By Rodolfo Paoletti, Dr. David Kritchevsky
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Additional info for Advances in lipid research. / Volume 14
Nadir levels are, however, initially higher (Fig. 14). C. C H A N G E S T H A T F O L L O W W E A N I N G The changes in reductase activity that occur during development are too large to be attributed to changes in the amplitude or phase of the diurnal rhythm. The 5- to 10-fold rhythmic change in adult rats is dwarfed by the increase in activity that follows weaning (Fig. 15). For rats weaned 21 days after birth, the nadir activity rises 70-fold from noon on day 22 to noon on day 24. The overall increase in activity from noon (nadir) to midnight (peak) on day 22 is even larger and represents a doubling of reductase activity every 110 minutes.
1973) and hepatic (Krzemien and Haven, 1974) microsomes. E. SUMMARY At present, there is reliable evidence for modulation of reductase activity both in vivo and in vitro, b u t there is little or no evidence that establishes their mechanism, or their relationship to each other and to physiological control processes. Determining how the in vitro processes of activation and inactivation relate to the in vivo effects of hormones and diet will b e an interesting and important subject for future research.
Initially, the effects on HMG-CoA reductase were attributed to inhibition or stimulation of its catalytic activity. That this interpretation might require revision was suggested by the discovery that the increases and decreases in HMG-CoA reductase activity which characterize the rhythm arise from synthesis and degradation of reductase protein. This suggested that various effectors might also act by altering the rates of synthesis or degradation of reductase protein. Rapid synthesis of HMG-CoA reductase protein was first suggested by the ability of inhibitors of protein synthesis to block the diurnal (O) (measured in the 5000 g supernatant fraction) and of HMG-CoA reductase activity ( · ) (measured in the microsomal fraction) were determined in liver homogenates from rats killed at the indicated times.
Advances in lipid research. / Volume 14 by Rodolfo Paoletti, Dr. David Kritchevsky