Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1973 May;134(1):295–310. doi: 10.1042/bj1340295

An investigation into the role of malonyl-coenzyme A in isoprenoid biosynthesis

M J P Higgins 1, R G O Kekwick 1
PMCID: PMC1177809  PMID: 4579226

Abstract

1. [14C]Malonyl-CoA was incorporated into isoprenoids by cell-free yeast preparations, by preparations from pigeon and rat liver, and by Hevea brasiliensis latex. 2. In agreement with previous reports the incorporation of acetyl-CoA into isoprenoids was not inhibited by avidin and was not stimulated by HCO3. In a cell-free yeast preparation addition of HCO3 stimulated the formation of fatty acids from acetyl-CoA and decreased the incorporation into unsaponifiable lipids. 3. The labelling patterns of β-hydroxy-β-methylglutaryl-CoA formed from [2-14C]- and [1,3-14C]-malonyl-CoA in rat and pigeon liver preparations were those that would be expected if malonyl-CoA underwent decarboxylation to acetyl-CoA before incorporation. 4. The labelling pattern of ergosterol formed by cell-free yeast preparations from [2-14C]malonyl-CoA was also consistent with decarboxylation of malonyl-CoA before incorporation. 5. The incorporation of [2-14C]malonyl-CoA into mevalonate by rat liver preparations was related to the malonyl-CoA decarboxylase activity present in the preparation.

Full text

PDF
295

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABRAHAM S., MATTHES K. J., CHAIKOFF I. L. Effect of biotin and avidin on conversion of acetate to fatty acids and acetoacetate by preparations from rat liver and lactating rat mammary gland. Biochim Biophys Acta. 1961 Jan 1;46:197–198. doi: 10.1016/0006-3002(61)90667-9. [DOI] [PubMed] [Google Scholar]
  2. BACHHAWAT B. K., ROBINSON W. G., COON M. J. The enzymatic cleavage of beta-hydroxy-beta-methylglutaryl coenzyme A to acetoacetate and acetyl coenzyme A. J Biol Chem. 1955 Oct;216(2):727–736. [PubMed] [Google Scholar]
  3. BEINERT H., GREEN D. E., HELE P., HIFT H., VON KORFF R. W., RAMAKRISHNAN C. V. The acetate activating enzyme system of heart muscle. J Biol Chem. 1953 Jul;203(1):35–45. [PubMed] [Google Scholar]
  4. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  5. BLOOMFIELD D. K., BLOCH K. The formation of delta 9-unsaturated fatty acids. J Biol Chem. 1960 Feb;235:337–345. [PubMed] [Google Scholar]
  6. BRODIE J. D., WASSON G., PORTER J. W. ENZYME-BOUND INTERMEDIATES IN THE BIOSYNTHESIS OF MEVALONIC AND PALMITIC AICDS. J Biol Chem. 1964 May;239:1346–1356. [PubMed] [Google Scholar]
  7. BRODIE J. D., WASSON G., PORTER J. W. The participation of malonyl coenzyme A in the biosynthesis of mevalonic acid. J Biol Chem. 1963 Apr;238:1294–1301. [PubMed] [Google Scholar]
  8. BU'LOCK J. D., SMALLEY H. M., SMITH G. N. Malonate as a biosynthetic intermediate in Penicillium urticae. J Biol Chem. 1962 Jun;237:1778–1780. [PubMed] [Google Scholar]
  9. Chesterom C. J., Kekwick R. G. Formation of delta-3-isopentenyl monophosphate and pyrophosphate in the latex of Hevea brasiliensis. Arch Biochem Biophys. 1968 Apr;125(1):76–85. doi: 10.1016/0003-9861(68)90640-1. [DOI] [PubMed] [Google Scholar]
  10. DE DUVE C., PRESSMAN B. C., GIANETTO R., WATTIAUX R., APPELMANS F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J. 1955 Aug;60(4):604–617. doi: 10.1042/bj0600604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FLETCHER K., MYANT N. B. Biotin in the synthesis of fatty acid and cholesterol by mammalian liver. Nature. 1960 Nov 12;188:585–585. doi: 10.1038/188585a0. [DOI] [PubMed] [Google Scholar]
  12. FOSTER D. W., BLOOM B. A reciprocal relationship between fatty acid and cholesterol biosynthesis. Biochim Biophys Acta. 1963 Jun 18;70:341–343. doi: 10.1016/0006-3002(63)90759-5. [DOI] [PubMed] [Google Scholar]
  13. Fimognari G. M., Rodwell V. W. Mevalonate biosynthesis in rat liver. Lipids. 1970 Jan;5(1):104–108. doi: 10.1007/BF02531103. [DOI] [PubMed] [Google Scholar]
  14. GANGULY J. Studies on the mechanism of fatty acid synthesis. VII. Biosynthesis of fatty acids from malonyl CoA. Biochim Biophys Acta. 1960 May 6;40:110–118. doi: 10.1016/0006-3002(60)91320-2. [DOI] [PubMed] [Google Scholar]
  15. GREEN N. M. AVIDIN. 3. THE NATURE OF THE BIOTIN-BINDING SITE. Biochem J. 1963 Dec;89:599–609. doi: 10.1042/bj0890599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Galliard T., Michell R. H., Hawthorne J. N. Incorporation of phosphate into diphosphoinositide by subcellular fractions from liver. Biochim Biophys Acta. 1965 Dec 2;106(3):551–563. doi: 10.1016/0005-2760(65)90071-8. [DOI] [PubMed] [Google Scholar]
  17. Hsu R. Y., Wasson G., Porter J. W. The purification and properties of the fatty acid synthetase of pigeon liver. J Biol Chem. 1965 Oct;240(10):3736–3746. [PubMed] [Google Scholar]
  18. JAMES A. T. Qualitative and quantitative determination of the fatty acids by gas-liquid chromatography. Methods Biochem Anal. 1960;8:1–59. doi: 10.1002/9780470110249.ch1. [DOI] [PubMed] [Google Scholar]
  19. KLEIN H. P. Some observations on a cell free lipid synthesizing system from Saccharomyces cerevisiae. J Bacteriol. 1957 Apr;73(4):530–543. doi: 10.1128/jb.73.4.530-537.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. KNAUSS H. J., PORTER J. W., WASSON G. The biosynthesis of mevalonic acid from 1-C14-acetate by a rat liver enzyme system. J Biol Chem. 1959 Nov;234:2835–2840. [PubMed] [Google Scholar]
  21. LANGDON R. G., BLOCH K. The biosynthesis of squalene. J Biol Chem. 1953 Jan;200(1):129–134. [PubMed] [Google Scholar]
  22. LYNEN F., DECKER K. Das Coenzym A und seine biologischen Funktionen. Ergeb Physiol. 1957;49:327–424. [PubMed] [Google Scholar]
  23. LYNEN F., HENNING U., BUBLITZ C., SORBO B., KROPLIN-RUEFF L. Der chemische Mechanismus der Acetessigsäurebildung in der Leber. Biochem Z. 1958;330(4):269–295. [PubMed] [Google Scholar]
  24. MADSEN J., ABRAHAM S., CHAIKOFF I. L. THE CONVERSION OF GLUTAMATE CARBON TO FATTY ACID CARBON VIA CITRATE. I. THE INFLUENCE OF GLUCOSE IN LACTATING RAT MAMMARY GLAND SLICES. J Biol Chem. 1964 May;239:1305–1309. [PubMed] [Google Scholar]
  25. MELAMED M. D., GREEN N. M. AVIDIN. 2. PURIFICATION AND COMPOSITION. Biochem J. 1963 Dec;89:591–599. doi: 10.1042/bj0890591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. MERKENSCHLAGER M., SCHLOSSMANN K., KURZ W. Ein mechanischer Zellhomogenisator und seine Anwendbarkeit auf biologische Probleme. Biochem Z. 1957;329(4):332–340. [PubMed] [Google Scholar]
  27. ROWE C. E. THE OCCURRENCE AND METABOLISM IN VITRO OF UNESTERIFIED FATTY ACID IN MOUSE BRAIN. Biochim Biophys Acta. 1964 Aug 5;84:424–434. doi: 10.1016/0926-6542(64)90006-x. [DOI] [PubMed] [Google Scholar]
  28. RUDNEY H., FERGUSON J. J., Jr The biosynthesis of beta-hydroxy-beta-methylglutaryl coenzyme A in yeast. II. The formation of hydroxymethylglutaryl coenzyme A via the condensation of acetyl coenzyme A and acetoacetyl coenzyme A. J Biol Chem. 1959 May;234(5):1076–1080. [PubMed] [Google Scholar]
  29. RUDNEY H. The biosynthesis of beta-hydroxy-beta-methylglutaric acid. J Biol Chem. 1957 Jul;227(1):363–377. [PubMed] [Google Scholar]
  30. Rudney H., Stewart P. R., Majerus P. W., Vagelos P. R. The biosynthesis of beta-hydroxy-beta-methylglutaryl coenzyme A in yeast. V. The role of acyl carrier protein. J Biol Chem. 1966 Mar 10;241(5):1226–1228. [PubMed] [Google Scholar]
  31. STERN J. R. Optical properties of aceto-acetyl-S-coenzyme A and its metal chelates. J Biol Chem. 1956 Jul;221(1):33–44. [PubMed] [Google Scholar]
  32. Scholte H. R. The intracellular and intramitochondrial distribution of malonyl-CoA decarboxylase and propionyl-CoA carboxylase in rat liver. Biochim Biophys Acta. 1969 Mar 18;178(1):137–144. doi: 10.1016/0005-2744(69)90140-5. [DOI] [PubMed] [Google Scholar]
  33. Siperstein M. D., Fagan V. M. Feedback control of mevalonate synthesis by dietary cholesterol. J Biol Chem. 1966 Feb 10;241(3):602–609. [PubMed] [Google Scholar]
  34. Stewart P. R., Rudney H. The biosynthesis of beta-hydroxy-beta-methylglutaryl coenzyme A in yeast. 3. Purification and properties of the condensing enzyme thiolase system. J Biol Chem. 1966 Mar 10;241(5):1212–1221. [PubMed] [Google Scholar]
  35. White L. W., Rudney H. Regulation of 3-hydroxy-3-methylglutarate and mevalonate biosynthesis by rat liver homogenates. Effects of fasting, cholesterol feeding, and triton administration. Biochemistry. 1970 Jun 23;9(13):2725–2731. doi: 10.1021/bi00815a021. [DOI] [PubMed] [Google Scholar]
  36. Williamson I. P., Kekwick R. G. The formation of 5-phosphomevalonate by mevalonate kinase in Hevea brasiliensis latex. Biochem J. 1965 Sep;96(3):862–871. doi: 10.1042/bj0960862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yalpani M., Willecke K., Lynen F. Triacetic acid lactone, a derailment product of fatty acid biosynthesis. Eur J Biochem. 1969 Apr;8(4):495–502. doi: 10.1111/j.1432-1033.1969.tb00554.x. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES