Citrate and the Conversion of Carbohydrate into Fat
Open accessAbstract
A cell-free system, consisting of particle-free cytoplasm and mitochondria prepared from rat liver, has been used to study the transfer of acetyl groups from the intramitochondrial to the extramitochondrial space during fatty acid synthesis. 14C-Pyruvate, generated from 14C-alanine, was used to generate intramitochondrial 14C-acetyl-CoA. Fatty acid synthesis was followed by measuring the incorporation of 3H2O and 14C. Pool dilution experiments showed that the acetyl group of intramitochondrial acetyl-CoA leaves the mitochondria in the form of citrate, or of a closely related tricarboxylate. (-)-Hydroxycitrate, an inhibitor of citrate cleavage enzyme, strongly inhibits fatty acid synthesis from 14C-alanine. On the other hand, (-)-hydroxycitrate has little or no effect on respiration, phosphorylation, and citrate accumulation during the course of the experiments. n-Butylmalonate, an inhibitor of malate permease, also inhibits fatty acid synthesis. This inhibition is reversed by malate. n-Butylmalonate probably exerts its effect by preventing the activation of α-ketoglutarate and tricarboxylate permeases by malate. It is concluded that citrate is the major carrier in the transfer of acetyl groups from the mitochondrial matrix to the cytoplasm.
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Cleavage of cytosolic citrate by ACL provides a route for delivering acetyl-CoA into the cytosol and supporting fatty acid synthesis.
“Given that the mitochondrial membrane is impermeable to acetyl-CoA, it was appreciated early on that cleavage of cytosolic citrate by ACL provides a route for delivering acetyl-CoA into the cytosol and, thus, supporting fatty acid synthesis (117).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [117]
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Carnitine—metabolism and functions
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“Given that the mitochondrial membrane is impermeable to acetylCoA, it was appreciated early on that cleavage of cytosolic citrate by ACL provides a route for delivering acetyl-CoA into the cytosol and, thus, supporting fatty acid synthesis (117).”
BackgroundCompartmentalised acyl-CoA metabolism and roles in chromatin regulation
Trefely, S., Lovell, C. D., Snyder, N. W., & Wellen, K. E. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.005 · Cited by 272 · see citing works
- Authors
- Watson, J. A., & Lowenstein, J. M.
- Affiliations
- University of California, San Francisco (US)
- ORCID
- Watson, John A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1970-11
- Volume
- 245
- Issue
- 22
- Pages
- 5993-6002
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1566163765
- Cited by
- 262
- References
- 19
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 10 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 2
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- citrate, fatty acid synthesis, acetyl-CoA, mitochondrial matrix, tricarboxylate carrier, hydroxycitrate, liver mitochondria, pyruvate
- MeSH terms
- Alanine, Animals, Carbon Isotopes, Cell-Free System, Citrates, Coenzyme A, Cytoplasm, Fatty Acids, Ketoglutaric Acids, Malates, Malonates, Mitochondria, Liver, Tritium, Membrane Transport Proteins, Membrane Transport Modulators, Rats
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