TY - JOUR
T1 - Regulation of cholesterol synthesis in rat adrenal gland through coordinate control of 3 hydroxy 3 methylglutaryl coenzyme A synthase and reductase activities
AU - Balasubramaniam, S.
AU - Goldstein, J. L.
AU - Brown, M. S.
PY - 1977
Y1 - 1977
N2 - The activities of cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase [3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating), EC 4.1.3.5] and microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase [mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34], 2 sequential enzymes in the cholesterol biosynthetic pathway, were shown to be regulated coordinately in the adrenal gland of the rat. When the plasma cholesterol level was lowered by administration of 4-aminopyrazolopyrimidine, a treatment known to enhance cholesterol synthesis in the adrenal gland, synthase activity in the gland rose by 14 to 29 fold and reductase activity rose by 50 to 100 fold. The subsequent intravenous infusion of low density lipoprotein restored the plasma cholesterol level and suppressed synthase and reductase activities in parallel. The activities of adrenal 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase were also shown to exhibit a coordinate pattern of diurnal variation with peaks in both enzymes achieved at the mid point of the dark cycle. The activity of adrenal acetoacetyl coenzyme A thiolase (acetyl CoA acetyltransferase; acetyl-CoA:acetyl-CoA C-acetyltransferase, EC 2.3.1.9), the enzyme preceding the synthase in the cholesterol biosynthetic pathway, and the activity of adrenal mevalonate kinase (ATP:mevalonate 5-phosphotransferase, EC 2.7.1.36), the enzyme following the reductase, were not enhanced by cholesterol deprivation, and neither exhibited a pattern of diurnal variation. The coordinate control of 3 hydroxy-3-methylglutaryl CoA synthase and reductase in rat adrenal gland provides a model system to study the biochemical mechanisms for the regulation of cholesterol synthesis in a tissue that uses cholesterol for the synthesis of steroid hormones.
AB - The activities of cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase [3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating), EC 4.1.3.5] and microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase [mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34], 2 sequential enzymes in the cholesterol biosynthetic pathway, were shown to be regulated coordinately in the adrenal gland of the rat. When the plasma cholesterol level was lowered by administration of 4-aminopyrazolopyrimidine, a treatment known to enhance cholesterol synthesis in the adrenal gland, synthase activity in the gland rose by 14 to 29 fold and reductase activity rose by 50 to 100 fold. The subsequent intravenous infusion of low density lipoprotein restored the plasma cholesterol level and suppressed synthase and reductase activities in parallel. The activities of adrenal 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase were also shown to exhibit a coordinate pattern of diurnal variation with peaks in both enzymes achieved at the mid point of the dark cycle. The activity of adrenal acetoacetyl coenzyme A thiolase (acetyl CoA acetyltransferase; acetyl-CoA:acetyl-CoA C-acetyltransferase, EC 2.3.1.9), the enzyme preceding the synthase in the cholesterol biosynthetic pathway, and the activity of adrenal mevalonate kinase (ATP:mevalonate 5-phosphotransferase, EC 2.7.1.36), the enzyme following the reductase, were not enhanced by cholesterol deprivation, and neither exhibited a pattern of diurnal variation. The coordinate control of 3 hydroxy-3-methylglutaryl CoA synthase and reductase in rat adrenal gland provides a model system to study the biochemical mechanisms for the regulation of cholesterol synthesis in a tissue that uses cholesterol for the synthesis of steroid hormones.
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U2 - 10.1073/pnas.74.4.1421
DO - 10.1073/pnas.74.4.1421
M3 - Article
C2 - 16260
AN - SCOPUS:0017357697
SN - 0027-8424
VL - 74
SP - 1421
EP - 1425
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -