IDENTIFICATION OF HORMONALLY CONTROLLED ENDOGENOUS INHIBITOR OF LIVER NICOTINAMIDE DEAMIDASE

A study has been carried out of the hormonally controlled endogenous inhibitor of nicotinamide deamidase, the enzyme which catalyzes the first and presumably rate-limiting step in the biosynthesis of NAD from nicotinamide. The inhibitory material has been purified and found to consist of a mixture of free fatty acids, the predominant ones being oleic, linoleic and arachidonic. A synthetic mixture of authentic fatty acids of the same composition as the purified inhibitor imitated the inhibitory potency of the latter. A variety of individual free fatty acids of varying chain-length and degree of unsaturation were tested for their ability to inhibit the purified enzyme. The more potent fatty acids caused 50% inhibition at concentrations of about 2 μM. The present results indicate that the effects of the endocrine system on the levels of free acids contribute to the mechanism of hormonal regulation of NAD synthesis from nicotinamide. © 1969.