Yeast squalene synthase. A mechanism for addition of substrates and activation by NADPH

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Publication Type Journal Article
School or College College of Science
Department Chemistry
Creator Poulter, Charles Dale
Other Author Mookhtiar, K. A.; Kalinowski, S.S.; Zhang, D.
Title Yeast squalene synthase. A mechanism for addition of substrates and activation by NADPH
Date 1993-04-15
Description Squalene synthase catalyzes the condensation of two molecules of farnesyl diphosphate (FPP) to give presqualene diphosphate (PSPP) and the subsequent reductive rearrangement of PSPP to squalene. Previous studies of the mechanism of addition of FPP to the enzyme have led to conflicting interpretations of initial velocity measurements (Beytia, E., Qureshi, A. A., and Porter, J.W. (1973) J. Biol. Chem. 248, 1856-1867; Agnew, W.S., and Popjak, G. (1978) J. Biol. Chem. 253, 4566-4573). Initial velocities for synthesis of PSPP and squalene were measured over a wider range of FPP and NADPH concentrations than previously reported, using a soluble form of recombinant enzyme. In the absence of NADPH, PSPP formation was activated by FPP at concentrations above approximately 0.5 microM. At fixed levels of NADPH, the dependence of initial rates of PSPP and squalene synthesis on FPP concentrations indicated that the C15 substrate added by a sequential mechanism. In addition, NADPH stimulated synthesis of PSPP by 40-fold at saturating levels of the cofactor. This stimulation is, at least in part, by reduction of PSPP to squalene.
Type Text
Publisher American Society for Biochemistry and Molecular Biology (ASBMB)
Volume 269
Issue 15
First Page 11201
Last Page 11207
Subject Enzyme Activation; Sesquiterpenes; Kinetics
Subject MESH NADP; Saccharomyces cerevisiae
Language eng
Bibliographic Citation Poulter, C. D. (1993). Yeast squalene synthase. Journal of Biological Chemistry 269(15), 11201-7.
Rights Management (c)American Society for Biochemistry and Molecular Biology (ASBMB)
Format Medium application/pdf
Identifier ir-main,12088
ARK ark:/87278/s6dz0snx
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 704589
Reference URL
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