Metabolism of serine, glycine, and threonine

See also Table 5.1, Genetic Code, Metabolism of Serine, Glycine, and Threonine, Figure 2L24, Figure 21.25, Essential Amino Acids... 

See also Metabolism of Serine, Glycine, and Threonine, Essential Amino Acids... 

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.

The metabolism of P-hydroxy-a-amino adds involves pyridoxal phosphate-dependent enzymes, dassified as serine hydroxymethyltransferase (SHMT) (EC 2.1.2.1) or threonine aldolases (ThrA L-threonine selective = EC 4.1.2.5, L-aHo-threonine selective = EC 4.1.2.6). Both enzymes catalyze reversible aldol-type deavage reactions yielding glycine (120) and an aldehyde (Eigure 10.45) [192]. 

This reaction is readily reversible. Another means of metabolizing serine, which accounts for its glucogenic character, as well as that of glycine, is the conversion of serine to pyruvate, as indicated in Figure 20.12. This reaction is catalyzed by serine dehydratase. A similar enzyme, threonine dehydratase, converts threonine to a-ketobutyrate, and the latter is then converted to propionyl-CoA, as indicated in Figure 20.13. Another similar enzyme, cysteine desulfhydrase, con-... 

Choline kinase phosphorylates choline to give a phosphocholine and participates in glycine, serine and threonine metabolism and glycerophospholipid metabolism. Hemicholinium-7 is the prototypical tool compound used to inhibit CHK. Based on inhibitor studies, it has been proposed that CHK is important for the regulation of cell proliferation. Inhibition of choline kinase is also used to target plasmodium and develop novel antimalarials. A series of papers on pyridinium based inhibitors have been published, but no disclosures of more drug-like molecules have been made. 

Fig. 39.6. Metabolism of glycine. Glycine can be synthesized from serine (major route) or threonine. Glycine forms serine or CO and NH4+ by reactions that require tetrahydrofolate (FH4). Glycine also forms glyoxylate, which is converted to ox ate or to CO2 and H2O.

The metabolism of j5-hydroxy-a-amino acids involves pyridoxal phosphate-dependent enzymes, classified as serine hydroxymethyltransferase or threonine aldolases, that catalyze reversible aldol-type cleavage to aldehydes and glycine (134) [284]. 

Metabolism of P-hydroxy-a-amino acids involves pyridoxal phosphate-dependent enzymes that catalyze a reversible cleavage to aldehydes (Fig, 31) and glycine (89). The distinction between L-threonine aldolase (ThrA EC 4.1.2.5), L-a//o-threonine aldolase (EC 4.1.2.6), or serine hydroxymethyltransferase (SHMT EC 2.1,2.1) has often been rather vague since many catalysts display only poor capacity for erythro/threo (i.e., 91/90) discrimination [22]. Many enzymes display a broad substrate tolerance for the aldehyde acceptor, notably including variously substituted aliphatic as well as aromatic aldehydes (Fig. 31) however, a,P-unsaturated aldehydes are not accepted. 

D-hydroxyphenylglycine, L-hydroxyproKne, L-isoleucine, L-lysine, L-ornithine, L-phenylalanine, o-phenylglycine, L-polylysine, L-proline, L-serine, L-threonine, L-tryptophan, and L-tyrosine) was investigated and successfully manufactured on an industrial scale. Glycine is produced by chemical methods because the molecule has no chiral center, and methionine is also produced by chemical methods in its racemic form because the main use of the amino acid is as feedstuff. o-Methionine is metabolized in animals by the action of D-amino acid oxidase. These amino acids were useful as sources of medicines, food additives, feed-stuffs, and starting materials for chemical synthesis. 

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