Choline methyl group source

The question therefore arose about the fate of the methyl group from methionine. When minimal amounts of methionine were used to supplement the diet of rats given homocysteine as their main source of sulfur, the rats did not usually thrive, and at death had fatty accumulations in their livers. Best and his co-workers had earlier reported the efficacy of choline as a lipotropic agent, facilitating the mobilization of fat from the liver. Du Vigneaud therefore tried supplementing homcys-... 

Homocysteine (Hey) metabolism is closely linked to that of the essential amino acid methionine and thus plays a central role in several vital biological processes. Methionine itself is needed for protein synthesis and donates methyl groups for the synthesis of a broad range of vital methylated compounds. It is also a main source of sulphur and acts as the precursor for several other sulphur-containing amino acids such as cystathionine, cysteine and taurine. In addition, it donates the carbon skeleton for polyamine synthesis [1,2]. Hey is also important in the metabolism of folate and in the breakdown of choline. Hey levels are determined by its synthesis from methionine, which involves several enzymes, its remethylation to methionine and its breakdown by trans-sulphuration. 

Choiine. Choline is a component of many biomem-hranes and plasma phospholipids. Dietary sources include eggs. fish, liver, milk, and vegetables. These sources provide choline primarily as the phospholipid lecithin. Lecithin is hydrolyzed to glycerophosphorylcholinc by the intestinal mucosa before absorption. The liver liberates choline. Choline can be biosynthesized by humans con.sequcntly. it cannot be con.sidcred a (rue vitamin. Biosynthesis involves methylation of cthanolamine. The methyl groups arc provided by methionine or by a reaction involving vitamin B12 and folic acid. Therefore, deficiencies can occur only if all methyl donors are excluded from the diet. 

The importance of SAM in metabolism is reflected in the several mechanisms that provide for the synthesis of sufficient amounts of its precursor, methionine, when the latter molecule is temporarily absent from the diet. For example, choline is used as source of methyl groups to convert homocysteine into methionine. Homocysteine can also be methylated in a reaction utilizing N5-methyl THF. This latter reaction is a bridge between the THF and SAM pathways (Figure 14.17). 

Methionine is an essential amino acid with a unique role in the initiation of protein synthesis, hi addition, by conversion to 5 -adenosyhnethionine, it serves as the major methyl group donor involved in the formation of creatinine and choline, in the methylation of bases in RNA, and as the source of the aminopropyl group in the formation of polyamines. Finally, in relationship to classical homocystinuria, it is converted by way of homocysteine and cystathionine in a series of reactions termed as the transsulfuration pathway (Fig. 20.3). 

Choline is considered to be an important member of the vitamin B complex, since most animals, when given diets low in this compound, develop deficiency characterized by fatty livers and hemorrhagic lesions of the kidney. Choline is believed to function in at least three ways (1) as an integral part of acetylcholine, (2) as a source of labile methyl groups, and (3) in stimulating the formation of phospholipids. 

Little is known of choline requirement in either animals or man since the need is dependent, in part, on other sources of methyl groups in the diet, namely methionine and betaine. Elvehjem has suggested that, in the light of animal studies, the human requirement is probably less than 500 mg. daily. This amount may be furnished by the average diet which contains about 250 to 600 mg. of choline. 

Choline is a source of methyl groups for metabolic activity. It is not always grouped with the water-soluble B vitamins. It can be made in the body, but under some conditions it might become essential in the diet. In various species choline deficiency has been associated with fatty liver, cirrhosis, hemorrhagic kidney, and later development of a renal type of hypertension. The significance of these findings in man is not established, and there is, as yet, no clear therapeutic value of supplying choline in human diets, as distinct from other dietary improvement. Therefore any dietary requirement can not be estimated. 

EUNCTIONS. Choline has several important functions in the body. As a constituent of several phospholipids (primarily lecithin), it prevents fatty livers through the transport and metabolism of fats as a constituent of acetylcholine, it has a role in nerve transmission and by a phenomenon known as transmethylation, it serves as a source of labile methyl groups, which facilitate metabolism. 

Choline Transport and metabolism of fats source of methyl groups fCH, . 

The sources of the methyl groups of choline can be certain Ci moieties and the methyl group of methionine. Recent experimental work suggests that the Ci compounds are first transformed into the methyl group of methionine and it is the latter that finds its way by transmethylation to become the methyl groups of choline (69-61). 

Wilson et al. (60) obtained evidence that methionine is the immediate source of all methyl groups of choline and that Ci compounds are channeled through this amino acid. This evidence is that in rat liver slices unlabeled ethanolamine and formate did not affect the incorporation of methionine-... 

Ethanolamine cephalins are formed in the same way, i.e. ethanolamine is activated with CDP and transferred onto a diglyceride. Cephalins may be methylated to produce lecithins with adenosylmethionine as methyl group donor. This methyla-tion apparently is the main biosynthetic pathway of lecithin and is an important source of choline from ethanolamine (Greenberg and Bremer). 

Choline occupies a key position between energy and protein metabolism. Two types of choline functions are known as choline per se, for which the choline moiety is required, and in the function of a methyl donor. Choline per se plays a major role in lipid metabolism, particularly in lipid transport, as lipotropic agent, but it is also an important source of labile methyl groups for the biosynthesis of other methylated compounds. Based on this second function, choline and methionine pathways partially overlap in providing methyl groups in a variety of reactions. Based on these assumptions we investigated the effects of rumen protected choline administration on milk production in dairy cows. To achieve this pourpose a meta-analysis was carried out to summarize available scientific evidence for the effect of oral rumen protected choline (RPC) supplementation in dairy cows. 

Choline, an essential nutrient for humans, is consumed in many foods. It is part of several major phospholipids (including phosphatidylcholine - also called lecithin) that are critical for normal membrane structure and function. Also, as the major precursor of betaine it is used by the kidney to maintain water balance and by the liver as a source of methyl groups for the removal of homocysteine in methionine formation. Finally, choline is used to produce the important neurotransmitter acetylcholine (catalyzed by choline acetyltransferase in cholinergic neurons and in such non-nervous tissues as the placenta). Each of these functions for choline is absolutely vital for the maintenance of normal function. 

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