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Inhibition of Human Brain Aldose Reductase and Hexonate Dehydrogenase by Alrestatin and Sorbinil
Author(s) -
O'Brien Margaret M.,
Schofield Philip J.,
Edwards Michael R.
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb07964.x
Subject(s) - sorbinil , aldose reductase , aldose reductase inhibitor , aldehyde reductase , uncompetitive inhibitor , chemistry , biochemistry , dehydrogenase , enzyme , non competitive inhibition
Human brain aldose reductase and hexonate dehydrogenase are inhibited by alrestatin (AY 22,284) and sorbinil (CP 45,634). Inhibition by alrestatin is noncompetitive for both enzymes, and slightly stronger for hexonate dehydrogenase ( K I values 52‐250 μ M ) than for aldose reductase ( K I values 170‐320 μ M ). Sorbinil inhibits hexonate dehydrogenase far more potently than aldose reductase, K I values being 5 μ M for hexonate dehydrogenase and 150 μ M for aldose reductase. The inhibition of hexonate dehydrogenase by sorbinil is noncompetitive with respect to both aldehyde and NADPH substrates, and is thus kinetically similar to the inhibition by alrestatin. However, sorbinil inhibition of aldose reductase is uncompetitive with respect to glyceraldehyde and noncompetitive with NADPH as the varied substrate. Inhibition of human brain aldose reductase by these two inhibitors is much less potent than that reported for the enzyme from other sources.