Cysteine metabolic fate

SAM) by methionine adenosyltransferase. SAM serves as a methyl donor for a variety of methyl acceptors, including DNA, protein, neurotransmit-ters, and phospholipids. 5-Adenosylhomocysteine (SAH) is produced following methyl donation by SAM, and homocysteine is formed through the liberation of adenosine from SAH by the enzyme SAH hydrolase. Unlike methionine and cysteine, homocysteine is not incorporated into polypeptide chains during protein synthesis. Instead, homocysteine has one of two metabolic fates transsulfuration or remethylation to methionine. 

As discussed in Section 10.3.4.2, the metabolic fate of homocysteine arising from methionine is determined not only by the activity of cystathionine synthetase and cystathionase, hut also the rate at which it is remethylated to methionine (which is dependent on vitamin B12 and folate status) and the requirement for cysteine. 

The identification of hyperhomocysteinemia as an independent risk factor in atherosclerosis and coronary heart disease (Section 10.3.4.2) has led to suggestions that intakes of vitamin Be higher than are currently considered adequate to meet requirements may be desirable. Homocysteine is an intermediate in methionine metabolism and may undergo one of two metabolic fates, as shown in Figure 9.5 remethylation to methionine (a reaction that is dependent on vitamin B12 and folic acid) or onward metabolism leading to the synthesis of cysteine (trans-sulfuration). Therefore, intakes of folate, vitamin B12, and/or vitamin Be may affect homocysteine metabolism. 

As shown in Figure 10.9, the methyl donor is S-adenosyl methionine, which is demethylated to S-adenosyl homocysteine. After removal of the adenosyl group, homocysteine may undergo one of two metabolic fates remethylation to methionine or condensation with serine to form cystathionine, foUowed by cleavage to yield cysteine - the transulfuration pathway (Section 9.5.5). Cystathionine synthetase has a relatively low Tni compared with normal intra-ceUular concentrations of homocysteine. It functions at a relatively constant rate, and under normal conditions, most homocysteine wUl be remethylated to methionine. 

A metabolism study was conducted in male Wistar rats to determine the fate of the salt of 3-mercapto-2-oxopropionic acid, the intermediate product in the transamination pathway of L-cysteine metabolism. Results showed that the salt of 3-mercapto-2-oxopropionic acid is metabolized by reduction and frans-sulfuration to yield 3-mercaptolactate cysteine mixed disulfide (S-(2-hydroxy-2-carboxyethylthio) cysteine) and inorganic sulfate, respectively. The reduction is catalysed by lactate dehydrogenase, as indicated by the use of anti-lactate dehydrogenase antiserum. 

Homocysteine metabolism involves three key enzymes methionine synthase, betaine homocysteine methyl transferase (BHMT) and cystathione p-synthase. Both vitamin B12 and folate are required in the methylation of homocysteine to methionine via metheonine synthase after donation of a methyl group from SAM during the methylation process. Homocysteine is also methylated by betaine in a reaction catalysed by BHMT and does not involve vitamin B12 and folate. The other metabolic fate for homocysteine is the transsulfuration pathway which degrades homocysteine to cysteine and taurine, and is catalysed by cystathione p-synthase with vitamin Bg as coenzyme. 

Figure 9-3. Fates of the carbon skeletons upon metabolism of the amino acids. Points of entry at various steps of the tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis are shown for the carbons skeletons of the amino acids. Note the multiple fates of the glucogenic amino acids glycine (Gly), serine (Ser), and threonine (Thr) as well as the combined glucogenic and ketogenic amino acids phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). Ala, alanine Cys, cysteine lie, isoleucine Leu, leucine Lys, lysine Asn, asparagine Asp, aspartate Arg, arginine His, histidine Glu, glutamate Gin, glutamine Pro, proline Val, valine Met, methionine.

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