Absence Of Diurnal Rhythm Research Articles

Studies on the diurnal rhythm of mevalonate metabolism by sterol and nonsterol pathways and of mevalonate-activating enzymes

1. 1. Both in vivo and in vitro incorporation of mevalonic acid into nonsaponifiable lipids by 17-day-old chick liver and kidney did not show diurnal rhythm. 2. 2. Using 14CO 2 production from MVA as an index of the shunt pathway not leading to sterols, we have demonstrated for the first time that there is no diurnal rhythm in this pathway. 3. 3. No significant differences were found in the specific activities of mevalonate kinase, mevalonate-5-phosphate kinase and mevalonate-5-pyrophosphate decarboxylase from chick liver and kidney throughout a period of 24 hr, using [1- 14C]mevalonate as substrate. 4. 4. The absence of diurnal rhythm in the decarboxylase activity was corroborated by further experiments carried out using [2- 14C]mevalonate-5-pyrophosphate as specific substrate of this enzyme.

Control of cholesterol synthesis in hepatomas: Absence of diurnal rhythm in hepatomas 7794A and 9618A

We have examined the Morris hepatomas 7794A and 9618A for the presence of a diurnal variation in cholesterol synthesis such as is observed in the livers of normal rats. Whereas the livers of the tumour-bearing animals showed a 3–5 fold increase in rate of cholesterol synthesis from acetate between midday and midnight, no such increase occurred in the hepatomas. Furthermore, adrenalectomy resulted in a 3-fold increase in cholesterol synthesis (as measured at midday) in the host liver, but not in hepatoma 7794A. Work by others has indicated that diurnal variations in cholesterol synthesis in normal liver are due to variations in the amount rather than in the specific activity of the ratecontrolling enzyme of the cholesterogenic pathway, namely β-hydroxy-β-methylglutaryl co-enzyme A reductase. Our work has now demonstrated that at least two of the “minimal-deviation” hepatomas exhibit a defect in control over the synthesis and/or degradation of this enzyme, i.e. in addition to the defective “feedback” control of its activity that has been shown in many previous reports.