Development of Hydrolytic Cholesterol Esterase Activity in Rat Brain<sup>*</sup>

Clarenburg, R; Steinberg, Alan B.; Asling, J. H.; Chaikoff, I.L.

doi:10.1021/bi00871a037

Cited by 24 publications

(6 citation statements)

References 20 publications

(20 reference statements)

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“…The activity pattern of the mammarygland enzyme was thus confirmed to be the inverse of the pattern seen in the liver. Since 60-70% of the cholesterol output into milk is supplied from exogenous sources (Clarenburg & Chaikoff, 1966;Gibbons et al, 1983), from either the liver or the intestine, it should be possible to correlate the variations in mammary-gland HMG-CoA reductase activity with the diurnal variation of the hepatic enzyme (Easom & Zammit, 1984), the food intake of the mothers and the cholesterol synthesized in the gland. In fact, consideration of the cholesterol synthesized in the gland, as determined by Gibbons et al (1983), indicates that HMG-CoA reductase activity only correlates with synthesis of the sterol across the hours of darkness when both the enzyme activity and the cholesterol synthesized in the gland were declining.…”

Section: Discussionmentioning

confidence: 99%

Diurnal variation in the fraction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the active form in the mammary gland of the lactating rat

Smith¹,

Middleton²,

West³

1986

Biochemical Journal

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'Expressed' and 'total' activities of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) were measured in freeze-clamped samples of mammary glands from lactating rats at intervals throughout the 24 h light/dark cycle. 'Expressed' activities were measured in microsomal fractions isolated and assayed in the presence of 100 mM-KF. 'Total' activities were determined in microsomal preparations from the same homogenates but washed free of KF and incubated with exogenously added sheep liver phosphoprotein phosphatase before assay. Both 'expressed' and 'total' activities of HMG-CoA reductase underwent a diurnal cycle, which had a major peak 6 h into the light phase and a nadir 15 h later, i.e. 9 h into the dark period. Both activities showed a secondary peak of activity (around 68% of the maximum activity) at the time of changeover from dark to light, with a trough in the value of the 'expressed' activity that was close to the nadir value. 'Expressed' activity was lower than 'total' at all time points, indicating the presence of enzyme molecules inactivated by covalent phosphorylation. Nevertheless the 'expressed'/'total' activity ratio was comparatively constant and varied only between 43% and 75%. Immunotitration of enzyme activity, with antiserum raised in sheep against purified rat liver HMG-CoA reductase, confirmed the presence of both active and inactive forms of the enzyme and indicated that at the peak and nadir the variation in 'expressed' HMG-CoA reductase activity resulted from changes in the total number of enzyme molecules rather than from covalent modification. The sample obtained after 3 h of the light phase exhibited an anomalously low 'total' HMG-CoA reductase activity, which could be increased when Cl- replaced F- in the homogenization medium. The result suggests that at that time the activity of the enzyme could be regulated by mechanisms other than covalent phosphorylation or degradation.

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Section: Discussionmentioning

confidence: 99%

Diurnal variation in the fraction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the active form in the mammary gland of the lactating rat

Smith¹,

Middleton²,

West³

1986

Biochemical Journal

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“…This is equivalent to 5.15-6.45mg of cholesterol/day for a whole gland weighing 12-15 g (D. H. Williamson, unpublished work) in rats weighing between 250-300g. Clarenburg & Chaikoff (1966) have calculated that a lactating rat of this size secretes 16.0mg of cholesterol into the milk per day. In the steady state, therefore, and assuming equilibration of cholesterol derived from exogenous and endogenous sources, then a maximum of 32.2-40.3% originates from endogenous synthesis within the organ.…”

Section: Site Ofmilk Cholesterol Synthesismentioning

confidence: 99%

“…the rat secretes approx. 16 mg per day in the milk (Clarenburg & Chaikoff, 1966). Unlike the liver, however, the regulation of cholesterol synthesis and uptake in this organ has received relatively little attention.…”

mentioning

confidence: 99%

“…Unlike the liver, however, the regulation of cholesterol synthesis and uptake in this organ has received relatively little attention. Although the lactating gland is capable of converting acetate into cholesterol in vitro (Clarenburg & Chaikoff, 1966;Middleton et al, 1981), the quantity of cholesterol Abbreviation used: HMG-CoA, 3-hydroxy-3methylglutaryl-CoA. synthesized by the gland compared with the liver is unknown.…”

mentioning

confidence: 99%

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Regulation of cholesterol synthesis in the liver and mammary gland of the lactating rat

Gibbons¹,

Pullinger²,

Munday³

et al. 1983

Biochemical Journal

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The activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase; EC 1.1.1.34) in the lactating mammary gland of rats killed between 10:00 and 14:30 h was 2-3 times that in the livers of the same animals. In contrast, after injection of 3H2O in vivo, the rate of appearance of 3H in the cholesterol of the gland was much lower than that in the liver. In the mammary gland of virgin and non-lactating animals, the activity of HMG-CoA reductase was less than 10% of that of the lactating gland. The activity of HMG-CoA reductase in the lactating mammary gland was significantly (P less than 0.005) lower at midnight than at mid-day, and appeared to show an inverse relationship to the activity of the liver enzyme. However, there was no corresponding change in the incorporation of 3H into the gland cholesterol. Withdrawal of food for 6h had no effect on the activity of HMG-CoA reductase in the lactating mammary gland, but resulted in a significant decrease (P less than 0.005) in that of the liver. Starvation of lactating rats for 24h produced a significant decrease (P less than 0.005) in the activity of the enzyme in both organs. There was also a significant decline in the rate at which 3H2O was incorporated in vivo into the cholesterol of both organs (liver, P less than 0.05; gland, P less than 0.005). Giving a high-fat palatable diet together with chow to lactating animals led to a decline in HMG-CoA reductase activity in the mammary gland, but not in liver. This decrease in the gland was not accompanied by a corresponding decline in the apparent rate of cholesterol synthesis.

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“…tion (Adams and Davison, 1959), in the rat brain during 7-10 days of age (Eto and Suzuki, 1972), in the rabbit brain at 17 days of age (Clarenburg et al, 1966), and in the human spinal cord a few weeks before birth and in the corpus callosum a few weeks after birth (Adams and Davison, 1959). These observations have led to the growth of a hypothesis (Eto and Suzuki, 1972) that cholesterol esters might somehow be related to myelination.…”

Section: H K M Yusuf Et a Lmentioning

confidence: 99%

Cholesterol Esters of the Human Brain During Fetal and Early Postnatal Development: Content and Fatty Acid Composition

Yusuf

Dickerson

Hey

et al. 1981

Journal of Neurochemistry

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The content and fatty acid composition of cholesterol esters of the human brain during development from 13 weeks' gestation up to 26 months of age was studied. The three major brain areas, the forebrain, cerebellum, and the brain stem, were studied separately. The concentration of the esters in each brain region was the highest at the earliest fetal age of 13 weeks and fell during growth. However, transient rises in the concentration were observed, at about birth in the forebrain and at 4–5 months after birth in the cerebellum The peak concentration during the transient period (125–150 μg/g fresh tissue of forebrain and 100–125 μg/g of cerebellum) was similar to the concentrations observed in the two parts respectively during early fetal ages. The brain stem also showed similar transient peak at about a few weeks before birth, but only when the esters were expressed as amount per cell. In absolute terms, a clear transient period was evident in the forebrain between birth and 9 months, while in the cerebellum or the brain stem, the total amount of the esters increased up to about 1 year of age and then remained almost unchanged. The major fatty acids of the esters were palmitic, palmitoleic, stearic, oleic, linoleic and arachidonic acid. Most of these fatty acids showed certain changes in relative proportions during development. Thus, in the forebrain, palmitic and oleic acid decreased from about 32% and 40% (weight percentages) at 13–15 weeks of gestation to about 20% and 25% respectively at 26 months of age. During this period, linoleic and arachidonic acid increased from about 3% and S% to about 10% and 24%, respectively. Most of these changes occurred after birth. The cerebellum and the brain stem differed only slightly from the forebrain in either the fatty acid composition or the pattern of the developmental changes in the composition.

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Development of Hydrolytic Cholesterol Esterase Activity in Rat Brain^*

Cited by 24 publications

References 20 publications

Diurnal variation in the fraction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the active form in the mammary gland of the lactating rat

Diurnal variation in the fraction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the active form in the mammary gland of the lactating rat

Regulation of cholesterol synthesis in the liver and mammary gland of the lactating rat

Cholesterol Esters of the Human Brain During Fetal and Early Postnatal Development: Content and Fatty Acid Composition

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Development of Hydrolytic Cholesterol Esterase Activity in Rat Brain*

Cited by 24 publications

References 20 publications

Diurnal variation in the fraction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the active form in the mammary gland of the lactating rat

Diurnal variation in the fraction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the active form in the mammary gland of the lactating rat

Regulation of cholesterol synthesis in the liver and mammary gland of the lactating rat

Cholesterol Esters of the Human Brain During Fetal and Early Postnatal Development: Content and Fatty Acid Composition

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Development of Hydrolytic Cholesterol Esterase Activity in Rat Brain^*