Choline synthesis

Leslie, G.M. and Buckley, G.T. (1976). Phospholipid composition of goldfish (Carassius auratus) liver and brain and temperature-dependence of phosphatidyl choline synthesis. Comparative Biochemistry and Physiology 53B, 335-337. 

Dopamine is also the precursor for noradrenaline and adrenaline biosynthesis. Phosphatidylethanolamine is the precursor for choline synthesis, Section 14.2.1. ... 

Phosphatidylcholine (lecithin) is not required in the diet because it can be synthesized in the body. The components of phosphatidylcholine (including choline) all can be produced, as shown in Figure 33.28. A pathway for de novo choline synthesis from glucose exists, but the rate of synthesis is inadequate to provide for the necessary amounts of choline. Thus, choline has been classified as an essential nutrient, with an Al (adequate intake) of 425 mg/day in females and 550 mg/day in males. 

It is believed that the vitamin B12 requirement for choline synthesis contributes to the neurologic symptoms of vitamin B12 deficiency. The methyl groups for choline synthesis are donated by SAM, which is converted to S-adenosylho-mocysteine in the reaction. Recall that formation of SAM through recycling of homocysteine requires both tetrahydrofolate and vitamin B12 (unless extraordinary amounts of methionine are available to bypass the B12-dependent methionine synthase step). 

Choline is a common component of the diet bnt also can be synthesized in the human as part of the pathway for the synthesis of phospholipids (see Chapter 33). The only route for choline synthesis is via the sequential addition of three methyl groups from SAM to the ethanolamine portion of phosphatidylethanolamine to form phosphatidylcholine. Phosphatidylcholine is subsequently hydrolyzed to release choline or phosphocholine. Conversion of phosphatidylethanolamine to phosphatidylcholine occurs in many tissues, including liver and brain. This conversion is B6- and B 12-dependent. 

You would expect to see reduced rates of synthesis of triacylglycerols, which use diacyl-glycerols as acceptors of activated acyl groups. In addition, phosphatidyl choline synthesis is dependent on the availability of diacylglycerols as acceptors of choline phosphate from CDP-choline. 

Lipotropic substances compounds directly or indirectly involved in fat metabolism, which can prevent or correct fatty degeneration of the liver. They serve as substrates of phosphatide biosynthesis, or contribute (e.g. by methylation) to the synthesis of these substrates. Thus choline and any substance capable of contributing methyl groups for choline synthesis (e.g. methionine) are L.s. Liver is the major site of synthesis of plasma phosphoglycerides when the availability of choline is restricted, the rate of phosphatidylcholine synthesis decreases, and the rate of removal of fatty acids from the liver falls below normal. If the rate of supply of fatty acids (free and esterified) to the liver remains normal, the resulting accumulation of fat gives rise to the condition of fatty liver, or fatty degeneration of the liver. 

When fed in place of choline it was observed that dimethylamino-ethanol prevented fatty liver but led to poor growth on a homocystine diet, whereas the monomethyl compound was quite toxic. The interpretation to be placed on this result is that the di- and monomethyl-aminoethanols can be converted to choline by being methylated, but cannot serve as methyl donors themselves. The conversion of ethanol-amine to choline by successive methylation steps has received support from a study of choline synthesis in cholineless mutants of Wewrospora. Monomethylaminoethanol was isolated from the culture media of one cholineless mutant, and it was found to support the growth of a second cholineless mutant. This is evidence that the monomethyl derivative is an intermediate in the synthesis of choline by Neurospora. Dimethyl-aminoethanol promotes the growth of both strains. 

Thus, the metabolic needs for choline can be supplied in either of two ways by dietary choline as such, or by choline synthesis in the body which makes use of labile methyl groups. But the synthesis in the body cannot take place fast enough to meet the choline needs for rapid growth hence, the symptoms of deficiency may result. 

A substance that prevents accumulation of fat in the liver. Choline is probably the most important of the lipotropic factors. So, any substance capable of contributing methyl groups for choline synthesis is lipotropic. 

The data of the previous section have indicated that brain tissue is able to convert endogenous Ptd-ethanolamine to Ptd-choline by the stepwise methylation pathway. The fact that the addition of exogenous PDE brings about higher rate of Ptd-choline synthesis and the different results obtained at two different pH values with and without PDE addition already indicated that the methyl transferases acting upon membrane-bound Ptd-ethanolamine might be functioning at different pH optima. 

The physiological significance of this metabolic pathway in brain is unknown. Its occurrence in nervous tissue might be of some importance due to the possibility for the nerve cell to enrich its Ptd-choline fraction of polyunsaturated fatty acids, particularly 20 4 and 22 6, Moreover, the Ptd-choline synthesis by the methylation pathway in red blood cells has been indicated to represent a mechanism for an enzymeHnediated flip-flop of phospholipids from the cytoplasmic to the outer surface of erythrocyte m nbranes, producing fluidity variations in the same membrane vhich might affect ion movement and enzyme activities. It is possible that such implication can be drawn also for nervous membranes,... 

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