Flux control exerted by mitochondrial outer membrane carnitine palmitoyltransferase over β-oxidation, ketogenesis and tricarboxylic acid cycle activity in hepatocytes isolated from rats in different metabolic states
Open accessAbstract
The Flux Control Coefficients of mitochondrial outer membrane carnitine palmitoyltransferase (CPT I) with respect to the overall rates of β-oxidation, ketogenesis and tricarboxylic acid cycle activity were measured in hepatocytes isolated from rats in different metabolic states (fed, 24 h-starved, starved–refed and starved/insulin-treated). These conditions were chosen because there is controversy as to whether, when significant control ceases to be exerted by CPT I over the rate of fatty oxidation [Moir and Zammit (1994) Trends Biochem. Sci. 19, 313–317], this is transferred to one or more steps proximal to acylcarnitine synthesis (e.g. decreased delivery of fatty acids to the liver) or to the reaction catalysed by mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase [Hegardt (1995) Biochem. Soc. Trans. 23, 486–490]. Therefore isolated hepatocytes were used in the present study to exclude the involvement of changes in the rate of delivery of non-esterified fatty acids (NEFA) to the liver, such as occur in vivo, and to ascertain whether, under conditions of constant supply of NEFA, CPT I retains control over the relevant fluxes of fatty acid oxidation to ketones and carbon dioxide, or whether control is transferred to another (intrahepatocytic) site. The results clearly show that the Flux Control Coefficients of CPT I with respect to overall β-oxidation and ketogenesis are very high under all conditions investigated, indicating that control is not lost to another intrahepatic site during the metabolic transitions studied. The control of CPT I over tricarboxylic acid cycle activity was always very low. The significance of these findings for the integration of fatty acid and carbohydrate metabolism in the liver is discussed.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Potential mechanisms to explain the beneficial effects of targeting mitochondrial fatty acid oxidation could be the concomitant enhancement of hepatic ketone bodies, CO2, acid soluble products, ATP production, and endergonic processes (e.g., gluconeogenesis) seen in previous publications.
“Potential mechanisms to explain the beneficial effects of targeting mitochondrial FAO could be the concomitant enhancement of hepatic ketone bodies, CO2, acid soluble products, ATP production, and endergonic processes (*e.g.,* gluconeogenesis) seen in previous publications ([38](#B38), [130](#B130), [158](#B158)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Chapter 4 Preparation of Isolated Rat Liver Cells
Seglen, P. O. (1976) · Methods in cell biology · doi:10.1016/s0091-679x(08)61797-5 · Cited by 5,297 · see citing works
A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis.
McGarry, J. D., Mannaerts, G. P., & Foster, D. W. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108764 · Cited by 736 · see citing works
Mowbray, J. (1983) · Biochemical Society Transactions · doi:10.1042/bst0110325 · Cited by 316 · see citing works
The glucose paradox. Is glucose a substrate for liver metabolism?
Katz, J. J., & McGarry, J. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111610 · Cited by 278 · see citing works
Kiorpes, T. C., Hoerr, D. C., Ho, W., et al. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42763-3 · Cited by 152 · see citing works
Differential inhibition of ketogenesis by malonyl-CoA in mitochondria from fed and starved rats
Cook, G. A., Otto, D. A., & Cornell, N. W. (1980) · Biochemical Journal · doi:10.1042/bj1920955 · Cited by 116 · see citing works
Cook, G. A. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)71315-3 · Cited by 115 · see citing works
Grantham, B. D., & Zammit, V. A. (1988) · Biochemical Journal · doi:10.1042/bj2490409 · Cited by 87 · see citing works
Self-citationOntko, J. A., & Johns, M. L. (1980) · Biochemical Journal · doi:10.1042/bj1920959 · Cited by 78 · see citing works
Casals, N., Roca, N., Guerrero, M., Gil‐Gómez, G., Ayté, J., Ciudad, C. J., & Hegardt, F. G. (1992) · Biochemical Journal · doi:10.1042/bj2830261 · Cited by 77 · see citing works
Grantham, B. D., & Zammit, V. A. (1986) · Biochemical Journal · doi:10.1042/bj2390485 · Cited by 71 · see citing works
Self-citationKolodziej, M. P., Crilly, P. J., Corstorphine, C. G., et al. (1992) · Biochemical Journal · doi:10.1042/bj2820415 · Cited by 70 · see citing works
Serra, D., Casals, N., Asins, G., Royo, T., Ciudad, C. J., & Hegardt, F. G. (1993) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1993.1557 · Cited by 53 · see citing works
Lopes‐Cardozo, M., Mulder, I., van Vugt, F., Hermans, P. G. C., van den Bergh, S. G., Klazinga, W., & Vries-Akkerman, E. A. D. (1975) · Molecular and Cellular Biochemistry · doi:10.1007/bf01751311 · Cited by 53 · see citing works
Garland, P. B., Shepherd, D., Nicholls, D. G., & Ontko, J. A. (1968) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(68)90005-8 · Cited by 51 · see citing works
Mc, S., Di, W., Tn, P., et al. (1983) · PubMed · Cited by 51 · see citing works
Nonhomogeneous labeling of liver mitochondrial acetyl-CoA
Rosiers, C. D., David, F., Garneau, M., & Brunengraber, H. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)52332-2 · Cited by 50 · see citing works
Moir, A. M. B., & Zammit, V. A. (1993) · Biochemical Journal · doi:10.1042/bj2890049 · Cited by 47 · see citing works
Self-citationLilly, K., Bugaisky, G. E., Umeda, P. K., & BIEBER, L. L. (1990) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(90)90532-4 · Cited by 47 · see citing works
Guzmán, M., & Geelen, M. J. H. (1992) · Biochemical Journal · doi:10.1042/bj2870487 · Cited by 44 · see citing works
Chatterjee, B., Song, C. S., Kim, J., et al. (1988) · Biochemistry · doi:10.1021/bi00425a018 · Cited by 41 · see citing works
Boon, M. R., & Zammit, V. A. (1988) · Biochemical Journal · doi:10.1042/bj2490645 · Cited by 40 · see citing works
Self-citationGuzmán, M., Kolodziej, M. P., Caldwell, A. M., Corstorphine, C. G., & Zammit, V. A. (1994) · Biochemical Journal · doi:10.1042/bj3000693 · Cited by 35 · see citing works
Self-citationMonitoring the partitioning of hepatic fatty acids in vivo: keeping track of control
Zammit, V. A., & Moir, A. M. B. (1994) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(94)90068-x · Cited by 31 · see citing works
Self-citationSMALL, J. R. (1993) · Biochemical Journal · doi:10.1042/bj2960423 · Cited by 25 · see citing works
Quant, P. A. (1990) · Biochemical Society Transactions · doi:10.1042/bst0180994 · Cited by 18 · see citing works
Self-citationMicrosomal carnitine acyltransferases
BROADWAY, N. M., & SAGGERSON, E. D. (1995) · Biochemical Society Transactions · doi:10.1042/bst0230490 · Cited by 15 · see citing works
Moir, A. M. B., & Zammit, V. A. (1994) · Biochemical Journal · doi:10.1042/bj3040177 · Cited by 12 · see citing works
Self-citationHegardt, F. G. (1995) · Biochemical Society Transactions · doi:10.1042/bst0230486 · Cited by 10 · see citing works
Zammit, V. A. (1995) · Biochemical Journal · doi:10.1042/bj3120057 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- Drynan, L., Quant, P. A. and Zammit, V. A. (1996) Biochem. J., in the press 8
- Hegardt, F. G. (1995) Biochem. Soc. Trans. 23, 486-490
- Quant, P. A. (1990) Biochem. Soc. Trans. 18, 994-995
- Broadway, N. M. and Saggerson, E. D. (1995) Biochem. Soc. Trans. 23, 490-494
Cited by
Sorted by citations
Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504 · see citing works
A general introduction to the biochemistry of mitochondrial fatty acid β‐oxidation
Houten, S. M., & Wanders, R. J. A. (2010) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-010-9061-2 · Cited by 1,020 · see citing works
Schooneman, M. G., Vaz, F. M., Houten, S. M., & Soeters, M. R. (2013) · Diabetes · doi:10.2337/db12-0466 · Cited by 616 · see citing works
Toxicity of statins on rat skeletal muscle mitochondria
Kaufmann, P., Török, M., Zahno, A., Waldhauser, K. M., Brecht, K., & Krähenbühl, S. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6235-z · Cited by 263 · see citing works
Mitochondrial fatty acid oxidation in obesity
Serra, D., Mera, P., Malandrino, M. I., Mir, J. F., & Herrero, L. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4875 · Cited by 246 · see citing works
Skeletal muscle insulin resistance: roles of fatty acid metabolism and exercise
Turcotte, L. P., & Fisher, J. S. (2008) · Physical Therapy · doi:10.2522/ptj.20080018 · Cited by 209 · see citing works
Orellana-Gavaldà, J. M., Herrero, L., Malandrino, M. I., Pañeda, A., Sol Rodríguez-Peña, M., Petry, H., Asins, G., Van Deventer, S., Hegardt, F. G., & Serra, D. (2011) · Hepatology · doi:10.1002/hep.24140 · Cited by 135 · see citing works
Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake
Olson, D. P., Pulinilkunnil, T., Cline, G. W., Shulman, G. I., & Lowell, B. B. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913492107 · Cited by 109 · see citing works
- Authors
- DRYNAN, L., QUANT, P. A., & ZAMMIT, V. A.
- Affiliations
- Hannah Research Foundation (GB)
- University of Cambridge (GB)
- Corresponding author
- DRYNAN, Lesley
- ORCID
- ZAMMIT, Victor A.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1996-08-01
- Volume
- 317
- Issue
- 3
- Pages
- 791-795
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1217554
- OpenAlex
- W2237575183
- Cited by
- 107
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- carnitine palmitoyltransferase 1, flux control coefficients, fatty acid beta-oxidation, ketogenesis, TCA cycle, fatty acid oxidation, hepatocytes, fasting, refeeding, insulin, HMG-CoA synthase, free fatty acids
- MeSH terms
- Animals, Carnitine O-Palmitoyltransferase, Citric Acid Cycle, Female, Food, Insulin, Intracellular Membranes, Ketone Bodies, Mitochondria, Liver, Oxidation-Reduction, Starvation, Rats, Wistar, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
