2-Amino-4-hydroxy-6-formyldihydropteridineの代謝

概要

論文の詳細を見る
Dephosphorylation of dihydroneopterin triphosphate (I) formed from GTP by GTP cyclohydrolase has remained as an unknown step in dihydrofolate (II) biosynthesis. The present author and Brown have found in Escherichia coli at least two hydrolytic enzymes : one, named as dihydroneopterin triphosphate pyrophosphohydrolase, catalyzes the removal of PPi specifically from (I) to give dihydroneopterin monophosphate (III) as the product, and the other catalyzes the hydrolysis of (III) to dihydroneopterin (IV). 2-Amino-4-hydroxy-6-carboxydihydropteridine (V), but not 2-amino-4-hydroxy-6-carboxypteridine (VI), inhibits enzymatic synthesis of (II) from GMP by specific attacking an enzyme reaction catalyzed by 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine (VII) pyrophosphokinase. Also, (V) inhibits growth of E. coli, while (VI) does not affect the growth, demonstrating that (V) blocks the growth by antagonizing utilization of (VII) for (II) synthesis. The growth inhibition is reversed by 2-amino-4-hydroxy-6-formyldihydropteridine (VIII). But, when (V) is absent, (VIII) blocks the growth with an inhibitory power about equal to (V). The mechanism whereby this contradictory effect of (VIII) on the growth happens, and the biological significance of this phenomenon has been explored by following metabolism of (VIII) and 2-amino-4-hydroxy-6-formylpteridine (IX). Three possible directions of (IX) metabolism in vivo are estimated by testing the inhibitory powers on xanthine oxidase of various pteridines related to (IX) in their structures : the 1st conversion is to (VI), the 2nd to 2-amino-4-hydroxy-6-hydroxymethylpteridine (X), and the 3rd to (VIII). The most potent inhibitory action of (IX) is extremely reduced by these conversion, which are found in E. coli. Dihydropteroate (XI), a precursor of (II), is enzymatically formed from (VIII) and (IX) via (VII), since these transformations are inhibited strongly by (V). The enzymatic conversion of (VIII) to (VII) is catalyzed by a specific reductase dependent on NADPH, and the conversion of (IX) to (VIII) requires FAD and NADH as the cofactors. The transformation of (IX) to (VII) via (X) is not plausible, since the enzyme system is not found to reduce the pyrazine ring of (X). (VI) is produced from (IX) by a NAD^+-specific aldhyde dehydrogenase, but not by xanthine oxidase. The synthetic pathway of (II) from (IX) via (VIII) is characterized as a "salvage route" for formation of (II), which could function dominantly under reduction of folate coenzymes levels by blockage of the main biosynthetic pathway from GTP, resulting in reversal by (VIII) of E. coli growth inhibition produced by (V). Mathis and Brown (1970) have found the strong inhibition by (VIII) of dihydroneopterin aldolase in the biosynthetic pathway of (II). If (VIII) is produced as the catabolic product from the folate coenzymes, this inhibition may have a nature of "feed-back inhibition", whereby the physiological levels of folate coenzymes could be maintained in the cells, and excess addition of (VIII) results in inhibition of E. coli growth.
日本ビタミン学会の論文
1974-02-25

2-Amino-4-hydroxy-6-formyldihydropteridineの代謝

スポンサーリンク

概要

著者

関連論文

スポンサーリンク