Evaluation of the affinity and turnover number of both hepatic mitochondrial and microsomal carnitine acyltransferases: Relevance to intracellular partitioning of acyl-CoAs

K.A.H. Abo-Hashema; M.H. Cake; M.A. Lukas; J. Knudsen

doi:10.1021/bi9912185

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Evaluation of the affinity and turnover number of both hepatic mitochondrial and microsomal carnitine acyltransferases: Relevance to intracellular partitioning of acyl-CoAs

Journal article

Peer reviewed

Evaluation of the affinity and turnover number of both hepatic mitochondrial and microsomal carnitine acyltransferases: Relevance to intracellular partitioning of acyl-CoAs

K.A.H. Abo-Hashema, M.H. Cake, M.A. Lukas and J. Knudsen

Biochemistry, Vol.38(48), pp.15840-15847

1999

DOI: https://doi.org/10.1021/bi9912185

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Abstract

Mitochondrial carnitine palmitoyltransferase I (CPT I) and microsomal carnitine acyltransferase I (CAT I) regulate the entry of fatty acyl moieties into their respective organelles. Thus, CPT I and CAT I occupy prominent positions in the pathways responsible for energy generation in mitochondria and the assembly of VLDL in the endoplasmic reticulum, respectively. Previous attempts to determine the intrinsic kinetic properties of CPT I and CAT I have been hampered by the occurrence of sigmoidal velocity curves. This was overcome, in this study, by the inclusion of recombinant acyl-CoA binding protein in the assay medium. For the first time, we have determined the concentrations of total functional enzyme (E(t)) by specific radiolabeling of the active site, the dissociation constants (K(d)) and the turnover numbers of CPT I and CAT I toward the CoA esters of oleic acid (C18:1) and docosahexaenoic acid (C22:6). The data show that carnitine inhibits CAT I at physiological concentrations which are not inhibitory to CPT I. Thus, carnitine concentration is likely to be a significant factor in determining the partitioning of acyl-CoAs between mitochondria and microsomes, a role which has not been previously recognized. Moreover, the finding that CAT I elicits a lower turnover toward the CoA ester of C22:6 (25 s-1) than toward that of C18:1 (111 s-1), while having similar K(d) values, suggests the use of this polyunsaturated fatty acid to inhibit VLDL biosynthesis.

Details

Title: Evaluation of the affinity and turnover number of both hepatic mitochondrial and microsomal carnitine acyltransferases: Relevance to intracellular partitioning of acyl-CoAs
Authors/Creators: K.A.H. Abo-Hashema (Author/Creator) - Murdoch University
M.H. Cake (Author/Creator) - Murdoch University
M.A. Lukas (Author/Creator) - Murdoch University
J. Knudsen (Author/Creator) - Murdoch University
Publication Details: Biochemistry, Vol.38(48), pp.15840-15847
Publisher: ACS Publications
Identifiers: 991005541648607891
Murdoch Affiliation: School of Biological Sciences and Biotechnology; School of Mathematical and Physical Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.197 Molecular & Cell Biology - Mitochondria; 1.197.1196 Inborn Metabolic Errors
Web Of Science research areas: Biochemistry & Molecular Biology
ESI research areas: Biology & Biochemistry