ALDOSE REDUCTASE IS A MAJOR REDUCTASE FOR ISOCAPROALDEHYDE, A PRODUCTOF SIDE-CHAIN CLEAVAGE OF CHOLESTEROL, IN HUMAN AND ANIMAL ADRENAL-GLANDS

Isocaproaldehyde (4-methylpentanal) is a product of the side-chain cle avage of cholesterol, the first step of steroid biosynthesis. Here, we report the characterization of enzymes responsible for the oxidoreduc tion of isocaproaldehyde in human, monkey, dog, and rabbit adrenal gla nds, NADPH-linked isocaproaldehyde reductase activity in the adrenal e xtracts of the four species was much higher than the NADH-linked reduc tase and NAD(P)(+)-linked dehydrogenase activities and was potently in hibited by aldose reductase inhibitors. The major species of isocaproa ldehyde reductase purified from the four mammalian adrenal glands were biochemically identical with aldose reductase, and exhibited K-m valu es of 1 mu M. The contents of aldose reductase in adrenal glands of th e four mammals were relatively high, and its localization in canine ad renal cortex was immunohistochemically demonstrated. In addition, the purified aldose reductases and recombinant human aldose reductase redu ced other alkanals and alkenals at low K-m values of 2-61 mu M, and th eir catalytic efficiencies were higher than that of human aldehyde red uctase, Thus, aldose reductase acts not only as a major reductase for isocaproaldehyde formed from steroidogenesis but also as a scavenger o f aldehydes derived from lipid peroxidation in mammalian adrenal gland s. (C) 1996 Academic Press, Inc.