l Carnitine

Record 1 from database: MEDLINE
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10

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

Return To Top
Return To Menu Position #10

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
Return To Top
Return To Menu Position #10
Return To Menu Position #20

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

Return To Top
Return To Menu Position #10
Return To Menu Position #20

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
Return To Top
Return To Menu Position #10
Return To Menu Position #20

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

Return To Top
Return To Menu Position #10
Return To Menu Position #20

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
Return To Top
Return To Menu Position #10
Return To Menu Position #20

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

Return To Top
Return To Menu Position #10
Return To Menu Position #20

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
Return To Top
Return To Menu Position #20

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

Return To Top
Return To Menu Position #20

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
Return To Top
Return To Menu Position #20

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

Return To Top
Return To Menu Position #20

MeSH Heading (Major)

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

MeSH