Serine catabolism

Serine. Following conversion to glycine, catalyzed by serine hydroxymethyltransferase (Figure 30—5), serine catabolism merges with that of glycine (Figure 30-6). 

Figure 20.15 Interrelationships between the serine and glycine metabolic pathways. FH4-"C" indicates 5,10-methylenetetrahydrofolate. (Adapted from Yoshida T, Kikuchi G. Comparative study on major pathways of glycine and serine catabolism in vertebrate livers. ) Biochem 72 1503-1516, 1972.)...

The major pathway of serine catabolism probably is by way of its enzymatic dehydration and subsequent spontaneous deamination to yield pyruvic acid (see Fig. 2). An evidence for this is the observation of Lien and Greenberg that alanine is the major amino acid formed from serine-3-C by liver mitochondrial preparations. The alanine could be fomed from the pyruvic acid by transamination. 

Serine, like alanine, is converted into pyruvate by a PLP-dependent pathway, but the two reaction sequences are not the same. Whereas alanine catabolism involves a PLP-dependent transamination, serine catabolism involves a PLP-dependent dehydration to form an intermediate enamine that is then hydrolyzed. 

Show the mechanisms of the final step in serine catabolism, hydrolysis of the imine to give pyruvate. 

In addition to its conversion to glycine, shown in Fig. 1, other possible pathways of serine catabolism are represented in Fig. 2. 

A number of investigators have attempted to determine the major pathways of serine catabolism from distribution of the C Mabel of isotopic serine in glycogen and other amino acids in the intact rat (47, 4S) and in a variety of products in rat liver slices (49). The results indicated that the metabolic pathways of L-serine and D-serine are quite distinct. In other respects there is no general agreement. Koeppe and co-workers (47, 4S) determined that conversion to pyruvate is an important pathway of L-serine degradation, while an important product of unknown nature is formed as an intermediate from D-serine. Elwyn et al. (49) concluded that conversion to glycine is probably the major pathway for L-serine metabolism. 

There are several catabolic pathways for serine (Appendix 8.3). 

More recently, Pearce and Heydeman suggested non-oxidative removal of ethylene glycol units as acetaldehyde by a membrane-bound, oxygen-sensitive enzyme of a novel type, i.e., diethylene glycol lyase (18). Schoberl suggested that PEG was catabolized by Ci step, liberating formate which was metabolized by a serine pathway (19). 

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

The carbon skeletons of six amino acids are converted in whole or in part to pyruvate. The pyruvate can then be converted to either acetyl-CoA (a ketone body precursor) or oxaloacetate (a precursor for gluconeogenesis). Thus amino acids catabolized to pyruvate are both ke-togenic and glucogenic. The six are alanine, tryptophan, cysteine, serine, glycine, and threonine (Fig. 18-19). Alanine yields pyruvate directly on transamination with... 

In the biosynthesis of serine from glycine, (25) serves as the methylene donor. The reverse of this reaction is important in the catabolism of serine and provides a major source of the one-carbon units needed in biosynthesis (80MI11003). In addition to tetrahydrofolate, pyridoxal phosphate is required as a coenzyme in this transformation. The topic will be taken up again in the next section. 

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