Regulation of rat liver microsomal cholesterol 7 alpha-hydroxylase: presence of a cytosolic activator.
Microsomal cholesterol 7 alpha-hydroxylase (EC 1.14.13.7) in rat liver was assayed by a single-isotope-incorporation method, and factors influencing its activity were studied. Crude cytosol contained a non-catalytic activator which was heat-stable and on-dialyzable. This activator enhanced cholesterol 7 alpha-hydroxylase catalytic activity. The stimulatory property of this cytosolic activator was not altered by cholestyramine feeding, and was retained after fractionation by ammonium sulfate of saturation up to 65%. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) stimulated hydroxylase activity at concentrations up to 90 micro M. ATP at concentration greater than 1.2 mM inhibited hydroxylase activity. NaF was stimulatory at concentrations up to 50 mM with a maximum stimulatory effect at 10 mM, and was antagonistic in effect to ATP. HMG-CoA and ATP at the above inhibitory concentrations and higher abolished the activating effect of the cytosolic factor.
D000214:Acyl Coenzyme A / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology; D002940:Circadian Rhythm; D003600:Cytosol / Q000378:metabolism*; D004789:Enzyme Activation; D007700:Kinetics; D008297:Male; D015093:Meglutol / Q000031:analogs & derivatives / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism*
D000214:Acyl Coenzyme A; D002792:Cholestyramine Resin; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D000255:Adenosine Triphosphate; D012969:Sodium Fluoride; D015093:Meglutol; D013250:Steroid Hydroxylases; D002790:Cholesterol 7-alpha-Hydroxylase