Methionine 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. 

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. 

Creatine is an amino acid derivative synthesized from arginine, glycine, and methionine in the kidneys, liver, and pancreas (see Figure 9.1). The metabolic fate of creatine is conversion to creatinine and excretion in the uiine." ... 

Metabolic Fate of the Methyl Carbon Atom of Methionine in I mna ... 

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.

K6. Kinsell, L. W., Harper, H. A., Bartow, H. C., Hutchin, M. E., and Hess, J. R., Studies in methionine and sulfur metabolism. I. The fate of intravenously administered methionine in normal individuals and in patients with liver damage. J. Clin. Invest. 27, 677-688 (1948). 

Figure 20.17 Metabolism of methionine. FH4 indicates tetrahydrofolate. A and B indicate defects in homocystinuria and cystathioninuria, respectively, and the asterisk indicates the fate of the methionine carbon skeleton.

It could be converted selenocysteine (SeCys) to selenomethionine (SeMet) and dimethylselenide (DMSe) - SeCys to SeMet via the action of three enzymes (Fig. 6.3). The first, cystathionine-y-synthase (CyS), couples SeCys to 0-phosphohomoserine to form Se-cystathionine. The second enzyme, cystathionine-(3-lyase, converts Se-cystathionine into Se-homocysteine. These first two enzymes are thought to be chloroplastic. However, the next step occurs in the cytosol. Se-homocysteine is converted to SeMet via the action of Met synthase. SeMet has multiple possible fates, one of which is to be methylated to methyl-SeMet via the enzyme methionine meth-yltransferase. Methyl-SeMet can be further metabolized to volatile DMSe, which is cleaved off of the intermediate, dimethylselenopropionate (DMSeP), by DMSeP lyase (Pilon-Smits and Quinn 2010). 

This article provides an overview of developments in sulfur metabolism and related processes in plants since the pubhcation of Volume 5. Some older literature which predates Volume S but which is now relevant to some of the new topics contained in this article is also included. Various excellent and more detailed reviews on specialized aspects of sulfur metabolism are available. They include reviews on utathione (Rennenbeig, 1982), the fate of excess sulfur (Rennenbeig, 1984), sulfate reduction and assimilation (Schiff, 1983 Schmidt, 1982a), r ulation of sulfur metabolism (Schmidt, 1986), the recycling of methionine associated with the synthesis of ethylene and polyamines (Miyazaki and Yang, 1987a Yang and Hoffman, 1984), and the effect of SO2 on chloro-plast metabolism (Alscher et ai, 1987). 

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