A study of the mechanism of serine biosynthesis.

Elwyn et al. (1, 2) have demonstrated that the C1 unit formed from serine is of the oxidation level of formaldehyde rather than formate. They compared the dilution of the Cl4 and deuterium of 2 ,3-deuterio-3-C14,N15L-serine that occurred during the conversion of the serine B-carbon to methyl groups in rats. The results indicated that this carbon did not pass through an intermediate, such as formate, which required the loss of 1 of the hydrogen atoms. In consideration of the results of Elwyn et al. and the general implication of the cit,rovorum factor, 5-formyl-5,6,7 ,&tetrahydrofolic acid, in the metabolism of C1 compounds, Welch and Nichol (3) proposed that the C1 unit formed from serine was a reduced form of citrovorum factor, 5-hydroxymethyl-5,6,7,8-tetrahydrofolic acid, a hypothetical condensation product of formaldehyde and tetrahydrofolic acid. The formulation of the biosynthesis of serine as a process involving a condensation between the a-carbon of glycine, activated by the Schiff base formation with pyridoxal phosphate (4)) and 5-hydroxymethyl-5,6,7,8tetrahydrofolic acid is reminiscent of the Mannich reaction (5). Serine would be produced by hydrolytic cleavage of the resulting product. The conversion of serine to glycine could occur by the reverse process. The participation of THFA’ as a cofactor in the biosynthesis and cleavage of serine has been studied by adding it to pigeon liver extracts incubated anaerobically with glycine-1-V and L-serine. The assumption underlying this procedure was that the formation and breakdown of serine were catalyzed by a single enzyme. In this case, the ,&carbon atom of the L-serine would provide the C1 unit for the conversion of glycine-l-Cl4