Ch3

Choline

Choline O-acetyl -transferase

Acetyi-CoA

CH3 Acetylcholine figure 8.110 Acetylcholine synthesis and breakdown each ol'thc three catabolic steps alter that generates the one-carbon donor methylene tetra hydro folate. Hits gives choline a central role in the homeostasis of hormone synthesis. DNA methylation. and other critical metabolic events. Neurotransmission. A small amount of the intracellular choline, probably from phosphatidylcholine. is used for the synthesis of acetylcholine in neurons of the brain and the parasympathetic nervous system. Choline O-acetyltransferase (choline acetyl-transferase, EC2.3.1.G) is responsible for the synthesis. Acetylcholine is cleaved again by acetylcholine esterase (YT blood group antigen. EC3.1.1,7), Complex lipids: Choline is an important constituent of structural lipids such as phosphatidylcholine (membranes, digestive micelles, lipoproteins, intracellular signaling), sphingomyelin (enhances neural conductivity), and platelet-activating factor (hormonelike action). The synthesis of phosphatidyl choline starts with choline phosphorylation by choline kinase ( EC'2.7,1,32). CTP phosphocholine cyt idyl transferase (EC2.7.7.15 ) then generates the activated form and magnesium-dependent diacylglvcerol choline-phosphotransferase (CDP-choline:diacyl glycerol choline phosphotransferase, EC2.7.8.2) adds the 1.2-diacy(glycerol moiety.

Countercurrent hypertonia; The choline metabolite betaine is an important osmolyte in epithelial cells from the renal inner medulla that helps to concentrate urine. Expression of the betaine transporter (SLC6A12) in renal medulla is induced by hypertonicity. A similarosmoprotective function may be important lor intestine (Kidd etui. 1997):

Ernyme activation: The activity of some enzymes is increased by phosphatidylcholine. A pertinent example is the allostcric activation of 3-hydroxybutyrate dehydrogenase (EC1.1.1.30), an enzyme of ketone body metabolism.

H?H? CHa Choline

Choline kinase

0 CHa

Phosphochotine

OTP phosphochotine cytidytiransferase

o o CH3

OH OH

OH OH

Di acyl glycerol cholinephospho-transf erase (Mg' J

H2C—acyl acyl CH Q CH3

Figure 14,111 Phosphatidylcholine synthesis from choline

Cancer; Choline deficiency increases cancer risk in various rodent models. An important mechanism may Lie inadequate DNA methylation due to a diminished pool of one-carbon groups. Many cancers are characterized by increased choline kinase activity, v^iich effectively traps choline in affected cells (Roivainen el ai. 2000), This phenomenon can be employed for radiological identification of some cancer cells by positron emission tomography (PfiT) after administration of 1 'C-labeled choline. Cell cycle regulation: Choline deficiency increases the rate of apoptotic cell death in manv tissues (Shin et at., 1997).

References

Arndt P. Volk C, Gorboulev V. Budiman T. Popp C. Ulzlieimer-Teuber I, Akhoundova A, Koppatz S. Bamberg E, Nagel G, Koepsell II. Interaction of cations, anions, and weak hase quinine with rat renal cation transporter rOCT2 compared with rOCTI, Am J PhysioI Renal Fluid Electrolyte Physiol 2001:2S 1 :F454 -68 Ayesh R, Mitchell St . Zhang A. Smith RL. The fish odour syndrome: biochemical, familial. and clinical aspects. Br Med J 1993:307:655-7 Ayuk PTY. Sibley CP. Donnai P. D'Souza S. Glazier JD. Development and polarization of cationic amino acid transporters and regulators in the human placenta lm J Physiol Cell Physiol 2000;278:C 1162-C1171 Dowhan W. Phosph at idyl serine decarboxylases:pyruvoyl-dependent enzymes from bacteria to mammals. Methods Enzymol 1997:280:81-8 Ebel H. Hollstein M. GuntherT. Role of the choline exchanger in Na( + ^independent

Mg(2 + ) efflux from rat erythrocytes. Biachim Biophys Acta 2002:1559:135-44 Grassl SM, Choline transport in human placental brush border membrane vesicles. Biochim

Biophys Acta 1994:1194:203 13 Habibulla M. Newburgh RW. Carnitine decarboxylase and phosphokinase in Phormia regino. J Insect Physiol 1969:15:2245 53 Kaplan CP. Porter RK, Brand MD, The choline transporter is the major site of control of choline oxidation in isolated rat liver mitochondria. FEBS Lett 1998:321:24-6 Kettunen II, l'eu ran en S.Tiihonen K. Saarinen M, Intestinal uptake of betaine in vitro and the distribution of methyl groups from betaine. choline, and methionine in the body of broiler chicks. Camp Biochem Physiol A 2001:128:269-78 Kidd MT, Ferket PR, Garlich .ID. Nutritional and osmoregulatory functions of betaine.

Poultry Sci 1997;53:125-39 Kobayashi Y. ( )kuda T. Fujioka Y. Matstimura G, Nishimura Y, Haga T. Distribution of the high-afTmity choline transporter in the human and macaque monkey spinal cord. Neurosci Lett 2002:317:25-8 Lock man PR. Roder KF. Allen Dl). Inhibition of the rat blood-brain barrier choline transporter by manganese chloride../ Nettrochem 2001;79:588-594 Porter RK, Scott JM, linind MD. Choline transport into rat liver mitochondria. Characterization and kinetics of a speciiic transporter. J Biol ( liem 1992:267; 14637-46

Punimer S. Dantzler WH, Lien YH. Moeckel GW. Volker K, Silbeniagl S. Reabsorption of betaine in Denies loops of rat kidney in vivo, tm J Physiol Renal Fluid Electrolyte Physiol 2000; 278 :F434-F434 Keubet BE. Karl C. Reimann SA, Mihalik SJ. Dodt ( i. Cloning and functional expression of a mammalian gene l'or a peroxisomal sarcosine oxidase. ./ Biol Client 1997; 272:6766-76

Roivainen A, l orsback S, GronroosT. Lehikoiunen P, Kiihkoncn M. Sutincne L, Minn II Blood metabolism of [methyl-1 lC]choline; implications for in vivo imaging with positron emission tomography. Eur J Sue! Med 2(^X1:27:25 32 Shin OH. Mar Mil. Albnyhi CD. Citarelia MT. da Costa KA, Zeisel Sll. Methyl-group donors cannot prevent apoptotic death of rat hepatocytes induced by choline-deficiency. J Cell Biochem 1997:64:1% 208

Sweet DU, Miller DS. Pritehard JB. Ventricular choline transport: a role for organic cation transporter 2 expressed in choroid plexus. J Biol Cheni 2001:276:41611 19 Takanaga IL Ohtsuki S.! I o soy a K. Terasaki f. GAT2 BOT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood brain barrier. J Cereb Blood Flow Met ab 2001 £1:1232-9 Trcaey 1:1'. Akerman BR, Chow LML. Youil R. Bibeau C, Lin J, Bruce AO, Knight M. Danks DM. Cashman JR. Forrest SM. Mutations of the (lavin-containing monooxy-genasc gene (FM03) cause trimethylaminuria, a defect in detoxication. Hum Mol Genet 1998;7:839-45

/eise I SH, Choline. In Shits ML. Olson JA. Shike M, eds. Modern Nutrition in Health and Disease, Lea <fc Febiger. Philadelphia. 1994. pp.449-58

Understanding And Treating Autism

Understanding And Treating Autism

Whenever a doctor informs the parents that their child is suffering with Autism, the first & foremost question that is thrown over him is - How did it happen? How did my child get this disease? Well, there is no definite answer to what are the exact causes of Autism.

Get My Free Ebook


Post a comment