Alteration of hepatic mitochondrial aldehyde dehydrogenase activity by sodium arsenate: The relationship to mitochondrial-microsomal oxidative interactions

Abstract

Prolonged oral exposure of rats to sodium arsenate produces marked alteration of hepatic mitochondrial structure and a pronounced increase in the NAD/NADH ratio with a concomitant 2.8-fold increase in the endogenous specific activity of NAD-dependent mitochondrial aldehyde dehydrogenase. There was no change in K m or V max of the enzyme for either formaldehyde or NAD. Mitochondria from arsenate-treated rats combined in vitro with microsomes from the same animals were found to metabolize formaldehyde generated from microsomal dealkylation reactions at approximately 1.4 times the rate observed with control mitochondria. These results indicate that a change in the mitochondrial NAD/NADH ratio by exposure to arsenate may affect interorganelle biological processes in vivo. These results may be important in understanding the metabolic consequences of the shifts in mitochondrial redox state associated with arsenate alterations of mitochondrial metabolic activities.