Substrate specificity of mouse aldo-keto reductase AKR7A5.
We have determined the substrate specificity of a mouse aldo-keto reductase (AKR) AKR7A5, an enzyme that is similar to rat aflatoxin aldehyde reductase (AKR7A1) and to human brain succinic semialdehyde reductase (AKR7A2). Previously, we have shown that the mouse enzyme is present in a range of tissues including liver, kidney, testis and brain, and is able to reduce several carbonyl compounds, including succinic semialdehyde, 2-carboxybenzaldehyde, 4-nitrobenzaldehyde and 9,10-phenanthrenequinone [FEBS Lett. 523 (2002) 213]. It has been suggested that it may represent the mouse equivalent of human succinic semialdehyde reductase which is responsible for the biosynthesis of gamma-hydroxybutyrate. In this study, we show that the enzyme is also able to reduce other aromatic aldehydes such as 4-chloro-3-nitrobenzaldehyde, and 3-nitrobenzaldehyde, and has particular high specific activity towards dicarbonyls such as acenapthenequinone, 2,3-bornanedione (camphorquinone), and phenylglyoxal. It has low specific activity towards ketones, and alpha,beta-unsaturated carbonyls such as acrolein and 4-hydroxynonal. The enzyme is inhibited by several compounds including quercitin, ethacrynic acid, indomethacin and sodium valproate. Developing selective inhibitors may lead to a means of modifying the activity of the enzyme in vivo.
Hinshelwood
Alison
A
Department of Pharmaceutical Sciences, University of Strathclyde, 204 George Street, G1 1XW, Glasgow, UK.
McGarvie
Gail
G
Ellis
Elizabeth M
EM
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C000614209:AKR7A5 protein, mouse