Serine hydroxymethylase

Rat liver aminomalonate decarboxylase has recently been identified with cytoplasmic serine hydroxymethylase and allothreonine aldolase 17>. Most references in this narrative have been omitted, since they can all be found in Popjack s review t). 

Palekar, A. G., Tate, S. S., Meister, A. Rat liver aminomalonate decarboxylase. Identity with cytoplasmic serine hydroxymethylase and allothreonine aldolase. J. Biol. Chem. 248, 1158-1167 (1973). 

This kind of reaction is exemplified by serine hydroxymethylase, an enzyme that requires both PLP and tetrahydrofolate as coenzymes. The aldimine produced upon the reaction of serine with (30), i.e. (31 R = CH2OH), loses formaldehyde via abstraction of the /3-hydroxyl proton (i.e. an aldol cleavage) to give (33). The formaldehyde that is produced is immediately trapped by the tetrahydrofolate cofactor to give iV(5,10)-methylenetetrahydrofolate... 

B-73MI11001,77B1093). (33) is then protonated at the substrate a-carbon to yield an aldimine, the hydrolysis of which produces glycine as product (equation 15) and regenerates PLP. The reaction catalyzed by serine hydroxymethylase is important because it supplies the necessary one-carbon units required in biosynthesis (see also Section 1.10.5.2). 

The names serine hydroxymethylase 89) and serine aldolase 34) have been proposed for the enzyme. The basis for the name serine aldolase is that the synthesis of serine is an aldol condensation and that a number of similar enz3une reactions are known, namely, for the decomposition of threonine to acetaldehyde and glycine and of phenylserine to benzaldehyde and glycine. It has been partially pmrified from sheep 34), beef 36), rabbit 35), and chicken 36) livers by standard procedures for protein purification. Extracts of acetone powders of liver have been used mainly as the starting materials. 

Huennekens and Osborn 44) calculated the equilibrium constant for the intrinsic serine hydroxymethylase reaction [Eq. (2)] to be if = 4.6. 

FH4 can also react chemically nth formaldehyde as shown in experiments by Blakley (43) and Kisliuk (44) and the product so formed is able to react enzymically with glycine to form serine. In biological systems, however, the donor of the single-carbon unit to FH4 at the HCHO level of oxidation may be serine via the serine hydroxymethylase reaction (4S). Recently an enzyme termed hydroxymethyl-FH4 dehydrogenase that catalyzes the interconversion of 10-hydrox3rmethyl-FH4 and 10-formyl-FH4 or their respective ring anhydrides by triphosphopyridine nucleotide has been purified from beef liver by Hatefi et al. (46). This important enzyme links the two derivatives of FH4 that function metabolically at either the formyl or formaldehyde level of oxidation. 

Serine hydroxymethylase (serine hydroxymethyltransferase) (EC 2.1.2.1) Serine hydroxymethylase [Eq. (7)] has been purified 1550-fold fi-om soybean... 

Serine hydroxymethylase was purified to homogeneity from mung beans (Vigna radiata) (Rao and Appaji Rao, 1982). It required one of the substrates to be present for stability as well as a sulfhydryl reducing agent. Activity was optimal at pH 8.5 and the enzyme had two temperature optima, 35 and 55°C. The substrate dependence was biphasic vnth respect to serine with values of... 

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