Different Developmental Patterns of 3-Hydroxy-3-Methylglutaryl-CoA Reductase in Chick Tissues according to Their Role in Cholesterogenesis

Abstract

The developmental pattern of microsomal 3-hydroxy-3-methylglutaryl-CoA reductase activity was different in liver, intestine and brain of neonatal chicks. Hepatic reductase activity sharply increased between 5 and 9 days after hatching. This pattern agrees with changes in acetate incorporation into non-saponifiable lipids by liver slices. Both enzyme activity and acetate incorporation seem to be related to the hepatic uptake of cholesterol from the yolk sac during the first days after hatching and to the new synthesis of cholesterol commencing in the second week. Changes in intestinal reductase suggest that the enzyme was less sensitive to the cholesterol in yolk sac. Brain reductase did not change within the age assayed (1–15 days), being independent from the levels of yolk sac or serum cholesterol during the later steps of myelination.

Effect of Dietary Cholesterol and Cholestyramine on Developmental Pattern of 3-Hydroxy-3-Methylglutaryl-CoA Reductase

“…Changes in the hepatic reductase from control chicks may be explained by the regression of the yolk sac about 5 days after hatching. Like wise, the increase observed from the first day in the intestinal reductase may be explained as a response to the sudden dietary change associated to hatching [1], In both cases, sup plementation of the diet with 2% cholesterol practically suppressed the reductase activity in agreement with the feedback control of cholesterogenesis at the site of the reaction catalyzed by this enzyme [26], The decrease observed in the intestinal reductase from both control and cholestyramine-treated ani mals after 11 days of age does not necessarily reflect a lower enzyme activity, as a high pro portion of noncholesterogenic muscle tissue is present in the samples of this age [1],…”

“…Other details of assay conditions have been reported elsewhere [ 1 ]. Reductase activity was expressed as picomoles of mevalonic acid synthe sized per minute per milligram protein.…”

Research Communications

“…Protein concentration was determined by the method of Lowry et al 31 using bovine albumin as a standard. HMG-CoA reductase activity was measured essentially as described by Shapiro et 28 Three experiments with pools of six animals were performed in each case. Triplicate determinations were carried out in each experiment.…”

“…27 Because of these considerations, we studied the comparative influence of diet supplementation with saturated fatty acids (coconut oil), without or with added cholesterol, and of n-3 PUFA (menhaden oil) on the plasma and liver lipid composition during the neonatal development of chick. Bearing in mind the uncertainty regarding the effect of dietary fat quality on endogenous cholesterol synthesis and the postnatal changes in chick liver 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, 28 the main regulatory enzyme of cholesterogenesis, we also studied the effect of the same dietary treatments on hepatic cholesterol synthesis by measurement of this microsomal enzyme activity.…”