On the mechanism of the so-called uncoupling effect of medium- and short-chain fatty acids - PubMed (original) (raw)
On the mechanism of the so-called uncoupling effect of medium- and short-chain fatty acids
P Schönfeld et al. Biochim Biophys Acta. 1988.
Abstract
Octanoate applied to rat liver mitochondria respiring with glutamate plus malate or succinate (plus rotenone) under resting-state (State 4) conditions stimulates oxygen uptake and decreases the membrane potential, both effects being sensitive to oligomycin but not to carboxyatractyloside. Octanoate also decreases the rate of pyruvate carboxylation under the same conditions, this effect being correlated with the decrease of intramitochondrial content of ATP and increase of AMP. The decrease of pyruvate carboxylation and the change of mitochondrial adenine nucleotides are both reversed by 2-oxoglutarate. Fatty acids of shorter chain length have similar effects, though at higher concentrations. Addition of octanoate in the presence of fluoride (inhibitor of pyrophosphatase) produces intramitochondrial accumulation of pyrophosphate, even under conditions when oxidation of octanoate is prevented by rotenone. In isolated hepatocytes incubated with lactate plus pyruvate, octanoate also increases oxygen uptake and produces a shift in the profile of adenine nucleotides similar to that observed in isolated mitochondria. It decreases the 'efficiency' of gluconeogenesis, as expressed by the ratio between an increase of glucose production and an increase of oxygen uptake upon addition of gluconeogenic substrates (lactate plus pyruvate), and increases the reduction state of mitochondrial NAD. These effects taken together are not compatible with uncoupling, but point to intramitochondrial hydrolysis of octanoyl-CoA and probably also shorter chain-length acyl-CoAs. This mechanism probably functions as a 'safety valve' preventing a drastic decrease of intramitochondrial free CoA under a large supply of medium- and short-chain fatty acids.
Similar articles
- Octanoate affects 2,4-dinitrophenol uncoupling in intact isolated rat hepatocytes.
Sibille B, Keriel C, Fontaine E, Catelloni F, Rigoulet M, Leverve XM. Sibille B, et al. Eur J Biochem. 1995 Jul 15;231(2):498-502. doi: 10.1111/j.1432-1033.1995.tb20724.x. Eur J Biochem. 1995. PMID: 7635161 - Studies on the influence of fatty acids on pyruvate dehydrogenase interconversion in rat-liver mitochondria.
Walajtys-Rode EI. Walajtys-Rode EI. Eur J Biochem. 1976 Dec;71(1):229-37. doi: 10.1111/j.1432-1033.1976.tb11109.x. Eur J Biochem. 1976. PMID: 1009949 - Inhibition of citrulline synthesis by octanoate and its modulation by adenine nucleotides.
Lutz WH, Geisbuhler TP, Pollack JD, McClung HJ, Merola AJ. Lutz WH, et al. Biochem Med. 1985 Aug;34(1):1-10. doi: 10.1016/0006-2944(85)90055-9. Biochem Med. 1985. PMID: 4052056
Cited by
- Protective Role of Short-Chain Fatty Acids against Ang- II-Induced Mitochondrial Dysfunction in Brain Endothelial Cells: A Potential Role of Heme Oxygenase 2.
Kassan M, Kwon Y, Munkhsaikhan U, Sahyoun AM, Ishrat T, Galán M, Gonzalez AA, Abidi AH, Kassan A, Ait-Aissa K. Kassan M, et al. Antioxidants (Basel). 2023 Jan 10;12(1):160. doi: 10.3390/antiox12010160. Antioxidants (Basel). 2023. PMID: 36671022 Free PMC article. - Transcriptomic Responses Induced in Muscle and Adipose Tissues of Growing Pigs by Intravenous Infusion of Sodium Butyrate.
Zhang H, Ren E, Xu R, Su Y. Zhang H, et al. Biology (Basel). 2021 Jun 20;10(6):559. doi: 10.3390/biology10060559. Biology (Basel). 2021. PMID: 34203067 Free PMC article. - Muscle-Liver Substrate Fluxes in Exercising Humans and Potential Effects on Hepatic Metabolism.
Hu C, Hoene M, Plomgaard P, Hansen JS, Zhao X, Li J, Wang X, Clemmesen JO, Secher NH, Häring HU, Lehmann R, Xu G, Weigert C. Hu C, et al. J Clin Endocrinol Metab. 2020 Apr 1;105(4):1196-209. doi: 10.1210/clinem/dgz266. J Clin Endocrinol Metab. 2020. PMID: 31825515 Free PMC article. - Short- and medium-chain fatty acids in energy metabolism: the cellular perspective.
Schönfeld P, Wojtczak L. Schönfeld P, et al. J Lipid Res. 2016 Jun;57(6):943-54. doi: 10.1194/jlr.R067629. Epub 2016 Apr 14. J Lipid Res. 2016. PMID: 27080715 Free PMC article. Review. - Inhibition of β-oxidation is not a valid therapeutic tool for reducing oxidative stress in conditions of neurodegeneration.
Schönfeld P, Reiser G. Schönfeld P, et al. J Cereb Blood Flow Metab. 2017 Mar;37(3):848-854. doi: 10.1177/0271678X16642448. Epub 2016 Jul 20. J Cereb Blood Flow Metab. 2017. PMID: 27055779 Free PMC article.