Characteristics of alcohol dehydrogenase in fat-storing (Ito) cells of rat liver.

Fat storing (Ito) cells, located in the perisinusoidal spaces of the liver and the main storage site of vitamin A, have been associated with fibrogenesis. The mechanisms of alcoholic liver disease, although mostly unknown, do involve ethanol metabolism. This study examined the ability of fat-storing cells to metabolize ethanol. Alcohol dehydrogenase activity was detected in fat-storing cells of the rat liver. The enzyme was demonstrated also by enzyme-linked immunosorbent assay and immunohistochemical staining. The enzyme in fat-storing cells is similar to the hepatocyte enzyme in its Michaelis-Menten constants for substrates and coenzymes and in the competitive inhibition by ethanol of retinol oxidation. It differs from the hepatocyte enzyme by its greater susceptibility to inhibition by 4-methylpyrazole and by having a single isoelectric point of 9.5 as compared with multiple isoelectric points in the hepatocyte ranging from 6.9 to 8.8. The ability of the fat-storing cell to oxidize ethanol and the inhibitory effect of ethanol on retinol oxidation may be important in the pathogenesis of alcoholic liver disease.