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EC number: 212-855-9
CAS number: 873-94-9
- QSAR study: Only monoalcohols were inhibitory:
cis-3,3,5-trimethylcyclohexanol 61.1 % (p<0.001)
trans-3,3,5-trimethylcyclohexanol 59.1 % (p<0.01)
cyclohexanol 58.3 % (p<0.05)
1-methylcyclohexanol 54.9 % (p<0.05)
3-methylcyclohexanol 50.6 % (insign.)
cyclopentanol 36.8 % (insign.)
3,3,5-cyclohexanone 25.0 % (insign.)
cyclohexane-1,2-diol 21.5 % (insign.)
cyclohexane-1,3-diol 14.6 % (insign.)
cyclohexane-1,4-diol 14.5 % (insign.)
tetrahydropyran 9.4 % (insign.)
cyclohexane 5.0 % (insign.)
- Effect of redox state: When the NADH/NAD ratio was increased by starvation,
the effect of cyclohexanols on reductase activity was still found
(64 % inhibition by cyclohexanol compared to starved controls, p<0.05).
- Dose dependence: The inhibition of HMGCoA reductase increased with
administered dose up to a maximum, which was 70 % at 3 mmol/kg bw in the
case of 3,3,5-trimethylcyclohexanol.
- Time course: Upon administration of 3 mmol 3,3,5-trimethylcyclohexanol/kg bw
and sacrifice at various times, enzyme inhibition began 6-8 hours after
dosing and was maintained until about 40 hours after dosing.
- Lipid synthesis rate study: 47 % inhibition (P<0.01) of 3H incorporation
into digitonin precipitable sterol (DPS) 17 hours after dosing with
- Mechanism: The inhibition of HMGCoA reductase appears to be due to decreased
synthesis of HMGCoA reductase in liver following an initial acute effect in
the degree of phosphorylation of the enzyme.
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