The UTILIZATION OF Β-Hydroxy-Β-Methyl-Δ-Valerolactone IN CHOLESTEROL BIOSYNTHESIS

Tavormina, Peter A.; Gibbs, Margaret; Huff, Jesse W.

doi:10.1021/ja01598a089

Cited by 203 publications

(48 citation statements)

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“…The data in this study confirmed that first-order kinetics characterized the metabolism of [14C]mevalonate to GO2 over at least a 17-h period and furthermore, that the values calculated from 9-h G4CO2 collections predicted values experimentally observed during the 17-h collection for the male and female subject studied: male calculated 17-h value, 3.89 x 106 dpm; observed 17-h value, 3.69 x 106 dpm; female calculated 17-h value, 4.39 x 106 dpm; observed 17-h value, 4.50 x 106 dpm.…”

Section: Methodssupporting

confidence: 85%

See 1 more Smart Citation

Sex difference in human mevalonate metabolism.

Feingold¹,

Wiley²,

Searle³

et al. 1980

J. Clin. Invest.

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Section: Methodssupporting

confidence: 85%

“…Mevalonic acid is an essential intermediate in the synthesis of both plant and animal sterols (3,4). The further finding that the primary feedback control of cholesterogenesis is located at the site of mevalonate synthesis (5)(6)(7)(8) has stimulated an intense interest in the metabolic fate of this cholesterol precursor.…”

Section: Introductionmentioning

confidence: 99%

Sex difference in human mevalonate metabolism.

Feingold¹,

Wiley²,

Searle³

et al. 1980

J. Clin. Invest.

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“…There is now abundant evidence that mevalonic acid is an essential intermediate in the synthesis of all animal and plant sterols (1,2). In addition, previous studies from this laboratory have established that the reaction responsible for the synthesis of mevalonate represents the primary site of feedback control of cholesterol biosynthesis (3,4), a finding that has been confirmed by a number of subsequent reports (5)(6)(7).…”

Section: Introductionmentioning

confidence: 73%

Studies of the In Vivo Metabolism of Mevalonic Acid in the Normal Rat

Hellström¹,

Siperstein²,

Bricker³

et al. 1973

J. Clin. Invest.

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A B S T R A C T Studies were performed to examine synthesis, tissue localization, and metabolism of mevalonic acid in normal rats. Circulating mevalonate was found to have a rapid turnover phase of 5 min and a slower phase of 40-50 min. Under in vitro conditions the synthesis of mevalonate is carried out most actively by the liver and only to a minor extent by the other tissues studied. The most unexpected finding of this study was that both in vivo and in vitro the kidneys rather than the liver are the primary site of the metabolism of circulating mevalonate. Whereas mevalonate in the liver is rapidly transformed to cholesterol, the major products of mevalonate metabolism in the renal tissues during the same time period are squalene and lanosterol. Exogenous in contrast to circulating mevalonate is metabolized primarily in the intestine.

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“…This suggests that the site of disturbance exists in the process between acetyl CoA and mevalonic acid. The rate limiting step in this metabolism is from HMG-CoA to mevalonic acid (Tavarmina et al 1956;Goldfarb 1978) and therefore, probably L-asparaginase suppresses this step. This step is carried out in the microsomal fraction, and protein synthesis, which is inhibited by L-asparaginase, is also performed in the microsome fraction.…”

Section: Resultsmentioning

confidence: 99%

The effect of L-asparaginase on cholesterol biosynthesis.

Takeda

Matsuura

1981

Tohoku J. Exp. Med.

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The liver from the Wistar rat was incubated either in the solution of 1 µCi acetate-1-14C or 0.1 µCi mevalonic acid-2-14C, and incorporations of radioactivity to phospholipid and cholesterol were estimated respectively. The incorporation of labeled acetate to cholesterol in the L-asparaginase-treated rat was significantly lower than that in the controls. However, there were no differences of the incorporation into the mevalonic acid between the study group and the controls. These results suggest that the inhibitory mechanism may exist between the steps of acetate and mevalonic acid.L-asparaginase; cholesterol biosynthesis; acute lymphocytic leukemiaSince the first report of successful L-asparaginase treatment of acute lymphocytic leukemia and malignant lymphoma (Oettgen et al. 1967) the clinical evaluation of this drug has been established. There, various side effects of the drug were also described. Among these, the decrease in serum lipids, especially cholesterol, is the most remarkable one . The serum protein decreases by L-asparaginase, which may be due to the suppression of protein biosynthesis (Bettigole et al. 1970). However, the cause of the change in cholesterol level was not clearly understood. The decrease in cholesterol may be derived from the disturbances of cholesterol synthesis or the acceleration of cholesterol catabolism and another possibility may be depending upon the decrement of lipoprotein, which works as a carrier of cholesterol. To know whether L-asparaginase influences the cholesterol biosynthesis, we carried out the following studies. MATERIALS AND METHODSMale Wistar rats weighing 150-200 g were used. L-Asparaginase (Kyowa Hakko Co.) was injected intravenously in a single dose of 2000 TI/kg. The rats were anesthetized with ether and the abdominal cavity was explored. Soon after exsanguination from the abdominal aorta, the liver was exstirpated and was sliced with a hand slicer. The liver slices were incubated in an oxygen filled flask with culture medium, which was put on a shaker at 37°C for 90 min. 0.25 g of the liver slices was weighed and incubated in 3 ml of phosphate buffer (pH 7.2) with 0.3 ml substrate (30 µmoles Na acetate+1 µCi acetate-1-14C or 0.1 µCi mevalonic acid-2-'4C). Filter paper dipped in 2 N NaOH was used for CO2 absorption, instead of using 1 M Hyamin in methanol solution which brought about

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The UTILIZATION OF Β-Hydroxy-Β-Methyl-Δ-Valerolactone IN CHOLESTEROL BIOSYNTHESIS

Cited by 203 publications

References 0 publications

Sex difference in human mevalonate metabolism.

Sex difference in human mevalonate metabolism.

Studies of the In Vivo Metabolism of Mevalonic Acid in the Normal Rat

The effect of L-asparaginase on cholesterol biosynthesis.

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