PMID- 3768035
OWN - NLM
STAT- MEDLINE
DCOM- 19861119
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 35
IP  - 20
DP  - 1986 Oct 15
TI  - Cyclohexanol and methylcyclohexanols. A family of inhibitors of hepatic HMGCoA 
      reductase in vivo.
PG  - 3489-94
AB  - Oral dosing of rats with cyclohexanol and methylcyclohexanols resulted in the 
      inhibition of hepatic HMGCoA reductase. Neither cyclohexane or cyclohexane diols 
      exerted any effects. Inhibition was not due to alcohol dehydrogenase mediated 
      changes in redox state since 3,3',5-trimethylcyclohexanol (TMC), a non substrate 
      for alcohol dehydrogenase, was a potent inhibitor of HMGCoA reductase. Following 
      a single dose of TMC there was no alteration in total hepatic HMGCoA reductase 
      activity for more than 6 hr after which the enzyme activity was depressed in a 
      dose-dependent manner. The normal diurnal rhythm of HMGCoA reductase was reduced 
      in amplitude following TMC administration but the phase was unaltered and the t 
      1/2 for activity decay following the peak of activity was unaffected. Prior to 
      the inhibitory effect of a TMC dose becoming apparent in total HMGCoA reductase 
      activity we found that the expressed activity of the enzyme (after isolation in 
      F- medium to suppress endogenous protein phosphatase) was depressed by 43%. The 
      inhibitory effect of TMC on total HMGCoA reductase activity seen 8 hr or more 
      after dosing was reflected by inhibition of sterol synthesis in liver measured in 
      vivo after [3H]-H2O administration.
FAU - Miciak, A
AU  - Miciak A
FAU - White, D A
AU  - White DA
FAU - Middleton, B
AU  - Middleton B
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Cyclohexanols)
RN  - 0 (Fatty Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Sterols)
RN  - 08CL3G94GH (3,3,5-trimethylcyclohexanol)
SB  - IM
MH  - Animals
MH  - Cyclohexanols/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Fatty Acids/biosynthesis
MH  - *Hydroxymethylglutaryl-CoA Reductase Inhibitors
MH  - Liver/*enzymology
MH  - Male
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Starvation/enzymology
MH  - Sterols/biosynthesis
MH  - Time Factors
EDAT- 1986/10/15 00:00
MHDA- 1986/10/15 00:01
CRDT- 1986/10/15 00:00
PHST- 1986/10/15 00:00 [pubmed]
PHST- 1986/10/15 00:01 [medline]
PHST- 1986/10/15 00:00 [entrez]
AID - 0006-2952(86)90616-7 [pii]
AID - 10.1016/0006-2952(86)90616-7 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1986 Oct 15;35(20):3489-94. doi: 10.1016/0006-2952(86)90616-7.