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By M L Anson; Kenneth Bailey; John T Edsall

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It therefore seems that endogenously synthesized glycine is not extensively converted into the “active” one-carbon compound. This conclusion is supported by the observation that the conversion of the methylene group of glycine into urinary formate is considerably less than that of other onecarbon precursors such as sarcosine, methionine, or acetone (Weinhouse and Friedmann, 1952). 52 H. R . V. ARNSTEIN Formate, too, docs not appear to be a very important piecursor of the hydroxymethyl group of serine, hut is more extensively converted into the methyl group of methionine (Arnstein and Neuberger, 1953a).

The known biosynthetic reactions of glycine and the ultimate reaction products are summarized below (Table V and Fig. 2). In many cases the precise structure of the other reactants which participate in these biosyntheses is not known, and therefore only the metabolic origin of these substances is given in Table V. 1. The Condensation of Glycine with One-Carbon Compounds Related to Formaldehyde and Formate a. The Formation of Serine. The metabolic conversion of glycine into serine was first observed by Winnick, Moring-Claesson, and Greenberg 49 METABOLISM OF OLYCINE TABLE V Biosynthetic Reactions of Glycine - Reactive position of glycine Metabolic source of other reactant Cof actors required Probable intermediates } Carboxyl car- Amino acids bon, Nitrogen Carboxyl car- Ammonia bon a-Carbon Formaldehyde Reaction product Proteins Uric acid Tetrahydropteroylglutamic acid a-Carbon Succinic acid Coenzyme A a-Carbon Nitrogen Nitrogen Nitrogen Nitrogen Carbon dioxide Arginine Formate Benzoic acid Coenzyme A r-GlutamylATP cysteine Formyl or methylol derivative of tetrahydropteroylglutamic acid 6-Aminolevulinic acid Serine Porphyrins Uric acid GIycocy amine Creatine Uric acid Hippuric acid Glut athione (1948) in rat liver homogenates and by Sakami (1948), who showed that in the intact rat glycine condenses with C14-formateto give serine labeled almost entirely in the p-carbon atom: HC"0zH + CHzNHz*COzH-+ C'4HzOH*CHNHz*C0zH It is now known that in this reaction, which is probably the reverse of the cleavage of serine (Shemin, 1946), glycine condenses with an "active" one-carbon compound related to formaldehyde rather than t o formate, and it is likely that the "active" intermediate is N6-hydroxymethyltetrahydropteroylglutamic acid or a similar derivative.

Hirs and Rittenberg (1950) have reported experiments indicating that in liver slices citrulline is aminated primarily by ammonia, although aspartic acid may also be utilized, as suggested by the work of Ratner and Pappas (1949a,b) with purified enzyme systems. Glycine may apparently also contribute nitrogen for urea formation without prior conversion into ammonia, at least in liver slices (Hirs and Rittenberg, 1950), although this reaction seems to be quantitatively unimportant and may be explained by the possible occurrence of limited transamination.

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