The interconversion of serine and glycine: role of pteroylglutamic acid and other cofactors.

Considerable evidence has now been accumulated for the interconversion of glycine and serine in the aniimal body and in micro-organisms. Following the discovery by Shemin (1946) ofthe conversion of isotopically labelled serine into glycine in rats and guinea pigs, the reverse process, that is, the biosynthesis of serine from labelled glycine was also found to occur in the intact animal (Sakami, 1948, 1949). Incorporation of labelled glycine into serine hasbeen observed inrat-liver slices andhomogenates (Siekevitz, Winnick & Greenberg, 1949), and serine synthesis from glycine and [14C]formate or [14C]_ formaldehyde has been studied in soluble liver extracts (Deodhar & Sakami, 1953; Berg, 1953). Serine degradation to glycine and formaldehyde has been demonstrated in liver slices, extracts and homogenates (Vilenkina, 1952). Synthesis of serine from glycine and formate by washed cells of Streptococcus faecali8 R has been shown to require pteroylglutamic acid (PGA) in catalytic amounts (Lascelles & Woods, 1950), and there is also some evidence for the participation of PGA or a derivative in serine-glycine interconversion in mammalian tissues. Thus in folic aciddeficient rats less isotope from administered H14COOH is fixed into serine of body proteins than in normal animals, but the rate of incorporation of 14C into C-3 of serine becomes normal when the animals are fed PGA (Plaut, Betheil & Lardy, 1950). Elwyn & Sprinson (1950) have shown that [15N]serine is utilized less efficiently for hippuric acid synthesis in folic acid-deficient animals, and it was calculated that in folic acid deficiency the conversion of serine into glycine was reduced to one-sixth the normal rate. The addition of PGA or related compounds to tissue preparations has been shown to cause an increase in serine synthesis from formate (Kelley, 1951) and in serine breakdown to glycine and formaldehyde (Vilenkina, 1952). Recently, Rauen & Jaenicke (1953) have briefly reported evidence for serine synthesis from N10-formylPGA (II) and glycine in tissue homogenates and extracts. In the present investigation soluble enzyme preparations catalysing serine synthesis and break* Australian National University Scholar. Present address: John Curtin School ofMedical Research, Australian National University, Canberra, A.C.T., Australia. down (Blakley, 1954) have been used to study the role in these processes of PGA, its derivatives and some other cofactors. Another aspect of serine synthesis which has received attention in this work is the chemical identity of the immediate precursor of C-3 of serine. Labelled formate is incorporated into this position of the serine molecule by intact animals (Sakami, 1948), liver slices (Siekevitz & Greenberg, 1949) and liver extracts (Deodhar & Sakami, 1953), but Kruh0ffer (1951) has reported that in rat liver slices labelled glycine is incorporated into serine much more efficiently than labelled formate, and that in liver homogenates formate is not incorporated into serine even when incorporation of glycine into serine occurs. Furthermore, Siegel & Lafaye (1950) found that in rat-liver homogenates isotopic formaldehyde is much more rapidly incorporated into serine and into the methyl group of methionine than is formate or methanol. Evidence has been obtained in the present investigation for the view, consistent with these observations, that formaldehyde is an important precursor of serine C-3.