(b) Choline plays an essential role in fat metabolism in the liver. It prevents abnormal accumulation of fat (fatty livers) by promoting its transport as lecithin or by increasing the utilization of fatty acids in the liver itself. Choline is thus referred to as a "lipotropic" factor due to its function of acting on fat metabolism by hastening removal or decreasing deposition of fat in liver.
(c) Choline is essential for the formation of acetylcholine, a substance that makes possible the transmission of nerve impulses. Acetylcholine is the agent released at the termination of the parasympathetic nerves. As acetylcholine, there is transmission of nerve impulses from presynaptic to postsynaptic fibers of sympathetic and parasympathetic nervous systems.
(d) Choline is a source of labile methyl groups. Choline furnishes labile methyl groups for formation of methionine from homocystine and of creatine from guanidoacetic acid. Methyl groups function in the synthesis of purine and pyrimidine, which are used in the production of DNA. Methionine is converted to S-adenosylmethionine in a reaction catalyzed by methionine adenosyl transferase. S-adenosylmethionine is the active methylating agent for many enzymatic methylations. A disturbance in folic acid or methionine metabolism results in changes in choline metabolism and vice versa (Zeisel, 1990). The involvement of folic acid, vitamin B12, and methionine in methyl group metabolism, and of methionine in de novo choline synthesis, may allow these substances to substitute in part for choline. A severe folic acid deficiency has been shown to cause secondary liver choline deficiency in rats (Kim et al., 1994).
The demand for choline as a methyl donor is probably the major factor that determines how rapidly a diet deficient in choline will induce pathology. The pathways of choline and 1-carbon metabolism intersect at the formation of methionine from homocysteine. Methionine is regenerated from homocysteine in a reaction catalyzed by betaine: homocysteine methyltransferase, in which betaine, a metabolite of choline, serves as the methyl donor (Finkelstein et al., 1982). Large increases in chick hepatic betaine-homocysteine methyltransferase can be produced under methionine-deficient conditions, especially in the presence of excess choline or betaine (Emmert et al., 1996). To be a source of methyl groups, choline must be converted to betaine, which has been shown to perform methylation functions as well as choline in some cases. However, betaine fails to prevent fatty livers and hemorrhagic kidneys.
Since choline contains biologically active methyl groups, methionine can partly be spared by choline and homocysteine. Research with lactating dairy cattle suggests that a high proportion of dietary methionine is used for choline synthesis (Erdman and Sharma, 1991).
