Choline

Record 1 from database: MEDLINE
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Title

Brain choline has a typical precursor profile.

Author

Löffelholz K

Address

Department of Pharmacology, University of Mainz, Germany.

Source

J Physiol Paris, 1998 Jun, 92:3-4, 235-9

Abstract

Choline is product and precursor to both acetylcholine and membrane phospholipids, and, in the brain, is ultimately provided by the circulation. The brain is protected from excess choline and choline deprivation by a refined system of homeostatic mechanisms that maintain a level of extracellular choline that, for its role as precursor, meets saturation criteria under normal conditions. The kinetic and activity profiles of choline are typical for a biosynthetic precursor.

Language of Publication

English

Unique Identifier

99006244

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MeSH Heading (Major)

Acetylcholine|*BI; Brain|*ME; Choline|*ME; Phospholipids|*BI

MeSH Heading

Animal; Homeostasis; Human; Kinetics; Support, Non-U.S. Gov't; Synapses|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0928-4257

Country of Publication

FRANCE

Record 2 from database: MEDLINE
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Title

Dietary Reference Intakes: the new basis for recommendations for calcium and related nutrients, B vitamins, and choline.

Author

Yates AA; Schlicker SA; Suitor CW

Address

Food and Nutrition Board, Institute of Medicine, National Academy of Sciences, Washington, DC 20418, USA.

Source

J Am Diet Assoc, 1998 Jun, 98:6, 699-706

Abstract

Dietary Reference Intakes (DRIs) represent the new approach adopted by the Food and Nutrition Board to providing quantitative estimates of nutrient intakes for use in a variety of settings, replacing and expanding on the past 50 years of periodic updates and revisions of the Recommended Dietary Allowances (RDAs). The DRI activity is a comprehensive effort undertaken to include current concepts about the role of nutrients and food components in long-term health, going beyond deficiency diseases. The DRIs consist of 4 reference intakes: the RDA, which is to be used as a goal for the individual; the Tolerable Upper Intake Level (UL), which is given to assist in advising individuals what levels of intake may result in adverse effects if habitually exceeded; the Estimated Average Requirement (EAR), the intake level at which the data indicate that the needs for 50% of those consuming it will not be met; and the Adequate Intake (AI), a level judged by the experts developing the reference intakes to meet the needs of all individuals in a group, but which is based on much less data and substantially more judgment than that used in establishing an EAR and subsequently the RDA. When an RDA cannot be set, an AI is given. Both are to be used as goals for an individual. Two reports have been issued providing DRIs for nutrients and food components reviewed to date: these include calcium and its related nutrients: phosphorus, magnesium, vitamin D, and fluoride; and most recently, folate, the B vitamins, and choline. The approaches used to determine the DRIs, the reference values themselves, and the plans for future nutrients and food components are discussed.

Language of Publication

English

Unique Identifier

98291100

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MeSH Heading (Major)

Guidelines|*; National Academy of Sciences (U.S.)|*; Nutrition Policy|*

MeSH Heading

Calcium, Dietary|AD; Choline|AD; Human; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; United States; Vitamin B Complex|AD

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-8223

Country of Publication

UNITED STATES

Record 3 from database: MEDLINE
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Title

Choline: essential for brain development and function.

Author

Zeisel SH

Address

Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina, Chapel Hill, USA.

Source

Adv Pediatr, 1997, 44:, 263-95

Abstract

Pregnancy and lactation are periods when maternal reserves of choline are depleted. At the same time, the availability of choline for normal development of brain is critical. Variations in choline intake by mothers influence memory performance in their offspring. The mechanisms for this potent effect of choline are not yet elucidated but may involve changes in acetylcholine synthesis, transmembrane signal transduction, or regulation of apoptosis. These observations are important for the obstetrician and pediatrician as they consider the ideal dietary intake for mothers and their children.

Language of Publication

English

Unique Identifier

97410924

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MeSH Heading (Major)

Brain|EM/*GD; Choline|*PH; Choline Deficiency|*PP; Pregnancy Complications|*PP

MeSH Heading

Acetylcholine|ME; Animal; Apoptosis|PH; Female; Human; Infant, Newborn; Lactation|ME; Pregnancy; Rats; Signal Transduction|PH; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0065-3101

Country of Publication

UNITED STATES

Record 4 from database: MEDLINE
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Title

Essential nature of choline with implications for total parenteral nutrition.

Author

Shronts EP

Address

Department of Surgery, University of Minnesota, Minneapolis 55455, USA.

Source

J Am Diet Assoc, 1997 Jun, 97:6, 639-46, 649; quiz 647-8

Abstract

Choline is known to be important in many metabolic pathways; at this time, however, it is not considered an essential nutrient for human beings. Current evidence strongly suggests that choline is "conditionally essential," particularly for patients receiving total parenteral nutrition (TPN). Studies in patients receiving long-term TPN have shown that low levels of plasma choline are common and can be associated with hepatic steatosis. Treatment of these patients with oral administration of choline improved plasma levels and decreased hepatic fat content; however, oral choline supplements are associated with poor compliance. More recently, investigators have evaluated intravenous administration of choline as a treatment for TPN-associated hepatic steatosis in patients with documented subnormal plasma free-choline levels. Initial results indicate that intravenous administration of choline may be an effective treatment for TPN-associated hepatic dysfunction.

Language of Publication

English

Unique Identifier

97326505

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MeSH Heading (Major)

Choline|AD/*ME/TU; Fatty Liver|BL/DT/*ET; Parenteral Nutrition, Total|*AE

MeSH Heading

Administration, Oral; Clinical Trials; Dietetics|ED; Dose-Response Relationship, Drug; Human; Injections, Intravenous; Lipids|AN; Liver|CH/ME/PP; Questionnaires; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-8223

Country of Publication

UNITED STATES

Record 5 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 6 from database: MEDLINE
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Title

High affinity choline transporter status in Alzheimer's disease tissue from rapid autopsy.

Author

Bissette G; Seidler FJ; Nemeroff CB; Slotkin TA

Address

Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA.

Source

Ann N Y Acad Sci, 1996 Jan, 777:, 197-204

Abstract

The degeneration of nucleus basalis cholinergic neurons in Alzheimers disease (AD) has led to therapies that attempt to increase the synaptic availability of acetylcholine in the remaining cholinergic nerve terminals and to thereby reverse or slow the progressive dementia accompanying the disease process. The inadequacy of current choline-replacement therapies suggests that utilization of choline may be disordered and the rate-limiting step in acetylcholine synthesis, the high affinity choline transporter, may be involved. An adequate test of this hypothesis requires the use of fresh, unfrozen tissue, as the transporter activity declines rapidly after death. Using tissue acquired within two hours of death, the activity of the high affinity choline transporter was shown to be increased in cortical brain regions from AD patients compared to non-AD controls. Further studies using frozen tissues with similar short postmortem acquisition times, revealed the expression of the high affinity uptake transporter to be increased in AD cortex as well. When the ratio of regional uptake activity or expression to the regional level of choline acetyltransferase was calculated, the increase in choline transporter activity and expression was clearly statistically significant. Further statistical significance in the choline transporter activity of the AD group was achieved when the putamen, a region without marked pathology in AD, was used as an internal standard to control for agonal state differences in the individual patients contributing tissue to this study. These increases in choline transporter expression and activity in AD indicate disordered regulation of this rate-limiting component of acetylcholine synthesis above and beyond that required to compensate for the reduced cholinergic synaptic availability in AD.

Language of Publication

English

Unique Identifier

96187018

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MeSH Heading (Major)

Alzheimer Disease|*ME; Brain|*ME; Carrier Proteins|*ME

MeSH Heading

Binding, Competitive; Choline|ME; Choline O-Acetyltransferase|ME; Hemicholinium 3|ME; Human; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0077-8923

Country of Publication

UNITED STATES

Record 7 from database: MEDLINE
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Title

Choline. A nutrient that is involved in the regulation of cell proliferation, cell death, and cell transformation.

Author

Zeisel SH

Address

Department of Nutrition, University of North Carolina at Chapel Hill, School of Public Health 27599-7400, USA.

Source

Adv Exp Med Biol, 1996, 399:, 131-41

Abstract

Choline deficiency causes hepatocyte proliferation, apoptosis and transformation. Thus, it is an excellent model in which to study the molecular mechanisms underlying these processes. Several interesting questions can be addressed. What is the first event that begins the cells on the path towards transformation? Is it triggered by some autocrine factor produced in choline depleted cells? Does it involve alteration of DNA structure with subsequent apoptosis, compensatory cell proliferation, and enhanced survival of preneoplastic cells? Is there a specific choline deficiency signal which triggers apoptosis, with subsequent compensatory cell proliferation in a methyl-deficient environment causing hypomethylation of DNA? Does this result in abnormal transcription of genes with resulting transformation? Or is the activation of PKC the first event? PKC-mediated cell proliferation might then be balanced by down regulation of growth factor response, withdrawal of which causes apoptosis. The ensuing high rate of cell turnover might result in the survival and replication of preneoplastic cells. Multiple alternative variations of these questions exist. Whatever the critical first event is, our models also allow us to ask about molecular differences between cells that pass through these early events and those that do not. At first glance, choline deficiency may seem to be an artificial situation that might rarely occur in nature. However, the answers to some of the above questions will help us to understand how changes in gene expression and the signaling pathways that are fundamental for many cell functions, might be involved in liver cell proliferation, death and transformation.

Language of Publication

English

Unique Identifier

97091887

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MeSH Heading (Major)

Cell Death|*PH; Cell Division|*PH; Cell Transformation, Neoplastic|*; Choline|*PH; Choline Deficiency|*CO

MeSH Heading

Animal; Cell Line; Human; Models, Biological; Neoplasms|ET; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0065-2598

Country of Publication

UNITED STATES

Record 8 from database: MEDLINE
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Title

Choline: an important nutrient in brain development, liver function and carcinogenesis.

Author

Zeisel SH

Address

Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill 27599.

Source

J Am Coll Nutr, 1992 Oct, 11:5, 473-81

Abstract

Choline is required to make certain phospholipids which are essential components of all membranes. It is a precursor for biosynthesis of the neurotransmitter acetylcholine and also is an important source of labile methyl groups. Much attention has been given to the effect of supplemental choline upon brain function, i.e., enhancement of acetylcholine synthesis and release. In addition, choline supplements administered to rats in utero or shortly after birth permanently after brain function. The mechanisms for this effect is unknown and under investigation at this time. Healthy humans fed diets deficient in choline, and humans fed parenterally have decreased plasma choline concentrations and develop liver dysfunction that is similar to that seen in choline-deficient animals. In experimental animals, fatty liver occurs in choline deficiency because phosphatidylcholine synthesis is required for very low-density lipoprotein secretion. This accumulation of lipids in liver may explain why choline-deficient rats spontaneously develop hepatocarcinoma. We found that choline deficiency was associated with the accumulation of 1,2-diacylglycerol, an activator of protein kinase C. Several lines of evidence indicate that cancers might develop secondary to abnormalities in protein kinase C-mediated signal transduction.

Language of Publication

English

Unique Identifier

93085083

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MeSH Heading (Major)

Brain|*DE/GD; Choline|BL/ME/*PD; Liver|*DE/PH; Neoplasms|*PC

MeSH Heading

Alanine Transaminase|BL; Animal; Diet; Human; Rats; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0731-5724

Country of Publication

UNITED STATES

Record 9 from database: MEDLINE
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Title

CDP-choline: pharmacological and clinical review.

Author

Secades JJ; Frontera G

Address

F.I.S.A. Medical Department, Barcelona.

Source

Methods Find Exp Clin Pharmacol, 1995 Oct, 17 Suppl B:, 2-54

Abstract

Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS. Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models. CDP-choline is a safe drug, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this drug may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology. In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome. In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients. The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution. Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.

Language of Publication

English

Unique Identifier

96288310

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MeSH Heading (Major)

Cytidine Diphosphate Choline|*PD/PK/*TU; Nootropic Agents|*PD/PK/*TU

MeSH Heading

Animal; Biological Availability; Cerebrovascular Disorders|DT; Dementia|DT; Head Injuries|DT; Human; Parkinson Disease|DT; Tissue Distribution

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0379-0355

Country of Publication

SPAIN

Record 10 from database: MEDLINE
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Title

Choline: a conditionally essential nutrient for humans.

Address

 

Source

Nutr Rev, 1992 Apr, 50:4 ( Pt 1), 112-4

Abstract

Tissue concentrations of choline decreased significantly while serum alanine aminotransferase activity, a marker of liver injury, increased sharply (by 50%) when healthy young adult men received a choline-free semisynthetic diet for three weeks. This study suggests that choline is an essential nutrient for humans when excess methionine and folate are not available in the diet.

Language of Publication

English

Unique Identifier

92310714

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MeSH Heading (Major)

Choline|*PH; Choline Deficiency|*PP; Liver|*PP

MeSH Heading

Alanine Transaminase|BL; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0029-6643

Country of Publication

UNITED STATES

Record 11 from database: MEDLINE
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Title

Overexpression of choline acetyltransferase reconstitutes discrete acetylcholine release in some but not all synapse formation-defective neuroblastoma cells.

Author

Zhong ZG; Misawa H; Furuya S; Kimura Y; Noda M; Yokoyama S; Higashida H

Address

Department of Biophysics, Kanazawa University School of Medicine, Japan.

Source

J Physiol Paris, 1995, 89:3, 137-45

Abstract

Secretion of acetylcholine (ACh) in neuroblastoma cells overexpressing choline acetyltransferase (ChAT) was examined. With transient transfection of ChAT cDNA, neuroblastoma cells, which have no endogenous ChAT and either adhere to myotubes or not, failed to form functional synapses, and thus no evidence for release of ACh was detected. Stable neuroblastoma cell lines overexpressing ChAT accumulated ACh inside the cell, and slowly released ACh to the outside of the cell in a calcium-independent fashion. However, after co-culturing them with rat muscle cells, these transformed cells adhered to myotubes and ACh was secreted in a discrete fashion into the synaptic cleft efficiently in some neuroblastoma cell lines but rather inefficiently in another cell line. The results show that the latent secretion machinery of ChAT overexpressing neuroblastoma cells either is competent or possess defect(s) in ACh release.

Language of Publication

English

Unique Identifier

96030107

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MeSH Heading (Major)

Acetylcholine|*ME; Choline O-Acetyltransferase|GE/*ME; Neuroblastoma|PA/*PP; Synapses|*PH

MeSH Heading

Animal; Coculture; DNA, Complementary; Human; Muscles|CY; Transfection; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0928-4257

Country of Publication

FRANCE

Record 12 from database: MEDLINE
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Title

Cholinergic synapses in the central nervous system: studies of the immunocytochemical localization of choline acetyltransferase.

Author

Houser CR

Address

Neurology Service, Veterans Administration Medical Center, West Los Angeles, California 90073.

Source

J Electron Microsc Tech, 1990 May, 15:1, 2-19

Abstract

Cholinergic synapses can be identified in immunocytochemical preparations by the use of monoclonal antibodies and specific antisera to choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine (ACh) and a specific marker for cholinergic neurons. Electron microscopic studies demonstrate that the fibers and varicosities observed in light microscopic preparations of many brain regions are small-diameter unmyelinated axons and vesicle-containing boutons. The labeled boutons generally contain clear vesicles and one or more mitochondrial profiles. Many of these boutons form synaptic contacts, and the synapses are frequently of the symmetric type, displaying thin postsynaptic densities and relatively short contact zones. However, ChAT-labeled synapses with asymmetric junctions are also observed, and their frequency varies among different brain regions. Unlabeled dendritic shafts are the most common postsynaptic elements in virtually all regions examined although other neuronal elements, including dendritic spines and neuronal somata, also receive some cholinergic innervation. ChAT-labeled boutons form synaptic contacts with several different types of unlabeled neurons within the same brain region. Such findings are consistent with a generally diffuse pattern of cholinergic innervation in many parts of the central nervous system. Despite many similarities in the characteristics of ChAT-labeled synapses, there appears to be some heterogeneity in the cholinergic innervation within as well as among brain regions. Differences are observed in the sizes of ChAT-immunoreactive boutons, the types of synaptic contacts, and the predominant postsynaptic elements. Thus, the cholinergic system presents interesting challenges for future studies of the morphological organization and related function of cholinergic synapses.

Language of Publication

English

Unique Identifier

90250513

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MeSH Heading (Major)

Central Nervous System|*UL; Choline O-Acetyltransferase|*AN; Cholinergic Fibers|*UL; Synapses|*UL

MeSH Heading

Animal; Cerebral Cortex|UL; Corpus Striatum|UL; Hippocampus|UL; Human; Immunohistochemistry; Microscopy, Electron; Spinal Cord|UL; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Thalamus|UL

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0741-0581

Country of Publication

UNITED STATES

Record 13 from database: MEDLINE
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Title

Choline metabolism as a basis for the selective vulnerability of cholinergic neurons.

Author

Wurtman RJ

Address

Dept of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.

Source

Trends Neurosci, 1992 Apr, 15:4, 117-22

Abstract

The unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.

Language of Publication

English

Unique Identifier

92263540

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MeSH Heading (Major)

Choline|*ME; Cholinergic Fibers|DE/*ME

MeSH Heading

Animal; Human; Nervous System Diseases|ME/PP

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0166-2236

Country of Publication

ENGLAND

Record 14 from database: MEDLINE
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Title

Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury.

Author

DOrlando KJ; Sandage BW Jr

Address

Interneuron Pharmaceuticals Inc., Lexington, MA 02173, USA.

Source

Neurol Res, 1995 Aug, 17:4, 281-4

Abstract

Citicoline is approved in Europe and Japan for use in stroke, head trauma and other neurological disorders. It is presently being evaluated in phase II/III stroke trials in the United States. Exogenous administration of CDP-choline provides both choline and cytidine which access the brain and serve as substrates for the synthesis of phosphatidylcholine, a primary neuronal membrane component; the choline also enhances brain acetylcholine synthesis. Membrane repair and regeneration is necessary for recovery from stroke. Furthermore, citicoline may alleviate free fatty acid-induced toxicity which accompanies ischemic insult. Data from many pre-clinical and clinical trials support the hypothesis that citicoline may be a safe and effective treatment for stroke.

Language of Publication

English

Unique Identifier

96000742

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MeSH Heading (Major)

Cerebral Ischemia|*DT; Cytidine Diphosphate Choline|*TU

MeSH Heading

Animal; Cell Membrane|DE; Clinical Trials; Fatty Acids, Nonesterified|ME; Human; Membrane Lipids|ME; Neurons|DE/ME/UL; United States

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0161-6412

Country of Publication

ENGLAND

Record 15 from database: MEDLINE
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Title

New insight into the biochemical pathology of liver in choline deficiency.

Author

Ghoshal AK

Address

Department of Pathology, University of Toronto, Ontario, Canada.

Source

Crit Rev Biochem Mol Biol, 1995, 30:4, 263-73

Abstract

A diet deficient in choline can cause liver cancer in rats. The previous work since 1932 emphasized the fat-removing ability of choline from the liver. There are other dietary factors, including methionine, which, like choline, can remove fat from the liver. These factors were termed as lipotropes. Since then, choline deficiency and lipotrope deficiency are used synonoumously. Recent work since 1980 has clearly demonstrated that choline deficiency (CD) and lipotrope deficiency (LD) are not the same. Generation of free radicals, DNA alterations, liver cell death, and liver cancer that occur due to CD are not generated by LD. Generation of free radicals due to CD diet and some of the agents that counteract free radical action also prevent CD effects except for lipid accumulation in the liver. Despite the recent observations on the role of phospholipase A2 (PLA2) as the protector of the membranes, it has been found that by preventing the rise of PLA2 in the liver, cell death can be prevented. These new findings give choline a distinct role in liver cell death and cancer rather than the role of lipotrope. A new hypothesis linking dietary choline deficiency and liver cancer has been discussed.

Language of Publication

English

Unique Identifier

96058539

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MeSH Heading (Major)

Choline Deficiency|*ME/PA; Liver|DE/*ME/PA

MeSH Heading

Animal; Calcium|PD; Cell Death; Comparative Study; Diet|AE; Free Radicals|ME; Human; Lipid Peroxidation|DE; Lipids|ME; Liver Neoplasms|ET; Models, Biological; Phospholipases A|ME; Rats; Strontium|PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1040-9238

Country of Publication

UNITED STATES

Record 16 from database: MEDLINE
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Title

Liver biochemical pathology of choline deficiency and of methyl group deficiency: a new orientation and assessment.

Author

Ghoshal AK; Farber E

Address

Department of Pathology, University of Toronto, Ontario, Canada.

Source

Histol Histopathol, 1995 Apr, 10:2, 457-62

Abstract

New information on the pathologic effects of a choline deficient diet in the rat, in relation to the biochemical events, has led to a new understanding and orientation of the pathogenesis of both acute and chronic consequences in the liver. The biochemical pathology of choline deficiency is quite different than that of methyl group (lipotrope) deficiency. These studies in our laboratory and elsewhere are generating new insights and hypotheses concerning the genesis of hepatocyte necrosis and hepatocellular carcinoma in the rat fed a choline deficient diet.

Language of Publication

English

Unique Identifier

95322751

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MeSH Heading (Major)

Choline Deficiency|ME/*PA; Lipid Peroxidation|*PH; Liver|ME/*PA

MeSH Heading

Animal; Diet; Human; Methylation; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0213-3911

Country of Publication

SPAIN

Record 17 from database: MEDLINE
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Title

Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline.

Author

Weiss GB

Address

M. Hurley & Associates, Inc., Murray Hill, New Jersey 07974-1584.

Source

Life Sci, 1995, 56:9, 637-60

Abstract

CDP-choline, supplied exogenously as citicoline, has beneficial physiological actions on cellular function that have been extensively studied and characterized in numerous model systems. As the product of the rate-limiting step in the synthesis of phosphatidylcholine from choline, CDP-choline and its hydrolysis products (cytidine and choline) play important roles in generation of phospholipids involved in membrane formation and repair. They also contribute to such critical metabolic functions as formation of nucleic acids, proteins, and acetylcholine. Orally-administered citicoline is hydrolyzed in the intestine, absorbed rapidly as choline and cytidine, resynthesized in liver and other tissues, and subsequently mobilized in CDP-choline synthetic pathways. Citicoline is efficiently utilized in brain cells for membrane lipid synthesis where it not only increases phospholipid synthesis but also inhibits phospholipid degradation. Exogenously administered citicoline prevents, reduces, or reverses effects of ischemia and/or hypoxia in most animal and cellular models studied, and acts in head trauma models to decrease and limit nerve cell membrane damage, restore intracellular regulatory enzyme sensitivity and function, and limit edema. Thus, considerable accumulated evidence supports use of citicoline to enhance membrane maintenance, membrane repair, and neuronal function in conditions such as ischemic and traumatic injuries. Beneficial effects of exogenous citicoline also have been postulated and/or reported in experimental models for dyskinesia, Parkinson's disease, cardiovascular disease, aging, Alzheimer's disease, learning and memory, and cholinergic stimulation.

Language of Publication

English

Unique Identifier

95174506

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MeSH Heading (Major)

Cytidine Diphosphate Choline|*ME/*PD/PK/TU

MeSH Heading

Animal; Anoxia|DT/ME; Cell Membrane|DE/ME; Cells, Cultured; Head Injuries|DT; Human; Ischemia|DT/ME; Neurons|DE/PH; Phospholipids|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0024-3205

Country of Publication

ENGLAND

Record 18 from database: MEDLINE
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Title

Choline acetyltransferase: celebrating its fiftieth year.

Author

Wu D; Hersh LB

Address

Department of Biochemistry, University of Kentucky, Chandler Medical Center, College of Medicine, Lexington 40536-0084.

Source

J Neurochem, 1994 May, 62:5, 1653-63

Abstract

It is well known that the regulation of choline acetyltransferase (ChAT) activity under physiological and pathological conditions is important for the development and neuronal activities of cholinergic systems involved in many fundamental brain functions. This review focuses on recent progress in understanding the regulation of ChAT at the levels of both the protein and the mRNA. A deficiency in ChAT activity has been reported for neurodegenerative conditions such as Alzheimer's disease, amyotrophic lateral sclerosis, and schizophrenia. Although a major feature of ChAT regulation is likely to involve the spatial and temporal control of transcription, regulation of expression can also be at the level of RNA processing, transport/translocation, turnover, or translation. In addition, there is increasing evidence that ChAT might be regulated at the posttranslational level by compartmentation and/or covalent modification, i.e., phosphorylation, as well as noncovalent modification (protein-protein interaction, etc.). Synaptic activity and the state of neuronal transmission may also involve the regulation of ChAT at different levels via both positive and negative feedback loops, as was demonstrated in the characterization of two ChAT mutant Drosophila strains. Clearly, identification of cholinergic-specific elements and the characterization of the trans-acting factors that bind to them represent an important area of future research. Equally important is research on the mechanisms governing ChAT as an enzymatic entity. The future should be an exciting time during which we look forward to the elucidation of the cholinergic signal and its regulation as well as the determination of the three-dimensional structure of the enzyme.

Language of Publication

English

Unique Identifier

94209870

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MeSH Heading (Major)

Brain|*EN; Choline O-Acetyltransferase|BI/DF/*ME

MeSH Heading

Alzheimer Disease|EN; Amyotrophic Lateral Sclerosis|EN; Animal; Cloning, Molecular; Human; Protein Processing, Post-Translational; RNA, Messenger|ME; Schizophrenia|EN; Support, U.S. Gov't, P.H.S.; Transcription, Genetic; Translation, Genetic

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0022-3042

Country of Publication

UNITED STATES

Record 19 from database: MEDLINE
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Title

Lecithin and choline in human health and disease.

Author

Canty DJ; Zeisel SH

Address

Department of Nutrition, Food, and Hotel Management at New York University, NY.

Source

Nutr Rev, 1994 Oct, 52:10, 327-39

Abstract

Choline is involved in methyl group metabolism and lipid transport and is a component of a number of important biological compounds including the membrane phospholipids lecithin, sphingomyelin, and plasmalogen; the neurotransmitter acetylcholine; and platelet activating factor. Although a required nutrient for several animal species, choline is not currently designated as essential for humans. However, recent clinical studies show it to be essential for normal liver function. Additionally, a large body of evidence from the fields of molecular and cell biology shows that certain phospholipids play a critical role in generating second messengers for cell membrane signal transduction. This process involves a cascade of reactions that translate an external cell stimulus such as a hormone or growth factor into a change in cell transport, metabolism, growth, function, or gene expression. Disruptions in phospholipid metabolism can interfere with this process and may underlie certain disease states such as cancer and Alzheimer's disease. These recent findings may be appropriate in the consideration of choline as an essential nutrient for humans.

Language of Publication

English

Unique Identifier

95116033

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MeSH Heading (Major)

Choline|ME/*PD; Phosphatidylcholines|CS/ME/*PD

MeSH Heading

Animal; Choline Deficiency|ME; Human; Neoplasms|ME; Nutritional Requirements; Phospholipids|ME; Signal Transduction; Sphingosine|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0029-6643

Country of Publication

UNITED STATES

Record 20 from database: MEDLINE
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Title

A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline.

Author

Miller BL

Address

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

Source

NMR Biomed, 1991 Apr, 4:2, 47-52

Abstract

The structure and function of the chemicals contributing to the three main peaks seen with 1H NMR spectroscopy, N-acetyl-L-aspartate (NAA), creatine/phosphocreatine (Cr), and choline-containing compounds (Cho) is reviewed and the changes seen with these compounds in various disease states are briefly outlined. NAA is present within neurons although its biological function is largely unknown. NAA is elevated in several degenerative neurological conditions including amyotrophic lateral sclerosis and canavan disease, and in high concentrations it may behave like a neurotoxin. The creatine peak seen with 1H NMR spectroscopy consists of creatine and phosphocreatine which serve as a reserve for high-energy phosphates in the cytosol of muscle and neurons. They also buffer cellular ATP/ADP. The Cho peak seen with 1H NMR consists of a complex mixture of Cho-containing compounds. Cho is a precursor for the neurotransmitter acetylcholine and for the membrane constituent phosphatidylcholine. Future studies of changes seen in the Cho peak with stroke, degenerative dementia, drug intake, and infectious and neoplastic brain masses will be of great interest.

Language of Publication

English

Unique Identifier

91315964

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MeSH Heading (Major)

Aspartic Acid|*AA/CH; Brain Chemistry|*PH; Choline|*CH; Creatine|*CH

MeSH Heading

Human; Nuclear Magnetic Resonance|MT; Phosphocreatine|CH; Protons; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0952-3480

Country of Publication

ENGLAND

Record 21 from database: MEDLINE
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Title

Choline and human nutrition.

Author

Zeisel SH; Blusztajn JK

Address

Department of Nutrition, School of Public Health, University of North Carolina at Chapel Hill 27599-7400.

Source

Annu Rev Nutr, 1994, 14:, 269-96

Abstract

Choline is crucial for sustaining life. It modulates the basic signaling processes within cells, is a structural element in membranes, and is vital during critical periods in brain development. Choline metabolism is closely interrelated with the metabolism of methionine and folate. We believe that the normal human diet provides sufficient choline to sustain healthy organ function. However, vulnerable populations may become choline deficient, including the growing infant, the pregnant or lactating woman, the cirrhotic, and the patient fed intravenously. Further studies of choline requirements in these groups are required.

Language of Publication

English

Unique Identifier

95033449

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MeSH Heading (Major)

Choline|*/AD/ME/PH; Nutrition|*

MeSH Heading

Animal; Brain|GD/PH; Choline Deficiency; Human; Neoplasms; Nutritional Requirements; Phospholipids|PH; Signal Transduction; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0199-9885

Country of Publication

UNITED STATES

Record 22 from database: MEDLINE
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Title

Choline deficiency, lipotrope deficiency and the development of liver disease including liver cancer: a new perspective.

Author

Ghoshal AK; Farber E

Address

Department of Pathology, University of Toronto, Ontario, Canada.

Source

Lab Invest, 1993 Mar, 68:3, 255-60

Abstract

Thus, the pathologic consequences of feeding a CD diet are fatty liver, liver cell death, liver cell proliferation, and liver cell cancer. The fatty liver with CD is similar to that with other types of fatty liver in that the most attractive current hypothesis is based on some interference with the production and output of VLDL by the liver. The induction of cell death appears to be consistent with quite a different hypothesis, genesis and/or increase in liver free radicals leading to both acute necrosis and initiation of carcinogenesis. Especially noteworthy is the low incidence of liver cirrhosis, even after 2 years of exposure to the CD diet. The feeding of the CD diet reproducibly induces severe and persistent fatty liver coupled with extensive cell death, a combination that is frequently considered to be appropriate for the induction of "micronodular" (fatty) cirrhosis in humans. The findings with the LD diet, the high incidence of cirrhosis, with severe persistent fatty liver without significant cell death, together with the low incidence of cirrhosis with the CD diet, stand out as unpredictable and strange, according to current concepts of the pathogenesis of human cirrhosis. The CD model offers an unusual opportunity to explore in increasing detail the possible roles of free radicals in two important problems in pathology and medicine-acute cell injury and neoplasia. The challenges include mechanistic studies on how the free radicals are generated and how they relate to the biological consequences. The relatively slow sequential changes in the induction of cell injury and neoplasia makes the CD model one of the best for mechanistic studies relating to free radicals.

Language of Publication

English

Unique Identifier

93196136

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MeSH Heading (Major)

Carcinoma, Hepatocellular|*ET/ME/PP; Choline Deficiency|*CO/ME/PP; Lipotropic Agents|*ME; Liver Diseases|*ET/ME/PP; Liver Neoplasms|*ET/ME/PP; Metabolic Diseases|*CO/ME/PP

MeSH Heading

Human; Syndrome

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0023-6837

Country of Publication

UNITED STATES

Record 23 from database: MEDLINE
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Title

Choline phospholipids: signal transduction and carcinogenesis.

Author

Zeisel SH

Address

Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill 27599-7400.

Source

FASEB J, 1993 Apr, 7:6, 551-7

Abstract

Phospholipids act as vital elements in transmembrane signaling. Agonist-induced hydrolysis of phosphatidylinositides has been established as a major mechanism for transmitting messages into the interior of cells via protein phosphorylation cascades, ultimately regulating gene transcription. There is a growing body of evidence that choline phospholipids (phosphatidylcholine, sphingomyelin, and their metabolites) also are important mediators and modulators of transmembrane signaling. These functions may explain how choline phospholipids influence normal physiological processes as well as a diverse group of pathological processes.

Language of Publication

English

Unique Identifier

93231448

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MeSH Heading (Major)

Choline|*ME; Neoplasms|*ET/ME; Phospholipids|*ME; Signal Transduction|*

MeSH Heading

Animal; Human; Protein Kinase C|ME; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0892-6638

Country of Publication

UNITED STATES

Record 24 from database: MEDLINE
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Title

Choline acetyltransferase.

Author

Mautner HG

Address

 

Source

CRC Crit Rev Biochem, 1977 Nov, 4:4, 341-70

Abstract

Acetylcholine is essential to neural function. It synthesis is catalyzed by choline acetyltransferase, the enzyme responsible for the acetylation of choline by acetyl coenzye A, a reaction favored slightly thermodymodynamically and not at all kinetically. An analytically pure enzyme still has not been obtained; however, method of purification have been greatly improved recently. Numerous inhibitors of the enzyme have been synthesized and their structure-action relationships examained. Evidence has been accumulated showing the essential involvement of an imidazole group in the active site of choline acetyltransferase. The literature regarding the controversial role to thiol groups in choline acetyltransferase is reviewed. Recently, derivatives of coenzyme A have bee