Old Yellow enzyme: aromatization of cyclic enones and the mechanism of a novel dismutation reaction.
The origin of charge transfer bands that develop on reaction of Old Yellow Enzyme with alpha,beta-unsaturated cyclic ketones such as 3-oxodecalin-4-ene (ODE, numbered according to the convention for steroids), 3-oxodecalin-4-ene-10-carboxaldehyde (ODEC), and 2-cyclohexenone is shown to be due to the aromatization of ODE and ODEC to 3-hydroxy-6,7,8,9-tetrahydronaphthalene (HTN) and of 2-cyclohexenone to phenol. The aromatization of ODEC to HTN is stereospecific and involves the trans dehydrogenation of the 1 beta, 2 alpha hydrogens. The aromatization occurs under aerobic as well as anaerobic conditions. With the exception of ODEC under aerobic conditions, the aromatization of these substrates is accompanied by a dismutation reaction in which the olefinic bond of a second molecule of each substrate is reduced to give the saturated cyclic ketone. Molecular oxygen may serve as the electron acceptor with ODEC and some other substrates under aerobic reaction conditions. The dismutation reaction involves an overall sequence of hydride transfer from one substrate molecule to the beta-carbon of a second substrate molecule along with a solvent proton uptake by the alpha-carbon. 19-Nortestosterone is aromatized to beta-estradiol; however, other 3-oxo-delta 4-steroids such as progesterone, testosterone, and androstene-3,17-dione bind tightly to the enzyme but are not aromatized. The NADPH-dependent reduction of the olefinic bond of alpha,beta-unsaturated carbonyl compounds is limited to aldehydes and ketones. alpha,beta-Unsaturated acids, esters, amides, and nitriles are not reduced. The reduction of the olefinic bond of ODE or cinnamaldehyde by NADPH occurs by an overall sequence of hydride transfer from the reduced pyridine nucleotide to the beta-carbon of the alpha,beta-unsaturated carbonyl compound and a solvent proton uptake by the alpha-carbon. The 4-pro-R hydride of NADPH is transferred in the reduction reaction. Structure-function relationships in the NADPH-dependent reduction of alpha,beta-unsaturated aldehydes or ketones indicate that increasing alkyl substitution at the beta-carbon results in marked decrease in the rate of reduction of the olefinic bond, consistent with a steric hindrance to hydride transfer at the beta-carbon.
Vaz
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AD
Department of Biological Chemistry, Medical School, University of Michigan, Ann Arbor 48109, USA.
Chakraborty
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S
Massey
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D000171:Acrolein / Q000031:analogs & derivatives / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003512:Cyclohexanones / Q000378:metabolism*; D003903:Deuterium; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D008401:Gas Chromatography-Mass Spectrometry; D007659:Ketones / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009249:NADP / Q000494:pharmacology; D009252:NADPH Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013764:Tetrahydronaphthalenes / Q000378:metabolism*
C092886:3-oxodecalin-4-ene; C090506:3-oxodecalin-4-ene-10-carboxaldehyde; D000447:Aldehydes; D003512:Cyclohexanones; D007659:Ketones; D013764:Tetrahydronaphthalenes; C028215:2-cyclohexen-1-one; D009249:NADP; D000171:Acrolein; D003903:Deuterium; D009252:NADPH Dehydrogenase; C012843:cinnamaldehyde