Malonyl-CoA inhibition of peroxisomal carnitine octanoyltransferase
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Although the malonyl-CoA sensitivity of peroxisomal carnitine octanoyltransferase (COT) is reportedly lost on solubilization, we show that malonyl-CoA does inhibit the purified enzyme. Assay conditions such as buffer composition, pH, acyl-CoA substrate and the presence or absence of BSA can affect the observed inhibition. When assayed in the absence of BSA, COT shows simple competitive inhibition by malonyl-CoA. The Ki value for inhibition of purified COT is high (106 microM) compared with physiological concentrations (1-6 microM) and other short-chain acyl-CoA esters inhibit COT to the same degree. However, when COT is assayed in intact peroxisomes, the Ki for malonyl-CoA is almost 20-fold lower than found with the purified enzyme, whereas inhibition by other short-chain acyl-CoA esters does not change significantly. Several features of the inhibition of peroxisomal COT, including the specificity of malonyl-CoA over other short-chain acyl-CoA esters, resemble those of carnitine palmitoyltransferase (CPT)-I, suggesting that the regulation of COT and CPT-I in parallel may be necessary for the control of cellular fatty acid metabolism.
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The dominant allosteric inhibitor malonyl-CoA regulates CROT similarly to CPT1A.
“Interestingly, the dominant allosteric inhibitor malonyl-CoA regulates CROT similarly to CPT1A (28,52).”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [52]
In the 'Kinetics of COT assayed in peroxisomes' section, the paper says malonyl-CoA inhibits peroxisomal COT more selectively than other short-chain acyl-CoA esters and that features of this inhibition resemble CPT-I. It does not establish that the inhibition is allosteric: a separate regulatory binding site is proposed as a possibility, while inhibition of purified COT is described as competitive. Page numbers were not supplied with these passages. (LLM, conf=0.86)
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Regulation of hepatic fatty acid oxidation and ketone body production
McGarry, J. D., & Foster, D. W. (1980) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.49.070180.002143 · Cited by 1,460 · see citing works
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Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation*
Gerin, I., Clerbaux, L.-A., Haumont, O., Lanthier, N., Das, A. K., Burant, C. F., Leclercq, I. A., MacDougald, O. A., & Bommer, G. T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152090 · Cited by 382 · see citing works
- Authors
- A'Bháird, N. N., & Ramsay, R. R.
- Affiliations
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, and Molecular Biology Division, Veterans Administration Medical Center, 4150 Clement Street, San Francisco, CA 94121, U.S.A.
- San Francisco VA Medical Center (US)
- ORCID
- Ramsay, R R
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1992-09-01
- Volume
- 286
- Issue
- 2
- Pages
- 637-640
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1132947
- OpenAlex
- W2336110607
- Cited by
- 30
- References
- 1
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- malonyl-CoA, carnitine octanoyltransferase, peroxisomes, enzyme inhibition, competitive inhibition, carnitine palmitoyltransferase 1, substrate specificity
- MeSH terms
- Animals, Carnitine Acyltransferases, Cattle, Hydrogen-Ion Concentration, Kinetics, Liver, Malonyl Coenzyme A, Microbodies, Substrate Specificity
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