

Unique Identifier

91091454

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MeSH Heading (Major)

Carnitine|*AD/BL/DF/UR; Infant Food|*; Infant Nutrition|*; Vegetable Proteins|*

MeSH Heading

Fatty Acids|ME; Human; Infant, Newborn

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0006-3126

Country of Publication

SWITZERLAND

Record 17 from database: MEDLINE
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Title

Primary and secondary carnitine deficiency syndromes.

Author

Pons R; De Vivo DC

Address

Department of Neurology, Colleen Giblin Laboratories for Pediatric Neurology Research, Columbia-Presbyterian Medical Center, New York, NY, USA.

Source

J Child Neurol, 1995 Nov, 10 Suppl 2:, S8-24

Abstract

The objective of this article is to review primary and secondary causes of carnitine deficiency, emphasizing recent advances in our knowledge of fatty acid oxidation. It is now understood that the cellular metabolism of fatty acids requires the cytosolic carnitine cycle and the mitochondrial beta-oxidation cycle. Carnitine is central to the translocation of the long chain acyl-CoAs across the inner mitochondrial membrane. The mitochondrial beta-oxidation cycle is composed of a newly described membrane-bound system and the classic matrix compartment system. Very long chain acyl-CoA dehydrogenase and the trifunctional enzyme complex are embedded in the inner mitochondrial membrane, and metabolize the long chain acyl-CoAs. The chain shortened acyl-CoAs are further degraded by the well-known system in the mitochondrial matrix. Numerous metabolic errors have been described in the two cycles of fatty acid oxidation; all are transmitted as autosomal recessive traits. Primary or secondary carnitine deficiency is present in all these clinical conditions except carnitine palmitoyltransferase type I and the classic adult form of carnitine palmitoyltransferase type II deficiency. The sole example of primary carnitine deficiency is the genetic defect involving the active transport across the plasmalemmal membrane. This condition responds dramatically to oral carnitine therapy. The secondary carnitine deficiencies respond less obviously to carnitine replacement. These conditions are managed by high carbohydrate, low fat frequent feedings, and vitamin/cofactor supplementation (eg, carnitine, glycine, and riboflavin). Medium chain triglycerides may be useful in the dietary management of patients with inborn errors of the cytosolic carnitine cycle or the mitochondrial membrane-bound long chain specific beta-oxidation system.

Language of Publication

English

Unique Identifier

96155687

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MeSH Heading (Major)

Carnitine|*ME; Vitamin B Deficiency|*ME

MeSH Heading

Animal; Enzyme Activation; Fatty Acids|ME; Human; Mitochondria|ME; Risk Factors; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0883-0738

Country of Publication

UNITED STATES

Record 18 from database: MEDLINE
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Title

Carnitine in human immunodeficiency virus type 1 infection/acquired immune deficiency syndrome.

Author

Mintz M

Address

University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School at Camden 08103, USA.

Source

J Child Neurol, 1995 Nov, 10 Suppl 2:, S40-4

Abstract

There is an increasing body of evidence that subgroups of patients infected with human immunodeficiency virus type 1 possess carnitine deficiency. Secondary carnitine deficiencies in these individuals may result from nutritional deficiencies, gastrointestinal disturbances, renal losses, or shifts in metabolic pathways. However, tissue depletion precipitated by drug toxicities, particularly zidovudine, is a major etiology and concern. Carnitine deficiency may impact on energy and lipid metabolism, causing mitochondrial and immune dysfunction. There are convincing laboratory data showing the in vitro ameliorative effects of L-carnitine supplementation of zidovudine-induced myopathies and lymphocyte function. Studies measuring the impact of L-carnitine supplementation on clinical characteristics are ongoing.

Language of Publication

English

Unique Identifier

96155690

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MeSH Heading (Major)

Carnitine|*ME; HIV Infections|*ME; HIV-1|*; Vitamin B Deficiency|*ME

MeSH Heading

Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0883-0738

Country of Publication

UNITED STATES

Record 19 from database: MEDLINE
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Title

Carnitine deficiency in epilepsy: Risk factors and treatment.

Author

Coulter DL

Address

Department of Pediatrics, Boston University School of Medicine, MA, USA.

Source

J Child Neurol, 1995 Nov, 10 Suppl 2:, S32-9

Abstract

Numerous studies have shown that plasma carnitine levels are significantly lower in patients taking valproate than in controls. Free carnitine deficiency is not uncommon in these patients and also occurs in newborns with seizures and in patients taking other anticonvulsant drugs. Carnitine deficiency in epilepsy results from a variety of etiologic factors including underlying metabolic diseases, nutritional inadequacy, and specific drug effects. The relationship between carnitine deficiency and valproate-induced hepatotoxicity is unclear. Carnitine treatment does not always prevent the emergence of serious hepatotoxicity, but it does alleviate valproate-induced hyperammonemia. These studies suggest that specific risk factors for carnitine deficiency can be identified. Preliminary data suggest that carnitine treatment may benefit high-risk, symptomatic patients and those with free carnitine deficiency. Carnitine treatment is not likely to benefit low-risk, asymptomatic patients and those with normal carnitine levels.

Language of Publication

English

Unique Identifier

96155689

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MeSH Heading (Major)

Carnitine|*ME; Epilepsy|DT/*ME; Vitamin B Deficiency|*ME

MeSH Heading

Human; Liver|DE; Risk Factors; Valproic Acid|TU

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0883-0738

Country of Publication

UNITED STATES

Record 20 from database: MEDLINE
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Title

Biosynthesis and metabolism of carnitine.

Author

Carter AL; Abney TO; Lapp DF

Address

Department of Biochemistry, Medical College of Georgia, Augusta 30912-2100, USA.

Source

J Child Neurol, 1995 Nov, 10 Suppl 2:, S3-7

Abstract

This review article presents the biosynthesis, metabolism, sources, levels, and general functions of carnitine. Emphasis is placed on the expression of carnitine deficiency and insufficiency as well as the causes of these conditions. The various functions of carnitine are discussed as they may relate to disease treatment.

Language of Publication

English

Unique Identifier

96155686

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MeSH Heading (Major)

Carnitine|*BI/*ME

MeSH Heading

Animal; Chemistry; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0883-0738

Country of Publication

UNITED STATES

Record 21 from database: MEDLINE
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Title

Carnitine in neonatal nutrition.

Author

Borum PR

Address

Department of Food Science and Human Nutrition, University of Florida, Gainesville 32611-0370, USA.

Source

J Child Neurol, 1995 Nov, 10 Suppl 2:, S25-31

Abstract

Experimental evidence from several investigators suggests that carnitine is a conditionally essential nutrient for neonates. If carnitine is a conditionally essential nutrient for the neonate, most neonates on total parenteral nutrition in the United States are not receiving adequate nutritional support. The metabolic functions of carnitine are varied and important in several aspects of neonatal physiology. All neonates receiving breast milk receive dietary carnitine and most neonates receiving enteral infant formulas receive dietary carnitine at a level similar to that of the breast-fed neonate. However, most neonates on total parenteral nutrition receive no dietary carnitine. Investigators have been testing the working hypothesis that carnitine is a conditionally essential nutrient for the neonate for many years. This review discusses (1) data supporting the hypothesis, (2) reasons why it has not been either proved or disproved by now, and (3) the author's view of a prudent approach to dietary carnitine supplementation of neonates.

Language of Publication

English

Unique Identifier

96155688

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MeSH Heading (Major)

Carnitine|*ME; Vitamin B Deficiency|*ME

MeSH Heading

Age Factors; Animal; Animals, Newborn; Child Nutrition; Human; Infant, Newborn

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0883-0738

Country of Publication

UNITED STATES

Record 22 from database: MEDLINE
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Title

Expression and regulation of carnitine palmitoyltransferase-Ialpha and -Ibeta genes.

Author

Cook GA; Park EA

Address

Department of Pharmacology, College of Medicine, The University of Tennessee, Memphis 38163, USA. gcook@utmem1.utmem.edu

Source

Am J Med Sci, 1999 Jul, 318:1, 43-8

Abstract

Two genes control expression of mitochondrial carnitine palmitoyltransferase-I (CPT-I), the enzyme that catalyzes the primary rate-controlling step in fatty acid oxidation. Two CPT-I isoforms have been found--a "liver" isoform (CPT-Ialpha) expressed in most tissues, but not in skeletal muscles, and a "muscle" isoform (CPT-Ibeta) expressed in muscles and adipocytes. Liver CPT-Ialpha increases dramatically at birth, but heart CPT-Ialpha is abundant in the fetus and diminishes at birth. Insulin, thyroid hormone, and fatty acids regulate expression of CPT-Ialpha in liver, whereas electrical stimulation increases CPT-Ibeta and decreases CPT-Ialpha in cardiac myocytes. Both genes are TATA-less and contain Sp1 transcription factor binding sites upstream of the start site of transcription. Multiple transcripts of both CPT-Ialpha and CPT-Ibeta exist, some of which may have roles in regulating fatty acid oxidation.

Language of Publication

English

Unique Identifier

99335245

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MeSH Heading (Major)

Carnitine O-Palmitoyltransferase|*GE; Fatty Acids|*ME; Gene Expression Regulation, Enzymologic|*; Mitochondria|*EN

MeSH Heading

Animal; Human; Isoenzymes|GE; Mitochondria, Heart|EN; Mitochondria, Liver|EN; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-9629

Country of Publication

UNITED STATES

Record 23 from database: MEDLINE
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Title

The role of the carnitine system in peroxisomal fatty acid oxidation.

Author

Ramsay RR

Address

School of Biomedical Sciences, University of St. Andrews, Fife, UK. rrr@st-and.ac.uk

Source

Am J Med Sci, 1999 Jul, 318:1, 28-35

Abstract

Peroxisomes are small, subcellular organelles that play a major role in lipid metabolism. Inherited disorders of peroxisomal structure and metabolism can result from defective assembly, missing protein import transporters, or individual enzyme deficiencies. Molecular studies helped by the range of disorders have now elucidated many of the pathways, including the paths of alpha-oxidation for phytanic acid and beta-oxidation for very-long-chain and branched-chain fatty acids and for bile acid synthesis. The mechanism of the transfer of substrates, intermediates, and products across the membrane is poorly understood. The carnitine system, known to transport activated acyl groups between localized coenzyme A pools, is presented. The evidence for the involvement of carnitine in the transfer of activated acyl groups to and from the peroxisomes is reviewed.

Language of Publication

English

Unique Identifier

99335243

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MeSH Heading (Major)

Carnitine|*ME; Fatty Acids|*ME; Microbodies|*ME

MeSH Heading

Animal; Human; Lipid Peroxidation; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-9629

Country of Publication

UNITED STATES

Record 24 from database: MEDLINE
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Title

Carnitine-acylcarnitine translocase deficiency.

Author

Pande SV

Address

Laboratory of Intermediary Metabolism, Clinical Research Institute of Montreal, Quebec, Canada. spande@sprint.ca

Source

Am J Med Sci, 1999 Jul, 318:1, 22-7

Abstract

Carnitine-acylcarnitine translocase deficiency, like other defects of mitochondrial fatty acid oxidation, is an autosomal, recessively inherited disorder. When the deficiency is near total, it is usually fatal, affects life soon after birth, and constitutes one of the causes of skeletal muscle myopathy, cardiac and liver abnormalities, and childhood sudden death. The presenting features have included neonatal distress, convulsions, hypoglycemia, hyperammonemia, hypoketonemia, intermittent dicarboxyluria, hypothermia, apnea, neurological deterioration, and hypocarnitinemia with grossly elevated acylcarnitines. Two cases of partial translocase deficiency (4-6% residual activity) with milder symptoms and without cardiac involvement have also been identified. Evidence so far indicates that the translocase protein is the product of a single gene. In two cases of translocase deficiency, the accompanying mutations have been identified. The benefits of prenatal diagnosis have been provided to the affected families by assays of the translocase and/or fatty acid oxidation in cultured amniotic/villous cells. In one such case genetic counseling was made possible even when the only specimen available from a deceased sibling was the Guthrie card.

Language of Publication

English

Unique Identifier

99335242

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MeSH Heading (Major)

Carnitine Acyltransferases|*DF; Metabolism, Inborn Errors|CO/*DI/*EN

MeSH Heading

Diagnosis, Differential; Fatty Acids|ME; Human; Infant, Newborn; Prenatal Diagnosis; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-9629

Country of Publication

UNITED STATES

Record 25 from database: MEDLINE
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Title

Primary and secondary alterations of neonatal carnitine metabolism.

Author

Scaglia F; Longo N

Address

Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.

Source

Semin Perinatol, 1999 Apr, 23:2, 152-61

Abstract

Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane, in the detoxification of acyl moieties, and in maintaining normal levels of free coenzyme A. Although carnitine can be synthesized in liver and kidney, normal adults obtain the majority of carnitine from the diet. Preterm newborns have a reduced capacity to synthesize carnitine. Total parenteral nutrition lacks carnitine and exposes very low birth weight infants to carnitine deficiency, with decreased production of ketones from long-chain fatty acids. Supplementation with low doses of carnitine improves nitrogen balance and growth in these infants. Carnitine deficiency can be part of a number of inherited and acquired diseases. Primary carnitine deficiency is an autosomal recessive disorder characterized by increased losses of carnitine in the urine and decreased accumulation in the heart and skeletal muscle caused by defective carnitine transport. This condition is corrected by high-dose carnitine supplementation. Secondary carnitine deficiency can be caused by increased losses, pharmacological therapy, or a number of inherited metabolic disorders that must be correctly diagnosed before initiating carnitine supplementation.

Language of Publication

English

Unique Identifier

99260309

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MeSH Heading (Major)

Carnitine|AD/*DF/*ME

MeSH Heading

Diet; Fatty Acids|ME; Human; Infant, Newborn; Metabolism, Inborn Errors|DI/TH; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0146-0005

Country of Publication

UNITED STATES

Record 26 from database: MEDLINE
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Title

The roles of glucose-induced metabolic hypoxia and imbalances in carnitine metabolism in mediating diabetes-induced vascular dysfunction.

Author

Williamson JR; Arrigoni Martelli E

Address

Department of Pathology, Washington University School of Medicine, St. Louis.

Source

Int J Clin Pharmacol Res, 1992, 12:5-6, 247-52

Abstract

Investigations were initiated to examine the rate of imbalances in carnitine metabolism in the pathogenesis of diabetic vascular changes in the retina, peripheral nerves, aorta and kidney. It appears that glucose/diabetes-induced vascular dysfunction and early vascular structural changes are mediated by hyperglycaemic hypoxia i.e. glucose-induced metabolic imbalances that cause an increase in the reduced nicotinamide-adenine dinucleotide/nicotinic acid dehydrogenase ratio, and are linked to imbalances in carnitine metabolism.

Language of Publication

English

Unique Identifier

93246324

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MeSH Heading (Major)

Blood Glucose|*ME; Carnitine|*ME; Cell Hypoxia|*; Diabetic Angiopathies|*ET/ME

MeSH Heading

Animal; Human; NAD|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0251-1649

Country of Publication

SWITZERLAND

Record 27 from database: MEDLINE
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Title

Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of beta-oxidation.

Author

Angelini C; Vergani L; Martinuzzi A

Address

Regional Neuromuscular Center, University of Padova, Italy.

Source

Crit Rev Clin Lab Sci, 1992, 29:3-4, 217-42

Abstract

Carnitine is required for entry of long chain fatty acids into mitochondria where beta-oxidation occurs. Primary carnitine deficiency, due to a generic defect in cellular carnitine transport, exists in myopathic and systemic forms. Secondary carnitine deficiency may be due to multiplicity of inherited abnormalities, including deficiencies in carnitine palmitoyl-transferase acyl-CoA dehydrogenases, electron transfer flavoprotein, and 3-ketoacyl-CoA-thiolase. The clinical features, diagnosis, and treatment of these conditions are described.

Language of Publication

English

Unique Identifier

93143862

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MeSH Heading (Major)

Carnitine|*DF/ME; Vitamin B Deficiency|*ME

MeSH Heading

Biological Transport, Active; Fatty Acids|ME; Human; Metabolism, Inborn Errors|ME; Mitochondria|ME; Oxidation-Reduction; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1040-8363

Country of Publication

UNITED STATES

Record 28 from database: MEDLINE
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Title

Biological roles of L-carnitine in perinatal metabolism.

Author

Arenas J; Rubio JC; Martín MA; Campos Y

Address

Centro de InvestigaciÆon Hospital Universitario 12 de Octubre, Madrid, Spain. jarenas@h12o.es

Source

Early Hum Dev, 1998 Dec, 53 Suppl:, S43-50

Abstract

Carnitine performs a crucial role in the energy supply of tissues during fetal life and in the neonatal period by controlling the influx of fatty acids into mitochondria. Carnitine also facilitates the oxidation of pyruvate and branched chain amino acids, and contributes to the protection of cells from the deleterious actions of acyl CoAs. Carnitine further acts as a secondary antioxidant, favouring fatty acid replacement within previously oxidatively damaged membrane phospholipids. Availability of L-carnitine is essential in the developing fetus for processes underlying fetal maturation. L-carnitine is also essential for development of hepatic ketone synthesis, a central pathway for neonatal energy metabolism. Ketone bodies inhibit the oxidation of both glucose and lactate, sparing these metabolic substrates for biosynthetic functions.

Language of Publication

English

Unique Identifier

99200799

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MeSH Heading (Major)

Carnitine|*PH; Fetus|*ME

MeSH Heading

Energy Metabolism; Fatty Acids, Nonesterified|ME; Human; Infant, Newborn; Ketone Bodies|ME; Liver|ME; Mitochondria|ME; Oxidation-Reduction; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0378-3782

Country of Publication

IRELAND

Record 29 from database: MEDLINE
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Title

Pharmacokinetic considerations for the therapeutic use of carnitine in hemodialysis patients.

Author

Brass EP

Address

Department of Medicine, Harbor-UCLA Medical Center, Torrance, USA.

Source

Clin Ther, 1995 Mar, 17:2, 176-85; discussion 175

Abstract

Clinical observations have suggested that carnitine supplementation may be beneficial to a subset of patients receiving chronic hemodialysis. In the absence of definitive clinical trials, the clinician must decide for an individual patient whether a trial of carnitine therapy is justified. The institution of carnitine therapy is further complicated by the availability of oral and intravenous dosing forms and by the compound's complex pharmacokinetics. The oral systemic bioavailability of carnitine in normal subjects is 5% to 16%, with peak plasma carnitine concentrations reached 2 to 6 hours after dosing. Carnitine is initially distributed into extracellular water and then more slowly enters tissue compartments with complex kinetics. Elimination of carnitine is through the urine or dialysate. Intravenous carnitine administration results in large peak plasma concentrations and assures systemic bioavailability. Orally administered carnitine has been reported to have clinical efficacy in hemodialysis patients in doses of 2 to 4 g per day in divided doses. Intravenous carnitine has also been widely used in clinical trials in attempts to demonstrate efficacy in the hemodialysis population; however, the available data do not establish the superiority of the intravenous formulation over the oral form. Intravenous carnitine may have theoretical advantages in initiating treatment when high peak concentrations are required to facilitate carnitine reaching nonhepatic tissue sites or when oral carnitine therapy is not feasible due to poor tolerance or compliance. Although comparative trials are lacking, it is probable that oral therapy can be used for long-term maintenance, regardless of which formulation was used to initiate therapy. The decision to use carnitine therapy, as well as the dose and route of administration, requires individualization based on the clinical status of the patient and the goals of therapy.

Language of Publication

English

Unique Identifier

95339370

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MeSH Heading (Major)

Carnitine|*AD/*PK; Hemodialysis|*; Kidney Failure, Chronic|*ME

MeSH Heading

Biological Availability; Human; Muscles|ME; Tissue Distribution

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0149-2918

Country of Publication

UNITED STATES

Record 30 from database: MEDLINE
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Title

Carnitine function and requirements during the life cycle.

Author

Rebouche CJ

Address

Department of Pediatrics, University of Iowa, Iowa City 52242.

Source

FASEB J, 1992 Dec, 6:15, 3379-86

Abstract

L-Carnitine has been described as a "conditionally essential" nutrient for humans. Segments of the human population suggested as having a requirement for carnitine include infants (premature and full-term), patients on long-term parenteral nutrition, and perhaps children. The evidence to support these claims includes 1) low circulating carnitine concentrations; 2) abnormal (or at least different) circulating metabolite concentrations (free fatty acids, triglycerides, ketone bodies), and 3) very limited and inconsistent growth data. A number of subjective observations and anecdotal case reports have been offered in support of a requirement for carnitine. Exogenous carnitine is required to maintain "normal" (in the epidemiologic sense) plasma or serum carnitine concentrations in humans of all ages. But "functional carnitine deficiency," defined by abnormal clinical presentation correctable by carnitine administration, has not been demonstrated in an otherwise normal (nonpathologic) population. On the other hand, nutritional or pharmacological intervention with carnitine or its esters may be beneficial for very premature infants, infants and children with various clinical conditions associated with low circulating carnitine concentrations, and in some chronic diseases associated with the aging process.

Language of Publication

English

Unique Identifier

93099945

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MeSH Heading (Major)

Aging|*PH; Carnitine|*PH; Nutrition|*

MeSH Heading

Adolescence; Adult; Aged; Animal; Child; Child, Preschool; Female; Human; Infant; Infant, Newborn; Male; Middle Age

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0892-6638

Country of Publication

UNITED STATES

Record 31 from database: MEDLINE
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Title

Carnitine palmitoyltransferase: a viable target for the treatment of NIDDM?

Author

Anderson RC

Address

Novartis Pharmaceuticals Corporation, Department of Metabolic and Cardiovascular Diseases, Summit, NJ 07901, USA.

Source

Curr Pharm Des, 1998 Feb, 4:1, 1-16

Abstract

Inhibition of fatty acid oxidation is well recognized as a potentially effective mechanism for controlling glycemia in non-insulin-dependent diabetes mellitus (NIDDM). However, a direct targeting of inhibition of the intramitochondrial beta-oxidation pathway or an indirect modulation of fatty acid oxidation by inhibition of substrate release from adipose stores has been fraught with lack of efficacy, unacceptable side-effects or both. Focus has therefore recently been directed towards the carnitine palmitoyltransferase (CPT) system, a three-component system necessary for the transfer of long-chain fatty acids into the intramitochondrial matrix. This article will briefly review the background for fatty acid oxidation inhibition in NIDDM and then focus on the progress in the biological understanding and drug discovery targeting of the CPT system for the treatment of NIDDM. Based upon the review, it is concluded that mechanism-based hepatic and myocardial toxicities in normal animals and a potential for a lack of human efficacy may pose insurmountable hurdles for the development of CPT inhibitors for the treatment of NIDDM.

Language of Publication

English

Unique Identifier

99212779

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MeSH Heading (Major)

Carnitine O-Palmitoyltransferase|*AI; Diabetes Mellitus, Non-Insulin-Dependent|*DT; Enzyme Inhibitors|*PD/TU; Fatty Acids|*ME; Mitochondria|*ME

MeSH Heading

Animal; Carnitine Acyltransferases|AI; Human; Malonyl Coenzyme A|AI; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

1381-6128

Country of Publication

NETHERLANDS

Record 32 from database: MEDLINE
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Title

Protection of the brain by carnitine.

Author

Igisu H; Matsuoka M; Iryo Y

Address

Department of Environmental Toxicology, University of Occupational and Environmental Health, Kitakyushu, Japan.

Source

Sangyo Eiseigaku Zasshi, 1995 Mar, 37:2, 75-82

Abstract

Carnitine (beta-hydroxy-gamma-trimethylammonium butyrate) is widely distributed in the body including the nervous system. Its physiological function, viz. a carrier of long-chain fatty acids through the inner mitochondrial membrane, has been well established. In this review, mainly based on our experiments, we discuss the possibility that carnitine may have effects other than the "physiological" function and that it may be a potent protector of the brain. When mice were exposed to ammonia (intraperitoneal injection of ammonium acetate), they developed seizures and concentrations of brain energy metabolites were altered; ATP and phosphocreatine decreased while ADP, AMP, pyruvate and lactate increased. The seizures and changes in brain energy metabolites were clearly suppressed when the mice were pre-treated with carnitine. Furthermore, changes in energy metabolites in the brain caused by severe ischemia (decapitation) were also suppressed by carnitine. Since D-carnitine showed similar effects as those of L-carnitine, the effects seem due to function(s) of carnitine yet to be defined. Intrinsic substances including carnitine appear to deserve further studies for possible use in protecting the brain.

Language of Publication

English

Unique Identifier

95269148

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MeSH Heading (Major)

Brain|DE/*ME; Carnitine|*PH

MeSH Heading

Ammonia|TO; Animal; Cerebral Ischemia|PC; Energy Metabolism; Human; Mice; Seizures|CI/PC; Taurine|PH

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1341-0725

Country of Publication

JAPAN

Record 33 from database: MEDLINE
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Title

Fatal carnitine palmitoyltransferase II deficiency in a newborn: new phenotypic features.

Author

Pierce MR; Pridjian G; Morrison S; Pickoff AS

Address

Department of Pediatrics, Hayward Genetics Center, USA.

Source

Clin Pediatr (Phila), 1999 Jan, 38:1, 13-20

Abstract

We describe the term male infant of asymptomatic, healthy nonconsanguineous parents presenting on the first day of life with nonketotic hypoglycemia, seizures, hepatomegaly, cardiomegaly with biventricular hypertrophy, and ventricular arrhythmias. Cranial ultrasound revealed cystic dysplasia with several foci of hyperechogenicity within the right basal ganglia. Free carnitine was markedly decreased in the urine and plasma with a pronounced elevation of plasma long-chain acylcarnitines. Fibroblast carnitine palmitoyltransferase II activity was reduced to 26% and 38% in the father and mother, respectively. The infant expired on day 5 of life from malignant ventricular tachy-arrhythmias. Diffuse lipid accumulation was evident at autopsy, including in the liver, heart, kidney, adrenal cortex, skeletal muscle, and lungs. This new case of infantile CPT-II deficiency illustrates the severity of the early onset form of CPT-II deficiency.

Language of Publication

English

Unique Identifier

99123712

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MeSH Heading (Major)

Carnitine O-Palmitoyltransferase|*DF

MeSH Heading

Abnormalities, Multiple|GE; Case Report; Deficiency Diseases|GE/MO; Fatal Outcome; Human; Infant, Newborn; Male; Phenotype

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE

ISSN

0009-9228

Country of Publication

UNITED STATES

Record 34 from database: MEDLINE
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Title

Rate-dependent distal renal tubular acidosis and carnitine palmitoyltransferase I deficiency.

Author

Bergman AJ; Donckerwolcke RA; Duran M; Smeitink JA; Mousson B; Vianey Saban C; Poll The BT

Address

Department of Metabolic Diseases, University Children's Hospital, Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.

Source

Pediatr Res, 1994 Nov, 36:5, 582-8

Abstract

An infant girl presented with recurrent episodes of Reye-like syndrome associated with hypoketosis and plasma carnitine levels in the high-normal range. A liver biopsy revealed massive macrovesicular steatosis. Ketogenesis was absent after a long-chain triglyceride loading test; in contrast, the medium-chain triglyceride loading test resulted in a brisk rise in plasma ketone concentration. Carnitine palmitoyltransferase I deficiency was demonstrated in cultured skin fibroblasts. Hypoglycemia was only found once in the neonatal period. Renal carnitine handling was normal except for a higher renal threshold for free carnitine. Mild, persistent metabolic acidosis was a constant feature, even during periods between metabolic decompensation. Evaluation of the renal acidification capacity showed a failure to acidify the urine during spontaneous acidosis but increased acid excretion and a normal decrease of urinary pH after acid loading. Also, a small difference between urine and blood PCO2 was found after bicarbonate administration. This acidification defect can best be explained as an abnormality in distal tubular H+ secretion: a rate-dependent distal tubular acidosis.off is speculated that long-chain acylcarnitines, substances that cannot be formed by carnitine palmitoyltransferase I-deficient patients, play an essential role in renal acid-base homeostasis.

Language of Publication

English

Unique Identifier

95183348

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MeSH Heading (Major)

Acidosis, Renal Tubular|BL/*EN; Carnitine|*BL; Carnitine O-Palmitoyltransferase|*DF; Reye Syndrome|BL/*EN

MeSH Heading

Biological Transport|PH; Case Report; Comparative Study; Female; Human; Hydrogen-Ion Concentration; Infant, Newborn; Kidney Function Tests; Protons; Secretory Rate|PH; Sodium Bicarbonate|DU/ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES

ISSN

0031-3998

Country of Publication

UNITED STATES

Record 35 from database: MEDLINE
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Title

Interactive regulation of the pyruvate dehydrogenase complex and the carnitine palmitoyltransferase system.

Author

Sugden MC; Holness MJ

Address

Department of Biochemistry (Basic Medical Sciences), Queen Mary and Westfield College, University of London, U.K.

Source

FASEB J, 1994 Jan, 8:1, 54-61

Abstract

The review examines the mechanisms regulating the activities of the two key enzymes determining rates of glucose and fatty acid oxidation, i.e., the pyruvate dehydrogenase (PDH) complex and the carnitine palmitoyltransferase (CPT) system. The review also evaluates the regulatory importance of gene expression in the control of tissue fuel selection within the context of substrate competition between glucose and fatty acids. It identifies a strong indirect input of nutrient-gene interactions in the control of pyruvate oxidation through the regulated provision of pyruvate as a substrate for PDH and as an inhibitor of PDH kinase. Nutrient-gene interactions are also identified in relation to the regulation of CPT I activity by malonyl-CoA (inhibitor) and by the provision of long-chain acyl-CoA (substrate/activator), the latter via the hydrolysis of plasma or tissue triacylglycerol (by lipoprotein lipase and hormone-sensitive lipase, respectively). We discuss how such regulation is reinforced by long-term modulation of PDH kinase-specific activity and CPT I maximal activity. We also explore the role of mechanisms operating at the levels of the PDH complex and the CPT system that act to promote and accelerate a switch in fuel utilization once a committed change in nutrient supply has been established. In particular, we discuss the regulatory influences exerted by altered sensitivities of PDH kinase to inhibition by pyruvate and CPT I to inhibition by malonyl-CoA, respectively.

Language of Publication

English

Unique Identifier

94131216

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MeSH Heading (Major)

Carnitine O-Palmitoyltransferase|GE/*ME; Nutrition|*PH; Pyruvate Dehydrogenase Complex|GE/*ME

MeSH Heading

Animal; Gene Expression Regulation; Human; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0892-6638

Country of Publication

UNITED STATES

Record 36 from database: MEDLINE
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Title

Molecular mechanism of acute ammonia toxicity and of its prevention by L-carnitine.

Author

Felipo V; Kosenko E; Miñana MD; Marcaida G; Grisolía S

Address

Instituto de Investigaciones CitolÆogicas, FundaciÆon Valenciana de Investigaciones BiomÆedicas, Valencia, Spain.

Source

Adv Exp Med Biol, 1994, 368:, 65-77

Abstract

In summary, we propose that acute ammonia intoxication leads to increased extracellular concentration of glutamate in brain and results in activation of the NMDA receptor. Activation of this receptor mediates ATP depletion and ammonia toxicity since blocking the NMDA receptor with MK-801 prevents both phenomena. Ammonia-induced metabolic alterations (in glycogen, glucose, pyruvate, lactate, glutamine, glutamate, etc) are not prevented by MK-801 and, therefore, it seems that they do not play a direct role in ammonia-induced ATP depletion nor in the molecular mechanism of acute ammonia toxicity. The above results suggest that ammonia-induced ATP depletion is due to activation of Na+/K(+)-ATPase, which, in turn, is a consequence of decreased phosphorylation by protein kinase C. This can be due to decreased activity of PKC or to increased activity of a protein phosphatase. We also show that L-carnitine prevents glutamate toxicity in primary neuronal cultures. The results shown indicate that carnitine increases the affinity of glutamate for the quisqualate type (including metabotropic) of glutamate receptors. Also, blocking the metabotropic receptor with AP-3 prevents the protective effect of L-carnitine, indicating that activation of this receptor mediates the protective effect of carnitine. We suggest that the protective effect of carnitine against acute ammonia toxicity in animals is due to the protection against glutamate neurotoxicity according to the above mechanisms.

Language of Publication

English

Unique Identifier

95259576

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MeSH Heading (Major)

Ammonia|AI/*TO; Carnitine|*PD

MeSH Heading

Animal; Brain Chemistry|DE/PH; Human; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0065-2598

Country of Publication

UNITED STATES

Record 37 from database: MEDLINE
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Title

L-Carnitine: therapeutic applications of a conditionally-essential amino acid.

Author

Kelly GS

Address

 

Source

Altern Med Rev, 1998 Oct, 3:5, 345-60

Abstract

A trimethylated amino acid roughly similar in structure to choline, carnitine is a cofactor required for transformation of free long-chain fatty acids into acylcarnitines, and for their subsequent transport into the mitochondrial matrix, where they undergo beta-oxidation for cellular energy production. Mitochondrial fatty acid oxidation is the primary fuel source in heart and skeletal muscle, pointing to the relative importance of this nutrient for proper function in these tissues. Although L-carnitine deficiency is an infrequent problem in a healthy, well-nourished population consuming adequate protein, many individuals within the population appear to be somewhere along a continuum, characterized by mild deficiency at one extreme, and tissue pathology at the other. Conditions which seem to benefit from exogenous supplementation of L-carnitine include anorexia, chronic fatigue, coronary vascular disease, diphtheria, hypoglycemia, male infertility, muscular myopathies, and Rett syndrome. In addition, preterm infants, dialysis patients, and HIV+ individuals seem to be prone to a deficiency of L-carnitine, and benefit from supplementation. Although available data on L-carnitine as an ergogenic aid is not compelling, under some experimental conditions pretreatment has favored aerobic processes and resulted in improved endurance performance.

Language of Publication

English

Unique Identifier

99021822

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MeSH Heading (Major)

Carnitine|DF/PK/*TU

MeSH Heading

Child; Drug Interactions; Female; Human; Male; Pregnancy

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1089-5159

Country of Publication

UNITED STATES

Record 38 from database: MEDLINE
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Title

Carnitine metabolism and its regulation in microorganisms and mammals.

Author

Rebouche CJ; Seim H

Address

Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242, USA. charles-rebouche@uiowa.edu

Source

Annu Rev Nutr, 1998, 18:, 39-61

Abstract

In procaryotes, L-carnitine may be used as both a carbon and nitrogen source for aerobic growth, or the carbon chain may be used selectively following cleavage trimethylamine. Under anaerobic conditions and in the absence of preferred substrates, some bacteria use carnitine, via crotonobetaine, as an electron acceptor. Formation of trimethylamine and lambda-butyrobetaine (from reduction of crotonobetaine) from L-carnitine by enteric bacteria has been demonstrated in rats and humans. Carnitine is not degraded by enzymes of eukaryotic origin. In higher organisms, carnitine has specific functions in intermediary metabolism. Concentrations of carnitine and its esters in cells of eukaryotes are rigorously maintained to provide optimal function. Carnitine homeostasis in mammals is preserved by a modest rate of endogenous synthesis, absorption from dietary sources, efficient reabsorption, and mechanisms present in most tissues that establish and maintain substantial concentration gradients between intracellular and extracellular carnitine pools.

Language of Publication

English

Unique Identifier

98371491

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MeSH Heading (Major)

Bacteria|*ME; Carnitine|AD/CH/*ME/PH

MeSH Heading

Animal; Diet; Homeostasis; Human; Kidney|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0199-9885

Country of Publication

UNITED STATES

Record 39 from database: MEDLINE
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Title

Genetic disorders of carnitine metabolism and their nutritional management.

Author

Kerner J; Hoppel C

Address

Department of Veteran Affairs Medical Center, Department of Nutrition, Cleveland, USA.

Source

Annu Rev Nutr, 1998, 18:, 179-206

Abstract

Carnitine functions as a substrate for a family of enzymes, carnitine acyltransferases, involved in acyl-coenzyme A metabolism and as a carrier for long-chain fatty acids into mitochondria. Carnitine biosynthesis and/or dietary carnitine fulfill the body's requirement for carnitine. To date, a genetic disorder of carnitine biosynthesis has not been described. A genetic defect in the high-affinity plasma membrane carnitine-carrier(in) leads to renal carnitine wasting and primary carnitine deficiency. Myopathic carnitine deficiency could be due to an increase in efflux moderated by the carnitine-carrier(out). Defects in the carnitine transport system for fatty acids in mitochondria have been described and are being examined at the molecular and pathophysiological levels. the nutritional management of these disorders includes a high-carbohydrate, low-fat diet and avoidance of those events that promote fatty acid oxidation, such as fasting, prolonged exercise, and cold. Large-dose carnitine treatment is effective in systemic carnitine deficiency.

Language of Publication

English

Unique Identifier

98371496

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MeSH Heading (Major)

Carnitine|*DF/*ME; Metabolism, Inborn Errors|*DH; Nutrition|*

MeSH Heading

Animal; Diet, Fat-Restricted; Dietary Carbohydrates|AD; Fatty Acids|ME; Human; Mitochondria|ME; Oxidation-Reduction; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0199-9885

Country of Publication

UNITED STATES

Record 40 from database: MEDLINE
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Title

Carnitine and cardiac interstitium.

Author

Hülsmann WC; Peschechera A; Arrigoni Martelli E

Address

Thoraxcenter, Erasmus University, Rotterdam, The Netherlands.

Source

Cardioscience, 1994 Jun, 5:2, 67-72

Abstract

An important part of (acyl)carnitine may be stored in interstitial spaces and the external surface of adjacent cells. A high concentration of carnitine in the direct vicinity of cells may enhance the synthesis and export of long-chain acylcarnitine. Long-chain acylcoenzyme A, from which long-chain acyl carnitine is formed, cannot penetrate intact cell membranes. During hypoperfusion or ischemia, when long-chain acylcoenzyme A accumulates due to hampered fatty acid oxidation, there is an increased formation of long-chain acyl carnitine which diffuses into the interstitium and adjacent vascular endothelial cells. Due to its lipophilic nature and net positive charge (limitation of carboxyl-group dissociation in ischemic acidosis), long-chain acyl carnitine may decrease the affinity of Ca2+ to the cell surface and prevent Ca2+ overload of cells. The advantage of carnitine over many other cationic amphiphiles in the protection of areas of ischemia is that long-chain acyl carnitine is formed and stored only in ischemic areas.

Language of Publication

English

Unique Identifier

95002604

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MeSH Heading (Major)

Carnitine|BI/*ME; Myocardial Ischemia|*PP; Myocardium|CY/*ME

MeSH Heading

Animal; Calcium Channels|ME; Heart|PH; Human; Oxygen|ME; Rats

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1015-5007

Country of Publication

ITALY

Record 41 from database: MEDLINE
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Title

Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake.

Author

Stanley CA; DeLeeuw S; Coates PM; Vianey Liaud C; Divry P; Bonnefont JP; Saudubray JM; Haymond M; Trefz FK; Breningstall GN; et al

Address

Division of Endocrinology/Diabetes, Children's Hospital of Philadelphia, PA 19104.

Source

Ann Neurol, 1991 Nov, 30:5, 709-16

Abstract

A defect in intracellular uptake of carnitine has been identified in patients with severe carnitine deficiency. To define the clinical manifestations of this disorder, the presenting features of 15 affected infants and children were examined. Progressive cardiomyopathy, with or without chronic muscle weakness, was the most common presentation (median age of onset, 3 years). Other patients presented with episodes of fasting hypoglycemia during the first 2 years of life before cardiomyopathy had become apparent. A defect in carnitine uptake was demonstrable in fibroblasts and leukocytes from patients. The defect also appears to be expressed in muscle and kidney. Concentrations of plasma carnitine and rates of carnitine uptake in parents were intermediate between affected patients and normal control subjects, consistent with recessive inheritance. Early recognition and treatment with high doses of oral carnitine may be life-saving in this disorder of fatty acid oxidation.

Language of Publication

English

Unique Identifier

92109441

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MeSH Heading (Major)

Carnitine|*PK/TU; Coma|DT/GE/*ME; Lipid Metabolism, Inborn Errors|DT/GE/*ME; Myocardial Diseases|DT/GE/*ME

MeSH Heading

Biological Transport; Case Report; Cells, Cultured; Child; Child, Preschool; Fatty Acids|ME; Female; Fibroblasts|ME; Genes, Recessive; Human; Hypoglycemia|GE/ME; Kidney|ME; Leukocytes|ME; Male; Mitochondria|ME; Muscles|ME; Oxidation-Reduction; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES

ISSN

0364-5134

Country of Publication

UNITED STATES

Record 42 from database: MEDLINE
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Title

Ascorbic acid and carnitine biosynthesis.

Author

Rebouche CJ

Address

Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242.

Source

Am J Clin Nutr, 1991 Dec, 54:6 Suppl, 1147S-1152S

Abstract

It has been suggested that early features of scurvy (fatigue and weakness) may be attributed to carnitine deficiency. Ascorbate is a cofactor for two alpha-ketoglutarate-requiring dioxygenase reactions (epsilon-N-trimethyllysine hydroxylase and gamma-butyrobetaine hydroxylase) in the pathway of carnitine biosynthesis. Carnitine concentrations are variably low in some tissues of scorbutic guinea pigs. Ascorbic acid deficiency in guinea pigs resulted in decreased activity of hepatic gamma-butyrobetaine hydroxylase and renal but not hepatic epsilon-N-trimethyllsine hydroxylase when exogenous substrates were provided. It remains unclear whether vitamin C deficiency has a significant impact on the overall rate of carnitine synthesis from endogenous substrates. Nevertheless, results of studies of enzyme preparations and perfused liver in vitro and of scorbutic guinea pigs in vivo provide compelling evidence for participation of ascorbic acid in carnitine biosynthesis.

Language of Publication

English

Unique Identifier

92074394

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MeSH Heading (Major)

Ascorbic Acid|*PD; Carnitine|*BI/BL

MeSH Heading

Animal; Ascorbic Acid Deficiency|BL; Human; Hydroxylases|ME; Hydroxylation

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-9165

Country of Publication

UNITED STATES

Record 43 from database: MEDLINE
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Title

A role for carnitine in medium-chain fatty acid metabolism?

Address

 

Source

Nutr Rev, 1991 Aug, 49:8, 243-5

Abstract

Medium-chain triglycerides do not require carnitine for mitochondrial transport. However, new data suggest that carnitine may play a role in their utilization.

Language of Publication

English

Unique Identifier

92066247

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MeSH Heading (Major)

Carnitine|*PH; Fatty Acids|*ME

MeSH Heading

Human; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0029-6643

Country of Publication

UNITED STATES

Record 44 from database: MEDLINE
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Title

Carnitine deficiency-induced cardiomyopathy.

Author

Paulson DJ

Address

Department of Physiology, Midwestern University, Downers Grove, Illinois 60515, USA.

Source

Mol Cell Biochem, 1998 Mar, 180:1-2, 33-41

Abstract

The results of clinical and animal studies suggest that a short term period of moderate secondary carnitine deficiency, in and of itself, does not have a major effect on the cardiac contractile function, although substrate oxidation may be altered. However, with longer durations of carnitine deficiency, alterations occur within the heart that may result in impaired contractile performance, particularly at high workloads. At this point, the mechanisms responsible for the cardiac depression are uncertain. We hypothesize that the alterations in substrate metabolism produced by the carnitine deficient state results in inadequate ATP production under high workload conditions which result in impaired cardiac contractile performance. Carnitine deficiency may also induce a number of changes in gene expression of key enzymes required for normal cardiac contractile function and metabolism.

Language of Publication

English

Unique Identifier

98206705

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MeSH Heading (Major)

Carnitine|*DF; Myocardial Diseases|*ET; Vitamin B Deficiency|*CO

MeSH Heading

Animal; Disease Models, Animal; Human; Kinetics; Models, Biological; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0300-8177

Country of Publication

NETHERLANDS

Record 45 from database: MEDLINE
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Title

Differential regulation in the heart of mitochondrial carnitine palmitoyltransferase-I muscle and liver isoforms.

Author

Park EA; Cook GA

Address

Department of Pharmacology, College of Medicine, The University of Tennessee, Memphis-The Health Science Center, 38163, USA.

Source

Mol Cell Biochem, 1998 Mar, 180:1-2, 27-32

Abstract

Carnitine palmitoyltransferase-I (CPT-I) plays a crucial role in regulating cardiac fatty acid oxidation which provides the primary source of energy for cardiac muscle contraction. CPT-I catalyzes the transfer of long chain fatty acids into mitochondria and is recognized as the primary rate controlling step in fatty acid oxidation. Molecular cloning techniques have demonstrated that two CPT-I isoforms exist as genes encoding the 'muscle' and 'liver' enzymes. Regulation of fatty acid oxidation rates depends on both short-term regulation of enzyme activity and long-term regulation of enzyme synthesis. Most early investigations into metabolic control of fatty acid oxidation at the CPT-I step concentrated on the hepatic enzyme which can be inhibited by malonyl-CoA and can undergo dramatic amplification or reduction of its sensitivity to inhibition by malonyl-CoA. The muscle CPT-I is inherently more sensitive to malonyl-CoA inhibition but has not been found to undergo any alteration of its sensitivity. Short-term control of activity of muscle CPT-I is apparently regulated by malonyl-CoA concentration in response to fuel supply (glucose, lactate, pyruvate and ketone bodies). The liver isoform is the only CPT-I enzyme present in the mitochondria of liver, kidney, brain and most other tissues while muscle CPT-I is the sole isoform expressed in skeletal muscle as well as white and brown adipocytes. The heart is unique in that it contains both muscle and liver isoforms. Liver CPT-I is highly expressed in the fetal heart, but at birth its activity begins to decline whereas the muscle isoform, which is very low at birth, becomes the predominant enzyme during postnatal development. In this paper, the differential regulation of the two CPT-I isoforms at the protein and the gene level will be discussed.

Language of Publication

English

Unique Identifier

98206704

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MeSH Heading (Major)

Carnitine O-Palmitoyltransferase|GE/*ME; Isoenzymes|*ME; Liver|*EN; Mitochondria, Heart|*EN; Muscles|*EN

MeSH Heading

Amino Acid Sequence; Animal; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Human; Molecular Sequence Data

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0300-8177

Country of Publication

NETHERLANDS

Record 46 from database: MEDLINE
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Title

Propionyl-L-carnitine.

Author

Wiseman LR; Brogden RN

Address

Adis International Limited, Auckland, New Zealand.

Source

Drugs Aging, 1998 Mar, 12:3, 243-8; discussion 249-50

Abstract

Propionyl-L-carnitine stimulates energy production in ischaemic muscles by increasing citric acid cycle flux and stimulating pyruvate dehydrogenase activity. The free radical scavenging activity of the drug may also be beneficial. Propionyl-L-carnitine improves coagulative fibrinolytic homeostasis in vasal endothelium and positively affects blood viscosity. Improvements in maximum walking distance (MWD) correlated positively with increased mitochondrial oxidative adenosine triphosphate (ATP) synthesis in a study in patients with peripheral arterial disease. Oral propionyl-L-carnitine 1 to 3 g/day significantly improved mean MWD compared with placebo in patients with peripheral arterial obstructive disease (Fontaine Leriche stage II) in double-blind multicentre phase III studies (mean improvements ranged from 21 to 50% with placebo and from 33 to 73% with propionyl-L-carnitine). In one phase III study, propionyl-L-carnitine 1 to 3 g/day significantly improved mean MWD (measured by treadmill) compared with placebo (by 73 vs 46% after 24 weeks) in patients with intermittent claudication. Oral propionyl-L-carnitine therapy was associated with significant improvements in quality of life compared with placebo in patients with a baseline MWD < 250m. Propionyl-L-carnitine appears to be well tolerated, showing a similar incidence of adverse events to that reported in placebo recipients.

Language of Publication

English

Unique Identifier

98195507

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MeSH Heading (Major)

Arterial Occlusive Diseases|*DT; Cardiotonic Agents|PK/*TU; Carnitine|*AA/PK/TU

MeSH Heading

Aged; Clinical Trials; Human; Muscle, Skeletal|DE/ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1170-229X

Country of Publication

NEW ZEALAND

Record 47 from database: MEDLINE
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Title

Carnitine metabolism during exercise.

Author

Brass EP; Hiatt WR

Address

Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4981.

Source

Life Sci, 1994, 54:19, 1383-93

Abstract

Carnitine is an important cofactor for normal cellular metabolism. Optimal utilization of fuel substrates for ATP generation by skeletal muscle during exercise is dependent on adequate carnitine stores. During short periods of exercise the skeletal muscle carnitine pool is largely segregated from extracellular carnitine. In normal human subjects, only minimal changes in the muscle carnitine pool are observed during exercise at work loads below the lactate threshold. In contrast, at work-loads above the lactate threshold the muscle total carnitine is redistributed from carnitine to acetylcarnitine, with the acetylcarnitine content correlated with the muscle acetyl-CoA and lactate contents. In contrast, in patients with peripheral arterial disease, an accumulation of acylcarnitines is observed at all work loads. Patients with chronic renal failure who are on hemodialysis demonstrate a poor exercise capability which is correlated with a decrease in muscle carnitine content. Carnitine supplementation has been shown to improve exercise tolerance in both peripheral arterial disease and hemodialysis patients. Further work is needed to define the mechanism by which exogenous carnitine improves exercise performance in order to better define potential patient populations for therapy and to facilitate optimal dosing regimens.

Language of Publication

English

Unique Identifier

94247261

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MeSH Heading (Major)

Carnitine|*ME/PD; Exercise|*; Exertion|*; Muscles|DE/*ME; Vascular Diseases|*ME

MeSH Heading

Acetyl Coenzyme A|ME; Acetylcarnitine|ME; Adenosine Triphosphate|ME; Human; Lactates|ME; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0024-3205

Country of Publication

ENGLAND

Record 48 from database: MEDLINE
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Title

L-Carnitine moiety assay: an up-to-date reappraisal covering the commonest methods for various applications.

Author

Marzo A; Curti S

Address

I.P.A.S. S.A., Clinical Pharmacology Department, Ligornetto, Switzerland.

Source

J Chromatogr B Biomed Sci Appl, 1997 Nov, 702:1-2, 1-20

Abstract

L-Carnitine and its esters are typical endogenous substances. Their homeostatic equilibria are effectively controlled by various mechanisms which include rate-limiting enteral absorption, a multicomponent endogenous pool which is regulated acrding to a mammillary metabolism, an asymmetric body distribution and a saturable tubular reabsorption process leading to renal thresholds. In formal pharmacokinetic and metabolic investigations, the whole L-carnitine pool should be investigated, owing to the rapid interchange process between the various components of the pool. Free L-carnitine, as well as its acyl esters, must therefore be considered from an analytical viewpoint. L-Carnitine, acetyl-L-carnitine and total L-carnitine (the latter as an expression of the whole pool) can easily be assayed by enzyme or radioenzyme methods. Propionyl-L-carnitine and other esters containing fatty acids with more than three carbon atoms can be assayed using various HPLC approaches. Tandem mass spectrometry is another excellent approach to the assay of carnitine and its short-chain, medium-chain and long-chain esters. As L-carnitine contains a chiral carbon atom, the enantioselectivity of the assays is also considered in this review. Metabolites produced by enteral bacteria, namely tri-, di- and mono-methylamine, gamma-butyrobetaine, along with other systemic metabolites, namely trimethylamine N-oxide and N-nitroso dimethylamine, are very important in quantitative and toxicokinetic terms and require specific assay methods. This review covers the commonest methods of assaying carnitine and its esters, their impurities and pre-systemic and systemic metabolites and gives analytical details and information on their applications in pharmaceutics, biochemistry, pharmacokinetics and toxicokinetics.

Language of Publication

English

Unique Identifier

98109605

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MeSH Heading (Major)

Carnitine|*AN/CH/ME; Chromatography, Gas|*MT; Chromatography, High Pressure Liquid|*MT; Spectrum Analysis, Mass|*MT

MeSH Heading

Child, Preschool; Comparative Study; Esters; Female; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1387-2273

Country of Publication

NETHERLANDS

Record 49 from database: MEDLINE
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Title

Acetyl-L-carnitine and Alzheimer's disease: pharmacological considerations beyond the cholinergic sphere.

Author

Carta A; Calvani M; Bravi D; Bhuachalla SN

Address

Sigma-Tau Pharmaceuticals, Department of Scientific Affairs, Gaithersburg, Maryland 20878.

Source

Ann N Y Acad Sci, 1993 Sep, 695:, 324-6

Abstract

Since ALCAR and L-carnitine are "shuttles" of long chain fatty acids between the cytosol and the mitochondria to undergo beta-oxidation, they play an essential role in energy production and in clearing toxic accumulations of fatty acids in the mitochondria. ALCAR has been considered of potential use in senile dementia of the Alzheimer type (SDAT) because of its ability to serve as a precursor for acetylcholine. However, pharmacological studies with ALCAR in animals have demonstrated its facility to maximize energy production and promote cellular membrane stability, particularly its ability to restore membranal changes that are age-related. Since recent investigations have implicated abnormal energy processing leading to cell death, and severity-dependent membrane disruption in the pathology of Alzheimer's disease, we speculate that the beneficial effects associated with ALCAR administration in Alzheimer patients are due not only to its cholinergic properties, but also to its ability to support physiological cellular functioning at the mitochondrial level. This hypothetical mechanism of action is discussed with respect to compelling supportive animal studies and recent observations of significant decrease of carnitine acetyltransferase (the catalyst of L-carnitine acylation to acetyl-L-carnitine) in autopsied Alzheimer brains.

Language of Publication

English

Unique Identifier

94057854

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MeSH Heading (Major)

Acetylcarnitine|PD/*TU; Alzheimer Disease|*DT/EN/PA

MeSH Heading

Aging|ME; Animal; Brain|EN/PA; Carnitine O-Acetyltransferase|ME; Human; Mitochondria|DE/ME; Support, Non-U.S. Gov't; Transcription, Genetic|DE

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0077-8923

Country of Publication

UNITED STATES

Record 50 from database: MEDLINE
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Title

Regulation of the long-chain carnitine acyltransferases.

Author

Brady PS; Ramsay RR; Brady LJ

Address

Department of Food Science and Nutrition, University of Minnesota, St. Paul 55108.

Source

FASEB J, 1993 Aug, 7:11, 1039-44

Abstract

Long-chain carnitine acyltransferases are a family of enzymes found in mitochondria, peroxisomes, and endoplasmic reticulum that catalyze the exchange of carnitine for coenzyme A in the fatty acyl-CoA. Conversion of the fatty acyl-CoA to fatty acylcarnitine renders the fatty acid more permeable to the various cellular membranes. The mitochondrial carnitine palmitoyltransferases are considered important in the regulation of mitochondrial beta-oxidation of long-chain fatty acids. However, palmitoylcarnitine produced by peroxisomal carnitine octanoyltransferase or by microsomal carnitine palmitoyltransferase is not different from that produced by the mitochondrial enzyme. Therefore, for there to be control of fatty acid oxidation by the long-chain carnitine acyltransferases, there would have to be some mechanism to coordinately regulate these varied enzymes. The first system of regulation involves inhibition by malonyl-CoA, an intermediate in the synthesis of fatty acids. Malonyl-CoA inhibits long-chain carnitine acyltransferase activity by all three enzymes at similar concentrations in the physiological range. In addition, the mitochondrial and peroxisomal enzymes are known to be regulated at the level of mRNA transcription by a number of shared factors. Although the microsomal enzyme is less well studied, there does, indeed, appear to be a pattern of coordinate regulation for this system.

Language of Publication

English

Unique Identifier

93380589

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MeSH Heading (Major)

Carnitine Acyltransferases|*PH

MeSH Heading

Animal; Carnitine O-Palmitoyltransferase|PH; Fatty Acids|ME; Human; Malonyl Coenzyme A|PH; Mitochondria|EN; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0892-6638

Country of Publication

UNITED STATES