Cholesterol pp 363-435

Part of the Subcellular Biochemistry book series (SCBI, volume 28) | Cite as

Cholesterol Metabolism and Tumor Cell Proliferation

  • Peter S. Coleman
  • Li-Chuan Chen
  • Laura Sepp-Lorenzino

Abstract

The functions assumed by free cholesterol in mammalian cells are diverse, ranging from that as a starting substrate for the synthesis of steroid hormones and bile salts to its less specifically understood but critical role as a principal lipid component of every cell membrane. Cholesterol biosynthesis begins with metabolically supplied cytoplasmic acetyl CoA that also serves as the common precursor for de novo fatty acid synthesis, and can be expressed by the reaction: 18 acetyl CoA + 1/2O2 + 10 H+ → cholesterol + 9 CO2 +18 CoA-SH. During the synthesis, the genesis of mevalonic acid (MVA) from 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), catalyzed by HMG-CoA reductase (HMGR), the third and principal rate-controlling enzyme of the pathway, leads to the production of diverse polyisoprenoid intermediates. Metabolism of MVA demonstrates considerable versatility through ensuing branching reactions that yield a host of terpene compounds used in the construction of an assortment of required metabolites [dolichol, ubiquinone(Coenzyme Q), isopentenyl adenine, heme a/a3], in addition to cholesterol itself. This chapter focuses on associations that link cholesterol and mitochondrial citrate export, as well as the metabolism of citrate-derived isoprenoid metabolites en route to cholesterol synthesis, with deregulated cell proliferation (i.e., cancer).

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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Peter S. Coleman
    • 1
  • Li-Chuan Chen
    • 2
  • Laura Sepp-Lorenzino
    • 3
  1. 1.Laboratory of Metabolic RegulationThe Boston Biomedical Research InstituteBostonUSA
  2. 2.Clinical Pharmacology BranchNational Cancer Institute, National Institutes of HealthBethesdaUSA
  3. 3.Program in Cell Biology and Genetics and Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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