Role of 2-Amino-4-Hydroxypteridine-6-Carboxaldehyde in Folic Acid Biosynthesis. ∗

Abstract

Recent studies on folic acid biosynthesis have focused attention on the role of P-6-CH₂OH‡ as an immediate pteridine precursor of the vitamin. This report describes studies which demonstrate the inhibition of growth of E. coli ATCC 9723 (Roepke Strain) by P-6-CH₂OH. This inhibition is reversed by dihydrofolic acid and even more effectively by dihydro P-6-CHO.‡ The implications of these results for folic acid biosynthesis are discussed.

The current state of information regarding the biochemical sequence leading to folic acid may be summarized as follows: Guanosine-5′-triphosphate is ring-opened in the imidazole portion of the molecule and carbon eight is lost. Subsequent cyclization of the ribosyl moiety forms the pyrazine ring to give 2-amino - 4 - hydroxy - 6 - trihydroxypropyl pteri-dine, probably in a reduced form. This compound is then further metabolized to give 7,8-dihydropteroic acid and ultimately dihydrofolk acid.

The fact that carbons 6,7, and 9 of folic acid originate as carbons 2′, 1′, and 3′, respectively, of the ribosyl moiety of guanylic acid is well established (1). It thus appears clear that a 2-amino-4-hydroxypteridine with a single carbon substituent in position six is an intermediate between the trihydroxypropyl pteridine and folic acid. A number of investigators have indicated this precursor to be a reduced form of P-6-CH₂OH (2,3,4). These earlier findings have now been extended and the proposed intermediate is thought to be dihydro P-6-CH₂OH pyrophosphate (5).

Therefore, although a role for dihydro P-6-CH₂OH pyrophosphate appears to be established, no details of the metabolic sequence from the trihydroxypropyl pteridine to this immediate folate precursor are known. The role of P-6-CH₂OH in this pathway, if any, remains obscure. Like folk acid, P-6-CH₂OH has been indentified as a metabolite of guanine(6).