Serine, catabolism hydroxymethyltransferase

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

Disposal of Surplus One-Carbon Fragments With the exception of serine hydroxymethyltransferase (Secdon 10.3.1.1), aU of the reactions shown in Figure 10.4 as sources of one-carbon subsdtuted folates are essentially catabolic reactions. When there is a greater entry of single carbon units into the folate pool than is required for biosynthetic reactions, the surplus can be oxidized to carbon dioxide byway of 10-formyl-tetrahydrofolate, thus ensuring the avaUabUity of tetrahydrofolate for catabolic reactions. 

Rat liver apparently contains a serine hydroxymethyltransferase in the cytosol and another inside the inner membrane of the mitochondria. The two enzymes have different properties (Palekaref al., 1973). The concerted operation of serine hydroxymethyltransferase in the cytosol with the conversion of glycine to serine in mitochondria of liver probably forms the main mechanisms for catabolism of glycine (Kikuchi, 1973 Cybulski and Fisher, 1976). In ureotelic animals the C, produced is oxidized to CO2 whereas in birds and other uricotelic animals Ci is needed with glycine for synthesis of uric acid. Extramitochondrial serine hydroxymethyltransferase in plants may be needed for synthesis of glycine, serine, and active Ci but may serve a catabolic function also. 

The third catabolic route would be by the conversion of the 1 and 2 carbon atoms of serine to glycine with the concomitant producticm of methylene THF from C-3 (reaction 5). The enzyme catalyzing this reaction is serine hydroxymethyltransferase (E.C. 2.1.2.1). It has been found in a number of higher plants and partially purified from tobacco root (Prather and Sisler, 1966) and cauliflower bud (Mazelis and Liu, 1967). The glycine formed can then be degraded by the pathways described above (Section 1I,E). The methylene-THF can be oxidized to the Ai-formyl THF and then to CO2 and THF. This latter reaction has been reported in pea mitochondria by Clandinin and Cossins (1975). 

The main source of C, units is the hydroxymethyl group of serine, which is transferred to THF by serine hydroxymethyltransferase (EC 2.1.2.1), forming fV -hydroxymethyl-THF (activated form dehyde). Production of C, units during histidine catabolism and in the anaerobic degradation of purines is of particular importance. C, units are incorporated during purine biosynthesis, and they provide the S-methyl group of thymine. C units are interconverted while attached to THF (Hg.2). For other metabolic sources and uses of C units, see legend to Fig.2. 

Serine hydroxymethyltransferase is a pyridoxal phosphate-dependent enzyme that catalyses the cleavage of serine to glycine and methylene-tetrahydrofolate. Whereas folate is required for the catabolism of variety of compounds, serine is the most important source of substituted folates for biosynthetic reactions, and the activity of serine hydroxymethyltransferase is regulated by the state of folate substitution and the availability of folate. The reaction is freely reversible, and under appropriate conditions in liver it functions to form serine from glycine, as a substrate for gluconeogenesis (section 5.7). 

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