Mechanism and stereochemistry in the sequential enzymatic saturation of the two double bonds in cholesta-4,6-dien-3-one.
The mechanism and stereochemistry in connection with enzymatic conversion of cholesta-4,6-dien-3-one into cholestanol was studied. Rat and mouse liver microsomes are able to catalyze NADPH-dependent sequential saturation of the two double bonds. Evidence was obtained that the saturation of the delta 6-double bond includes transfer of a hydride ion from the B-side of the cofactor to the 7-position of the steroid (mainly 7 beta-position), followed by addition of a proton to the 6 alpha-position (mainly trans addition). The saturation of the delta 4-double bond includes transfer of a hydride ion from the B-side of the cofactor to the 5 alpha-position of the steroid followed by addition of a proton to the 4 beta-position (trans addition). The reduction of the 3-oxo group was found to involve transfer of a hydride ion from the B-side of the cofactor NADPH to the 3 alpha-position of the steroid. The results are in accord with the contention that the enzymatic saturation of the two double bonds involves a polarization of the 3-oxo group making C-7 electrophilic and C-6 nucleophilic in connection with the saturation of the delta 6-double bond and C-5 electrophilic and C-4 nucleophilic in connection with the saturation of the delta 4-double bond.
Björkhem
I
I
Department of Clinical Chemistry, Huddinge Hospital, Sweden.
Buchmann
M
M
Byström
S
S
D000818:Animals; D002384:Catalysis; D004083:Cholestanol / Q000378:metabolism*; D002783:Cholestenones / Q000737:chemistry*; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism
D002783:Cholestenones; D009249:NADP; C030311:4,6-cholestadien-3-one; D004083:Cholestanol