Abstract
We tested the hypothesis that the rate of cholesterol synthesis in tissues determines the concentrations of mevalonic acid (MVA) in plasma. We found that plasma MVA concentrations were correlated (i) with increased rates of whole-body cholesterol synthesis (measured by sterol-balance methods) in patients treated with cholestryamine resin (ii) with decreased rates of whole-body sterol synthesis (indicated by conversion of labeled acetate to sterol in freshly isolated mononuclear leukocytes) in out-patients after 4 weeks on a cholesterol-rich diet. In addition, a diurnal rhythm of plasma MVA concentrations was observed in patients whose activities were strictly controlled on a metabolic ward. At the peak of the rhythm (between midnight and 3 a.m.) MVA concentrations were 3-5 times greater than at the nadir (between 9 a.m. and noon). Furthermore, a relationship between the diurnal rhythm of plasma MVA and endogenous cholesterol synthesis is suggested by our finding that the plasma MVA rhythm was suppressed by cholesterol feeding (1,200 mg/day) and abolished by a 12-day fast. The presence in human plasma of MVA, an obligate precursor of cholesterol, in amounts apparent related to the rate of cholesterol synthesis offers a noninvasive, nonisotopic method for studying cholesterol synthesis in man.
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- Bronzert T. J., Brewer H. B., Jr New micromethod for measuring cholesterol in plasma lipoprotein fractions. Clin Chem. 1977 Nov;23(11):2089–2098. [PubMed] [Google Scholar]
- Brunengraber H., Weinstock S. B., Story D. L., Kopito R. R. Urinary clearance and metabolism of mevalonate by the isolataed perfused rat kidney. J Lipid Res. 1981 Aug;22(6):916–920. [PubMed] [Google Scholar]
- Grundy S. M., Ahrens E. H., Jr, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res. 1969 May;10(3):304–315. [PubMed] [Google Scholar]
- Hagenfeldt L., Hellström K. Blood concentration and turnover of circulating mevalonate in the rat. Life Sci II. 1972 Jul 8;11(13):669–676. doi: 10.1016/0024-3205(72)90016-1. [DOI] [PubMed] [Google Scholar]
- Higgins M., Rudney H. Regulation of rat liver beta-hydroxy-beta-methylglutaryl-CoA reductase activity by cholesterol. Nat New Biol. 1973 Nov 14;246(150):60–61. doi: 10.1038/newbio246060a0. [DOI] [PubMed] [Google Scholar]
- Kopito R. R., Brunengraber H. (R)-mevalonate excretion in human and rat urines. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5738–5740. doi: 10.1073/pnas.77.10.5738. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu G. C., Ahrens E. H., Jr, Schreibman P. H., Samuel P., McNamara D. J., Crouse J. R. Measurement of cholesterol synthesis in man by isotope kinetics of squalene. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4612–4616. doi: 10.1073/pnas.72.11.4612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McNamara D. J., Davidson N. O., Fernandez S. In vitro cholesterol synthesis in freshly isolated mononuclear cells of human blood: effect of in vivo administration of clofibrate and/or cholestyramine. J Lipid Res. 1980 Jan;21(1):65–71. [PubMed] [Google Scholar]
- McNamara D. J., Davidson N. O., Samuel P., Ahrens E. H., Jr Cholesterol absorption in man: effect of administration of clofibrate and/or cholestyramine. J Lipid Res. 1980 Nov;21(8):1058–1064. [PubMed] [Google Scholar]
- Miettinen T. A. Serum squalene and methyl sterols as indicators of cholesterol synthesis in vivo. Life Sci. 1969 Jul 15;8(14):713–721. doi: 10.1016/0024-3205(69)90007-1. [DOI] [PubMed] [Google Scholar]
- Nestel P. J., Poyser A. Changes in cholesterol synthesis and excretion when cholesterol intake is increased. Metabolism. 1976 Dec;25(12):1591–1599. doi: 10.1016/0026-0495(76)90112-8. [DOI] [PubMed] [Google Scholar]
- Nordstrom J. L., Rodwell V. W., Mitschelen J. J. Interconversion of active and inactive forms of rat liver hydroxymethylglutaryl-CoA reductase. J Biol Chem. 1977 Dec 25;252(24):8924–8934. [PubMed] [Google Scholar]
- Popják G., Boehm G., Parker T. S., Edmond J., Edwards P. A., Fogelman A. M. Determination of mevalonate in blood plasma in man and rat. Mevalonate "tolerance" tests in man. J Lipid Res. 1979 Aug;20(6):716–728. [PubMed] [Google Scholar]
- Quintão E., Grundy S. M., Ahrens E. H., Jr Effects of dietary cholesterol on the regulation of total body cholesterol in man. J Lipid Res. 1971 Mar;12(2):233–247. [PubMed] [Google Scholar]
- Rogers D. H., Kim D. N., Lee K. T., Reiner J. M., Thomas W. A. Circadian variation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in swine liver and ileum. J Lipid Res. 1981 Jul;22(5):811–819. [PubMed] [Google Scholar]
- Samuel P., Crouse J. R., Ahrens E. H., Jr Evaluation of an isotope ratio method for measurement of cholesterol absorption in man. J Lipid Res. 1978 Jan;19(1):82–93. [PubMed] [Google Scholar]
- Schwartz C. C., Berman M., Vlahcevic Z. R., Halloran L. G., Gregory D. H., Swell L. Multicompartmental analysis of cholesterol metabolism in man. Characterization of the hepatic bile acid and biliary cholesterol precursor sites. J Clin Invest. 1978 Feb;61(2):408–423. doi: 10.1172/JCI108952. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shapiro D. J., Rodwell V. W. Fine structure of the cyclic rhythm of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Differential effects of cholesterol feeding and fasting. Biochemistry. 1972 Mar 14;11(6):1042–1045. doi: 10.1021/bi00756a014. [DOI] [PubMed] [Google Scholar]
- White E. C., McNamara D. J., Ahrens E. H., Jr Validation of a dietary record system for the estimation of daily cholesterol intake in individual outpatients. Am J Clin Nutr. 1981 Feb;34(2):199–203. doi: 10.1093/ajcn/34.2.199. [DOI] [PubMed] [Google Scholar]