Cholesterol diurnal variations

Shapiro DJ, Rodwell VW 1969 Diurnal variation and cholesterol regulation of hepatic HMG-CoA reductase activity. Biochem Biophys Res Commun 37 867—872 Silver R, LeSauter J, Tresco PA, Lehman MN 1996 A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms. Nature 382 810-813... 

Negative nitrogen balance may occur in blind people, and the serum protein concentration may be reduced. The serum cholesterol is frequently increased, and bilirubin concentration may also exceed the upper limit of normal. The diurnal variation of serum iron is often lost. 

Bremer and Gloor [40] concluded that enzymes for both reactions were present in hepatic microsomes, but recent studies with microsomes of rat [40-42] and human liver [43] have confirmed the presence of only one enzyme, CoA ligase. The assay system, essentially that for long-chain acyl-CoA ligase [42,43], includes 50 mM NaF, a phosphate buffer (pH 7.5), the enzyme preparation, and constituents of Eqn. 1. Product formation was linear up to 12 min with added protein (between 0.1 and 1.2 mg) from a crude microsomal fraction. Sterol carrier protein [44], cysteine or nicotinamide [38,40] were without effect. This rate-limiting enzyme in the two-step sequence catalyzing conjugation of bile acids exhibits a diurnal variation such that the time of maximum enzyme activity coincides with predicted maximum activity of cholesterol 7a-hydroxylase and the time of maximal biosynthesis of bile acids [45]. The enzyme has not been purified. 

Section VI The patterns of diurnal variations in cholesterol synthesis and cholesterol 7a-hydroxylase activity have been found to be practically the... 

In 1-14 weeks after withdrawing treatment bile reverts to its supersaturated state (13). Since other factors (obesity, pregnancy, diurnal variation of biliary cholesterol saturation, presence of nucleating factors, etc.) are required for gallstone recurrence, a supersaturated bile does not necessarily mean gallstone recurrence, but does represent a high risk factor. 

Two types of regulations are important. The diurnal variations in reductase activity are brought about by alterations in the amounts of the enzyme protein and, also, the reductase-specific mRNA. An increase in HMG-CoA reductase appears to be due to an increase in its synthesis while decreases are caused by a cessation of its formation. Several compounds such as oxygenated sterols (but not cholesterol itself) seem to prevent transcription of the reductase gene. Mevalonate (or products of its metabolism), in addition to inhibiting synthesis of the reductase, also appears to enhance its degradation. 

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