The Biosynthesis of Folic Acid. Iv. Enzymatic Synthesis of Dihydrofolic Acid from Guanine and Ribose Compounds.

In 1954, Albert (2) suggested that purmes may be biological precursors of pteridine compounds. This suggestion was made as a result of his demonstration that purines can be transformed chemically into pteridines under mild conditions in the presence of glyoxal. The first experimental evidence that the biogenesis of purines and pteridines are biologically related was provided by Weygand and Waldschmidt (3), who injected glycine-14C and formate-14C into butterfly larvae and found that these compounds were incorporated into a pteridine pigment, leucopterin, isolated from the wings of the butterfly. The labeling pattern suggested that purines and pteridines are formed by similar biosynthetic pathways. Recent investigations from a number of laboratories have indicated that purines can be used directly for the formation of pteridines. Thus, Ziegler-Gtinder, Simon, and Wacker (4) reported that guanine-2-r4C is efficiently incorporated into a pteridine compound by Xenopus; Brenner-Holeach and Leuthardt (5,6) demonstrated that a purine is probably a precursor of pteridine pigments in Drosophila melarwgastcr; and Weygand et al. (7) have proposed that guanine or guanosine 5’-phosphate is a direct precursor of xanthopterin and leucopterin in the butterf ly Pieris brass&e L. Also, Vieira and Shaw (8) found that administration of adenine-2-14C t,o whole cells of a species of Corynebactcrium resulted in the formation of significant quantities of radioactive pteroyltriglutamic acid (Teropterin) ; administration of adenine-8-14C resulted in no radioactive Teropterin. These workers concluded that adenine was metabolized by the bacteria so that carbon atom 8 of adenine was removed and the remaining portion of the purine compound was used directly for the synthesis of the pteridine portion of the Teropterin molecule. Carbohydrates can also be efficiently incorporated into the pteridine ring. Weygand et al. (7) have reported that both radioactive glucose and ribose can be incorporated into the leucopterin of butterflies. The labeling pattern from ribose indicated that carbon atoms 6 and 7 of this pteridine are derived from carbon atoms 2 and 1 of ribose, respectively (see Fig. 1 for the formula of leucopterin and the numbering system for the pteridine ring). Brenner-Holeach and Leuthardb (4,5) also concluded that ribose is incorporated into the pteridine pigments of Drosophila meknw-