Glycine serine interconversion

The enzyme catalyzing the glycine-serine interconversion has been demonstrated to occur in mammalian 35, 87, 89, SO, 34-37) and avian livers 38,38, 39), in bacteria 31, 40), and in higher plants 41). 

Figure 30-5. Interconversion of serine and glycine catalyzed by serine hydroxymethyltransferase. (H4 folate, tetrahydrofolate.)...

Nonketotic hyperglycinemia results from the congenital absence of the glycine cleavage system, which mediates the interconversion of glycine and serine 673... 

The pyridoxal-5 -phosphate dependent serine hydroxymethyltransferase (SHMT EC 2.1.2.1) in vivo catalyzes the interconversion of L-serine 158 and glycine 149 by transfer of the /1-carbon of L-serine to tetrahydrofolate (THF) by which the activated formaldehyde is physiologically made available as a C,-pool. The reaction is fully reversible and provides a means for the stereoselective synthesis of 158 in vitro from donor 149 and formaldehyde. Economical yields (88-94%) of L-serine have thus been obtained on a multimolar scale using raw cell extracts of recombinant Klebsiella aerogenes or E. coll in a controlled bioreactor at final product concentrations > 450 gl 1 [461,462], Several SHMTs have been purified and characterized from various organisms including animal tissues [463,464], eucaryotic [465] and procaryotic... 

Serine hydroxymethyltransferase is a PLP-dependent aldolase. It catalyzes interconversion between glycine and various P-hydroxy-a-amino acids, such as serine and threonine, via formation of a quinoid intermediate derived from PLP with the amino acid substrate (Scheme 2.9). This aldolase-type reaction is of interest as an asymmetric synthesis of a-amino acids via C-C bond formation. 

Once inside the cell, folates participate in a number of interconnected metabolic pathways involving (1) thymidine and purine biosynthesis necessary for DNA synthesis, (2) methionine synthesis via homocysteine remethylation, (3) methylation reactions involving S-adenosylmethionine (AdoMet), (4) serine and glycine interconversion, and (5) metabolism of histidine and formate (see Figure 8). Via these pathways. 

A transferase that also has aldolase activity and has been used to prepare a number of chiral compounds is the enzyme serine hydroxymethyltransferase (SHMT) (EC 2.1.2.1). This enzyme, also known as threonine aldolase, catalyzes the physiological reaction of the interconversion of serine and glycine with pyridoxal phosphate (PLP) and tetrahydrofolate (FH4) as the shuttling cofactor of the C-1 unit. It also catalyzes a number of other reactions, some of which are independent of PLP and FH4 [72]. The SHMT-catalyzed aldolase reaction generates two stereocenters, which it does stereospecifically at the (/.-carbon, whereas it is less strict at the [l-carbon (Scheme 13). Nevertheless, this enzyme from porcine liver, Escherichia coU and Candida humicola (threonine aldolase) has been used to prepare a number of P-hydroxy-a-amino acids [73-76],... 

Glycine participates in a number of synthetic pathways and is oxidized to provide energy (Figure 17-10). The interconversion of glycine and serine by serine hydroxymethyltransferase is shown below ... 

From these results we see that the 2-Hsj atom of glycine is replaced during the SHMT reaction and since L-serine has the (S) absolute configuration, the overall steric course at C is retention (see Fig. 14). A similar retention at C was shown in the interconversion of glycine into allothreonine (threonine). 

Depending upon the relative rates of the reactions participating in the interconversion of various species in the ternary complex, one may expect to see spectropho-tometrically the presence of the quinonoid intermediate of type 6 (Fig. 42) in a number of pyridoxal-P-dependent enzymic reactions such an intermediate would be expected to possess a bathochromically shifted long wavelength absorption maximum. This has indeed been clearly viewed for the ternary complex of serine hydroxymethyltransferase with glycine as shown in Fig. 46, the absorption at 495 nm being attributed to the quinonoid intermediate [94]. 

Major pathways for the synthesis and interconversion of glycine and serine in plants are outlined in the scheme in Fig. 1. The most studied pathway, the glycolate pathway, is that associated with photosynthesis and responsible for photorespiration (see Tolbert, this series, Vol. 2, Chapter 12). Flux through this pathway is rapid especially in the leaves of C3 plants. Alternatives to the glycolate pathway exist in green and nongreen tissues but because of slower turnover rates evidence for them from experiments using isotopic tracers is less clear and the enzymes concerned are more difficult to study because of their lower concentration in the tissues. 

Fig. 1. Main routes involved in the synthesis and interconversion of glycine and serine in plants. The various steps are numbered, and the necessary enzymes are as follows 1, glycolate oxidase, E.C. 1.1.3.1 2, aminotransferases, serine, E.C. 2.6.1.45, and glutamate, E.C. 2.6.1.4, glyoxylate aminotransferases 3, enzyme complex in mitochondria (see Fig. 2) 4, serine-glyoxylate aminotransferase, E.C. 2.6.1.45 5, glycerate dehydrogenase, E.C. 1.1.1.29 6, glycerate kinase E.C. 2.7.1.31 7, D-3-phosphoglycerate phosphatase, E.C. 3.1.3.38 8, d-3-phosphoglycerate dehydrogenase, E.C. 1.1.1.95 9, phosphoserine aminotransferase, E.C. 2.6.1.52 10, phosphoserine phosphatase, E.C. 3.1.3.3 11, serine hydroxymethyltransferase E.C. 2.1.2.1 12, nonenzymatic decarboxylation 13, formyl tetrahydrofolate synthetase, E.C. 6.3.4.3 14, isocitrate iyase, E.C. 4.1.3.1.

Keys, A. J. Synthesis and interconversion of glycine and serine. In The Biochemistry of Plants, Vol. 5, Amino Acids and Derivatives (B. J. Miflin, ed.), pp. 359-374. Academic Press, New York 1980... 

Serine-Glycine Interconversion. Feeding experiments in animals showed the formation of glycine from serine and threonine. An interconveision of serine and glycine was indicated by microbial nutritional experiments and confirmed by isotope experiments with both microbial and animal preparations. The carboxyl and a-carbon of serine are converted to gly-... 

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