Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat
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The requirement for carnitine and the malonyl-CoA sensitivity of carnitine palmitoyl-transferase I (EC 2.3.1.21) were measured in isolated mitochondria from eight tissues of animal or human origin using fixed concentrations of palmitoyl-CoA (50 microM) and albumin (147 microM). The Km for carnitine spanned a 20-fold range, rising from about 35 microM in adult rat and human foetal liver to 700 microM in dog heart. Intermediate values of increasing magnitude were found for rat heart, guinea pig liver and skeletal muscle of rat, dog and man. Conversely, the concentration of malonyl-CoA required for 50% suppression of enzyme activity fell from the region of 2-3 microM in human and rat liver to only 20 nM in tissues displaying the highest Km for carnitine. Thus, the requirement for carnitine and sensitivity to malonyl-CoA appeared to be inversely related. The Km of carnitine palmitoyltransferase I for palmitoyl-CoA was similar in tissues showing large differences in requirement for carnitine. Other experiments established that, in addition to liver, heart and skeletal muscle of fed rats contain significant quantities of malonyl-CoA and that in all three tissues the level falls with starvation. Although its intracellular location in heart and skeletal muscle is not known, the possibility is raised that malonyl-CoA (or a related compound) could, under certain circumstances, interact with carnitine palmitoyltransferase I in non-hepatic tissues and thereby exert control over long chain fatty acid oxidation.
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Malonyl-CoA is an intermediate in the de novo synthesis of FA and is an allosteric inhibitor of CPT-1, thereby inhibiting fat oxidation.
“Malonyl-CoA is an intermediate in the de novo synthesis of FA and is an allosteric inhibitor of CPT-1, thereby inhibiting fat oxidation [158].”
From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [158]
The Results report that malonyl-CoA inhibits CPT I, and the Discussion links this inhibition to control of fatty acid oxidation and synthesis. The copy does not explicitly identify malonyl-CoA as a de novo fatty-acid-synthesis intermediate or describe its inhibition of CPT I as allosteric. (LLM, conf=0.85)
Experimental — accuracy not yet measuredβ-oxidation was presumably stimulated, in part, due to decreases in citrate and the downstream lipogenic intermediate malonyl-CoA, which inhibits CPT1.
“Here β-oxidation was presumably stimulated, in part, due to decreases in citrate and the downstream lipogenic intermediate malonyl-CoA, which inhibits CPT1 (McGarry et al., 1983).”
From Regulation of Substrate Utilization by the Mitochondrial Pyruvate Carrier (2014) · cites this paper as McGarry et al., 1983
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- Authors
- McGarry, J. D., Mills, S. E., Long, C. S., & Foster, D. W.
- Affiliations
- University of Texas Health Science Center at Dallas (US)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1983-07-15
- Volume
- 214
- Issue
- 1
- Pages
- 21-28
- ISSN
- 0264-6021 (ISSN-L)
- PMC
- PMC1152205
- OpenAlex
- W1577348758
- Cited by
- 556
- References
- 15
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 11 · 2021: 16 · 2020: 6 · 2019: 12 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 10 · 2014: 14 · 2013: 16 · 2012: 12
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service
- 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
- carnitine palmitoyltransferase 1, malonyl-CoA inhibition, palmitoyl-CoA, long-chain fatty acid oxidation, starvation, heart, skeletal muscle, liver
- MeSH terms
- Acyl Coenzyme A, Acyltransferases, Animals, Carnitine, Carnitine O-Palmitoyltransferase, Dogs, Female, Guinea Pigs, Humans, Kinetics, Liver, Male, Malonyl Coenzyme A, Mitochondria, Muscles, Myocardium, Palmitoyl Coenzyme A, Rats, Inbred Strains, Starvation, Rats, In Vitro Techniques
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