Biological activity of methylglyoxal and related aldehydes.

The effect of methylglyoxal and other aldehydes on several biochemical variables has been studied. Aldehydes inhibit amino acid incorporation into proteins, both in reconstituted systems and in isolated hepatocytes. They also decrease the secretion of protein and lipoprotein from hepatocytes into the incubation medium. This inhibition is seen even with prelabelled proteins, which indicates damage to the secretory mechanism itself. This conclusion is strenghened by the fact that aldehydes also decrease the binding of colchicine to liver tubulin. Aldehydes decrease the respiratory rate of mitochondria, as well as mitochondrial swelling induced by phosphate, by Ca2+ or by K+ plus valinomycin. They also partially inhibit cytochrome P-450. When injected into normal rats, aldehydes produce a decrease in the mitotic index of bone marrow cells and of the epithelial lining of the small intestine. A decrease in mitotic index and in cellularity is seen after injecting aldehydes into the peritoneal cavity of rats bearing transplanted ascites AH-130 Yoshida hepatoma. Aldehydes also impair the function of liver cell ligandin and potentiate the increase in cell permeability induced by 5-hydroxytryptamine (serotonin). The meaning of these results is discussed with special reference to the pathogenesis of cellular lesions in carbon tetrachloride poisoning.