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Handbook of Neurochemistry and Molecular Neurobiology pp 443–501Cite as

Choline and Its Products Acetylcholine and Phosphatidylcholine

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Abstract:

Choline, a quaternary amine obtained largely from the diet but also synthesized in the brain and, especially, liver, is an essential precursor of the neurotransmitter acetylcholine (ACh) and of the major membrane constituent phosphatidylcholine (PC). Plasma choline concentrations can vary over a fivefold range depending on the choline contents of the foods being digested. Since choline readily crosses the blood–brain barrier (BBB) through an unsaturated facilitated-diffusion system, these plasma changes can produce parallel changes in brain choline levels. In addition, since the enzymes that convert choline to ACh [choline acetyltransferase (ChAT)] and PC's precursor phosphocholine [choline kinase (CK)] are also poorly saturated with their choline substrate, increases in plasma choline can enhance the formation of ACh and phosphocholine, and the release of ACh. The subsequent conversion of phosphocholine to PC is increased if PC's other circulating precursors (uridine and omega-3 fatty acids) are provided. This leads to an increase in the levels of synaptic membrane within the brain. Choline is principally metabolized in the liver to betaine, which provides a source of methyl groups for the regeneration of methionine and S-adenosylmethionine.

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Abbreviations

5-methyl-THF:

5-methyl-tetrahydrofolate

5,10-MTHF:

5,10-methylene-tetrahydrofolate

AA:

arachidonic acid

ACh:

acetylcholine

AChE:

acetylcholinesterase

ACTH:

adrenocorticotropic hormone

AI:

adequate intake

AMPA:

DL-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid

APP:

amyloid precursor protein

BBB:

blood-brain barrier

BuChE:

butyrylcholinesterase

CaM-kinase:

Ca+2/calmoduline kinase

CDP:

cytidine-5′-diphosphate

CDP-choline:

cytidine-5′-diphosphocholine

ChAT:

choline acetyltransferase

CHT:

high-affinity choline transporter

CK:

choline kinase

CMP:

cytidine-5′-monophosphate

CNS:

central nervous system

CNT:

concentrative nucleoside transporter

CP:

choroid plexus

CPT:

CDP-choline:1,2-diacylglycerol cholinephosphotransferase

CT:

CTP:phosphocholine cytidylyl transferase

CTL:

choline-transporter-like protein

CTP:

cytidine-5′-triphosphate

DAG:

diacylglycerol

DHA:

docosahexaenoic acid

ECF:

extracellular fluid

ENT:

equilibrative nucleoside transporter

EPA:

eicosapentaenoic acid

EPT:

CDP-choline:1,2-diacylglycerol ethanolaminephosphotransferase

FAD:

flavine adenine dinucleotide

FNB:

Food and Nutrition Board

GH:

growth hormone

GPC:

glycerophosphocholine

GPC-CPD:

Glycerophosphocholine cholinephosphodiesterase

GPC-PD:

glycerophosphocholine phosphodiesterase

GRAS:

generally regarded as safe

HC3:

hemicholinium-3

IP3:

inositol triphosphate

LH:

luteotropic hormone

LHRH:

luteinizing hormone-releasing hormone

LPCAT:

lyso-phosphatidylcohline acyltransferase

LTP:

long-term potentiation

mAChR:

muscarinic acetylcholine receptor

MAPK:

mitogen-activated protein kinase

nAChR:

nicotinic acetylcholine receptor

NAD:

nicotinamide adenine dinucleotide

NDPK:

nucleoside diphosphate kinase

NGF:

nerve growth factor

NMDA:

N-methyl-D-aspartate

OCT:

organic cation transporter

PAF:

platelet-activating factor

PC:

phosphatidylcholine

PCho:

phosphocholine

PE:

phosphatidylethanolamine

PEMT1:

phosphatidylethanolamine-N-methyltransferase

PEMT2:

phosphatidyl-N-methylethanolamine-N-methyltransferase

PK:

protein kinase

PKA:

protein kinase A

PLA1:

phospholipase A1

PLA2:

phospholipase A2

PLC:

phospholipase C

PLD:

phospholipase D

PS:

phosphatidylserine

PUFA:

polyunsaturated fatty acid

RDA:

recommended daily allowance

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

SM:

sphingomyelin

THF:

tetrahydrofolate

TRH:

thyrotropin-releasing hormone

TSH:

thyroid-stimulating hormone

UL:

upper limit

UCK:

uridine-cytidine kinase

UMP:

uridine-5′-monophosphate

UDP:

uridine-5′-diphosphate

UTP:

uridine-5′-triphosphate

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Acknowledgments

The authors thank Dr. Jan Krzysztof Blustajn and Ms. Carol Watkins for the critical review of this chapter. Studies described in this chapter were supported in part by grants from the National Institutes of Mental Health (MH-28783); the NIH-NCRR (5-MO1RR01066–29); the Center for Brain Sciences and Metabolism Charitable Trust; and the Turkish Academy of Sciences (Ismail H. Ulus).

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  1. R. J. Wurtman
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  2. M. Cansev
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  3. I. H. Ulus
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Medical Chemistry, Biochemistry and Biotechnology, Via Saldini 50, 20133, Milan, Italy

    Guido Tettamanti

  3. Department of Internal Medicine Section of Biochemistry, University of Perugia, via del Giochetto, 06122, Perugia, Italy

    Gianfrancesco Goracci

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Wurtman, R.J., Cansev, M., Ulus, I.H. (2009). Choline and Its Products Acetylcholine and Phosphatidylcholine. In: Lajtha, A., Tettamanti, G., Goracci, G. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30378-9_18

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