Hepatic xanthinedehydrogenase. II. Receptors of electrons coupled enzymatically

Abstract

Hepatic Xanthinedehydrogenase. II. Acceptors of Electrons Coupled Enzymatically

The formation of uric acid from xanthine by the action of a xanthinedehydro­ genase implies an electronic transfer from the substrate to an immediate acceptor, which, in the cases of bird hepatic or renal enzymes, can be the cellular NAD+.

In this paper, the enzymatic dehydro- genation of xanthine by human and por­ cine liver dehydrogenases has been stu- died in the presence of different electrón acceptors. Although NAD+ appears to be a less efficient acceptor for mammalian xanthinedehydrogenases than for the chicken hepatic enzyme, the dinucleotide can effectively bridge the electrón current towards piruvic acid or a-oxoglutaric acid when either lacticdehydrogenase or glutamicdehydrogenase are also present. Thecoupling of xanthinedehydrogenase with the lactic- (or glutamic-) dehydrogenase systems brings about a significant increa­se in the uric acid production.

These phenomena have been observed with both pig liver and chicken liver xanthinedehy­drogenases.

It has been previously shown that sali- cylic acid, phenylbutazone and colchicine are powerful inhibitors of hepatic xan­thinedehydrogenases. Now we have found that although salicylic slightly inhibits lacticdehydrogenase, phenylbutazone is a vigorous inhibitor of both lactic- and glutamic-dehydrogenases, whereas colchicine induces a strong inhibition of lacticdehy­ drogenase only. It is suggested that the inhibiting properties of the said drugs may be intimately related with the therapeutical effects attained when they are administered for the treatment of gout and similar diseases, imputed to an exalted uricogenesis.