Inhibition of Flavin Adenine Dinucleotide Pyrophosphorylase by Isoriboflavin

Abstract

RIBOFLAVIN antagonism by some analogues of the vitamin may be attributable to inhibition of one or more of the following : the flavokinase-catalysed conversion of riboflavin to flavin mononucleotide (PMN), the pyrophosphorylase-catalysed conversion of FMN to flavin adenine dinucleotide (FAD), and the coenzymatic activities of FMN and FAD. Isoriboflavin (5,6-dimethyl-9-(1′D-ribityl)isoalloxazine) has been shown to be an effective antagonist to riboflavin in the growing organism¹. This analogue has no reactivity in the flavokinase system where it acts neither to inhibit the normal conversion of riboflavin to FMN nor as an artificial substrate to produce an analogue of FMN^2,3. However, it was noted that isoriboflavin inhibits the coenzymatic function of FMN with triphosphopyridine nucleotide–cytochrome c reductase from yeast⁴. More recently, chemically synthesized isoriboflavin-5′-phosphate was shown to be a substrate in lieu of FMN with FAD pyrophosphorylase⁵ ; a finding which suggested that isoriboflavin might act as an inhibitor to the normal substrate function of FMN with the pyrophosphorylase. This communication presents direct evidence for the inhibition of FAD pyrophosphorylase by isoriboflavin.