Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation

Awan, MM; Saggerson, E D

doi:10.1042/bj2950061

Cited by 188 publications

(122 citation statements)

References 64 publications

(51 reference statements)

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“…However, it is possible that other malonyl-CoAutilizing enzymes may be involved in terminating the malonylCoA signal to the cell in non-lipogenic tissues. Such a role has been suggested for the fatty acid chain-elongation system [17] and for malonyl-CoA decarboxylase [4,18]. However, malonylCoA decarboxylase is not thought to have a cytosolic distribution in mammalian tissues [19].…”

Section: Introductionmentioning

confidence: 99%

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

Zammit

1999

Biochemical Journal

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Long-chain acyl-CoA esters have potent specific actions (e.g. on gene transcription, membrane trafficking) as well as non-specific ones (e.g. on phospholipid bilayers). They are synthesized on the cytosolic aspects of several intracellular membranes, to give rise to (a) cytosolic pool(s) to which a variety of enzymes and processes have access, including some localized in the nucleus. Their concentration in cells is highly regulated, interconversion with corresponding acylcarnitines being the most important mechanism involved. This reaction is catalysed by cytosol-accessible carnitine long-chain acyl (palmitoyl) transferase activities that are themselves located on multiple membrane systems. Regulation of these activities is through the inhibitory action of malonyl-CoA. Hence the existence of a potent malonyl-CoA-acyl-CoA axis through which many processes involved in the maintenance of mammalian cell function are regulated. The molecular, topographical and physiological interactions that make this possible are described and discussed.

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Section: Introductionmentioning

confidence: 99%

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

Zammit

1999

Biochemical Journal

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“…Insulin is also able to regulate fatty acid metabolism in the myocyte. For example, in skeletal muscle, insulin can inhibit fatty acid oxidation through the inhibition of carnitine palmitoyltransferase I, an effect that is mediated through increased intracellular levels of malonyl-CoA (4,14). It has now also been shown that insulin increases fatty acid esterification into triacylglycerols in skeletal muscle while simultaneously reducing fatty acid oxidation (13,22).…”

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confidence: 99%

Insulin induces the translocation of the fatty acid transporter FAT/CD36 to the plasma membrane

Luiken

Dyck

Han³

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

189

173

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-It is well known that muscle contraction and insulin can independently translocate GLUT-4 from an intracellular depot to the plasma membrane. Recently, we have shown that the fatty acid transporter FAT/CD36 is translocated from an intracellular depot to the plasma membrane by muscle contraction (Ͻ30 min) (Bonen et al. J Biol Chem 275: 14501-14508, 2000). In the present study, we examined whether insulin also induced the translocation of FAT/CD36 in rat skeletal muscle. In studies in perfused rat hindlimb muscles, we observed that insulin increased fatty acid uptake by ϩ51%. Insulin increased the rate of palmitate incorporation into triacylglycerols, diacylglycerols, and phospholipids (P Ͻ 0.05) while reducing muscle palmitate oxidation (P Ͻ 0.05). Perfusing rat hindlimb muscles with insulin increased plasma membrane FAT/CD36 by ϩ48% (P Ͻ 0.05), whereas concomitantly the intracellular FAT/CD36 depot was reduced by 68% (P Ͻ 0.05). These insulin-induced effects on FAT/CD36 translocation were inhibited by the phosphatidylinositol 3-kinase inhibitor LY-294002. Thus these studies have shown for the first time that insulin can induce the translocation of FAT/CD36 from an intracellular depot to the plasma membrane.This reveals a previously unknown level of regulation of fatty acid transport by insulin and may well have important consequences in furthering our understanding of the relation between fatty acid metabolism and insulin resistance.

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“…E-boxes are binding sites for ubiquitously expressed bHLH family pro- 82-2-312-5041; E-mail: kyungsup59@yumc.yonsei.ac.kr. 1 The abbreviations used are: ACC, acetyl-CoA carboxylase; MRF, muscle regulatory factor; bHLH, basic helix-loop-helix; 5Ј-UTR, 5Ј-untranslated region; EMSA, electrophoretic mobility shift assay; PCR, polymerase chain reaction; kb, kilobase pair(s); bp, base pair(s); PCR, polymerase chain reaction; RT-PCR, reverse transcriptase-polymerase chain reaction; PIPES, 1,4-piperazinediethanesulfonic acid.…”

mentioning

confidence: 99%

“…Malonyl-CoA serves as the active donor of two carbon atoms in fatty acid synthesis and strongly inhibits fatty acid ␤-oxidation by acting as a potent inhibitor of carnitine palmitoyltransferase I (1,2). Carnitine palmitoyltransferase I resides on the surface of the mitochondrial membrane and generates palmitoylcarnitine from palmitoyl-CoA.…”

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confidence: 99%

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Cloning of Human Acetyl-CoA Carboxylase β Promoter and Its Regulation by Muscle Regulatory Factors

Lee

Moon

et al. 2001

Journal of Biological Chemistry

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The 280-kDa ␤-isoform of acetyl-CoA carboxylase (ACC␤) is predominantly expressed in heart and skeletal muscle, whereas the 265-kDa ␣-isoform (ACC␣) is the major ACC in lipogenic tissues. The ACC␤ promoter showed myoblast-specific promoter activity and was strongly induced by MyoD in NIH3T3 cells. Serial deletions of the promoter revealed that MyoD acts on the E-boxes located at positions ؊498 to ؊403 and on the proximal region including the 5-untranslated region. Destruction of the E-boxes at positions ؊498 to ؊403 by site-directed mutagenesis resulted in a significant decrease of MyoD responsiveness. The "TGAAA" at ؊32 to ؊28 and the region around the transcription start site play important roles in basal transcription, probably as a TATA box and an Inr element, respectively. Mutations of another E-box at ؊14 to ؊9 and a "GCCTGTCA" sequence at ؉17 to ؉24 drastically decreased the MyoD responsiveness. The novel cis-element GCCTGTCA was preferentially bound by MyoD homodimer in EMSA and conferred MyoD responsiveness to a luciferase reporter, which was repressed by the overexpression of E12. This finding is unique since activation via E-boxes is mediated by heterodimers of MyoD and E-proteins. We screened a human skeletal muscle cDNA library to isolate clones expressing proteins that bind to the region around the GCCTGTCA (؉8 to ؉27) sequence, and isolated Myf4 and Myf6 cDNAs. Electrophoretic mobility shift assay showed that recombinant Myf4 and Myf6 bind to this novel cis-element. Moreover, transient expression of Myf6 induced significant activation on the ACC␤ promoter or an artificial promoter harboring this novel cis-element. These findings suggest that muscle regulatory factors, such as MyoD, Myf4, and Myf6, contribute to the muscle-specific expression of ACC␤ via E-boxes and the novel cis-element GCCTGTCA.

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Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation

Cited by 188 publications

References 64 publications

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

Insulin induces the translocation of the fatty acid transporter FAT/CD36 to the plasma membrane

Cloning of Human Acetyl-CoA Carboxylase β Promoter and Its Regulation by Muscle Regulatory Factors

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