Activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in brains of adult and 7-day-old rats

Abstract

Rat brain contains 3-hydroxy-3-methylglutaryl-CoA reductase activity, but this enzyme is far more active in 7-day-old brain than in adult brain. This difference may partly explain why cholesterol biosynthesis is more rapid in growing than in adult rat brain.

Rat Brain 3‐Hydroxy‐3‐Methylglutaryl‐CoA Reductase: Subcellular Distribution and Cold Lability

“…Further studies were therefore carried out on the 22-day-old rat brain. It is worth noting however, that our result is consistent with the finding of Sudjik and Booth (1976) that the activity of this enzyme in brain declines with age of the animal.…”

“…The latency of mitochondrial HMG-CoA reductase and subcellular distribution data (Table 2) suggest that the activity, referred to as being associated with the rapidly sedimentable fraction of rat brain homogenate by Sudjik and Booth (1976) and Aragon et al (1978). is in fact located in the mitochondria.…”

“…The mammalian brain enzyme however, has been studied mainly from the developmental viewpoint and exhibits a peak of activity in the rat brain at about 10 days after birth (Sudjik and Booth, 1976;Aragon et al, 1978) with a decline in activity with age. This pattern of activity correlates well with the developmental pattern of myelination as reported for the rat brain (Dobbing and Sands, 1971).…”

“…This pattern of activity correlates well with the developmental pattern of myelination as reported for the rat brain (Dobbing and Sands, 1971). Whilst the brain enzyme has been reported to have qualitatively the same feedback inhibitory characteristics as the liver enzyme (Volpe and Hennessy, 1977), its sub-cellular distribution appears to be different, two-thirds of the total brain activity being microsomal and the rest being associated with a 'rapidly sedimentable' fraction of the cell (Sudjik and Booth, 1976;Aragon et al, 1978). This report provides evidence that the localisation of the rapidly sedimentable fraction of HMG-CoA reductase in the rat brain is mitochondria1 and that the total brain enzyme exhibits both cold lability and diurnal rhythmicity, in common with the hepatic enzyme.…”

Changes in sterol biosynthesis accompanying cessation of glial cell growth in serum-free medium

“…Since cholesterol carried by plasma lipoproteins does not cross the blood/brain barrier in appreciable quantities (McIlwain & Bachelard, 1971;Pardridge & Mietus, 1980), neural cells apparently must rely on cholesterol synthesized in situ for the formation of new membranes. This hypothesis is supported by the data of Kandutsch & Saucier (1969), which demonstrate a high rate of sterol synthesis de novo from [14Clacetate in the Several studies have shown that the activity of HMG-CoA reductase, which is generally regarded as the rate-limiting enzyme in the cholesterol biosynthetic pathway in mammalian tissues and cultured cells (for review see Volpe, 1978), is elevated in developing brain (Kandutsch & Saucier, 1969;Sudjic & Booth, 1976;Aragon et al, 1978;Maltese & Volpe, 1979a;Ness et al, 1979). However, a report of high cytosolic HMG-CoA synthase activity in developing rat brain has raised the possibility that enzymes proximal to the reductase may be involved in the regulation of sterol synthesis in neural tissues (Shah, 1978).…”