Aldose reductase is a major reductase for isocaproaldehyde, a product of side-chain cleavage of cholesterol, in human and animal adrenal glands.
Isocaproaldehyde (4-methylpentanal) is a product of the side-chain cleavage of cholesterol, the first step of steroid biosynthesis. Here, we report the characterization of enzymes responsible for the oxidoreduction of isocaproaldehyde in human, monkey, dog, and rabbit adrenal glands. NADPH-linked isocaproaldehyde reductase activity in the adrenal extracts of the four species was much higher than the NADH-linked reductase and NAD(P)(+)-linked dehydrogenase activities and was potently inhibited by aldose reductase inhibitors. The major species of isocaproaldehyde reductase purified from the four mammalian adrenal glands were biochemically identical with aldose reductase, and exhibited Km values of 1 microM. The contents of aldose reductase in adrenal glands of the four mammals were relatively high, and its localization in canine adrenal cortex was immunohistochemically demonstrated. In addition, the purified aldose reductases and recombinant human aldose reductase reduced other alkanals and alkenals at low Km values of 2-61 microM, and their catalytic efficiencies were higher than that of human aldehyde reductase. Thus, aldose reductase acts not only as a major reductase for isocaproaldehyde formed from steroidogenesis but also as a scavenger of aldehydes derived from lipid peroxidation in mammalian adrenal glands.
Matsuura
K
K
Biochemistry Laboratory, Gifu Pharmaceutical University, Japan.
Deyashiki
Y
Y
Bunai
Y
Y
Ohya
I
I
Hara
A
A
D000311:Adrenal Glands / Q000201:enzymology*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D002208:Caproates / Q000378:metabolism*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D007700:Kinetics; D008322:Mammals; D009281:Naphthalenes / Q000494:pharmacology; D011817:Rabbits; D013045:Species Specificity; D013379:Substrate Specificity
D000447:Aldehydes; D002208:Caproates; D004791:Enzyme Inhibitors; D009281:Naphthalenes; C040550:tolrestat; C018575:isocaproaldehyde; D000449:Aldehyde Reductase; D002786:Cholesterol Side-Chain Cleavage Enzyme