The effect of fasting on the activity of liver carnitine palmitoyltransferase and its inhibition by malonyl-CoA

Bremer, Jon

doi:10.1016/0005-2760(81)90282-4

Cited by 245 publications

(123 citation statements)

References 14 publications

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“…The CPT1 assay was performed as described by Bremer (30). Briefly, 200 g of mitochondrial protein was added to the assay medium containing 20 mM Hepes (pH 7.3), 75 mM KCl, 2 mM KCN, 1% fat-free BSA, 70 M palmitoyl-CoA, 0.25 mM L-[ 3 H]carnitine, with or without 10, 30, 50, or 100 M malonyl-CoA.…”

Section: Preparation Of Mitochondria and Measurement Of Mitochondrialmentioning

confidence: 99%

Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver

Dobrzyń

Miyazaki

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

358

301

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Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the biosynthesis of monounsaturated fatty acids. Mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased energy expenditure, and up-regulated expression of several genes encoding enzymes of fatty acid ␤-oxidation in liver. The mechanisms by which SCD deficiency leads to these metabolic changes are presently unknown. Here we show that the phosphorylation and activity of AMP-activated protein kinase (AMPK), a metabolic sensor that regulates lipid metabolism during increased energy expenditure is significantly increased (Ϸ40%, P < 0.01) in liver of SCD1 knockout mice (SCD1؊͞؊). In parallel with the activation of AMPK, the phosphorylation of acetyl-CoA carboxylase at Ser-79 was increased and enzymatic activity was decreased (Ϸ35%, P < 0.001), resulting in decreased intracellular levels of malonyl-CoA (Ϸ47%, P < 0.001). An SCD1 mutation also increased AMPK phosphorylation and activity and increased acetyl-CoA carboxylase phosphorylation in leptin-deficient ob͞ob mice. Lower malonyl-CoA concentrations are known to derepress carnitine palmitoyltransferase 1 (CPT1). In SCD1؊͞؊ mice, CPT1 and CPT2 activities were significantly increased (in both cases Ϸ60%, P < 0.001) thereby stimulating the oxidation of mitochondrial palmitoyl-CoA. Our results identify AMPK as a mediator of increased fatty acid oxidation in liver of SCD1-deficient mice.

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Section: Preparation Of Mitochondria and Measurement Of Mitochondrialmentioning

confidence: 99%

Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver

Dobrzyń

Miyazaki

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

358

301

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“…CPT activity was measured by following the timecourse and extent of formation of [3H]-acylcarnitine from [3H]-carnitine (26). The assay medium contained 60 mM KC1 , 40 mM mannitol, 20 mM Hepes, 0.15 mM EGTA, 1.5 mM KCN, defatted bovine serum albumin (0.5%), 42 gM palmitoyl CoA, 0.35 mM L-carnitine (0.6 Ci [3H]-methylcarnitine) and 25 or 50 gl of the isolated mitochondrial fraction (approximately 0.03 mg of protein per assay).…”

Section: Measurement Of Carnitine Palmitoyltransferase I and Ii Maximmentioning

confidence: 99%

Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: Effect of indomethacin treatment

Seelaender¹,

Curi²,

Colquhoun³

et al. 1998

IUBMB Life

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Summary. The syndrome of cancer cachexia is accompanied by several alterations of lipid metabolism, especially that in the liver. In this study we have investigated a possible mechanism whereby the presence of the Walker 256 carcinosarcoma affects hepatic fatty acid oxidative capacity in tumour-bearing rats. Hepatic mitochondrial outer membrane carnitine palmitoyltransferase I (CPT I), generally accepted as the main site of regulation of fatty acid oxidation, was unaffected by the presence of the extra-hepatic tumour. However, mitochondrial inner-membrane carnitine palmitoyltransferase II (CPT II) activity was markedly decreased in mitochondria isolated from the liver of tumour-bearing rats. Immuno-detection by Western blotting using a CPT IIspecific antibody identified two bands (corresponding to Mr 69,000 and 54,000) in tumourbearing rats whereas only the normal-sized CPT II was present (at the expected Mr 69,000) in mitochondria from control rats. It is suggested that the emergence of the second, smaller protein may represent a catalytically less active protein that arises in vivo, since its appearance was not affected by the inclusion of proteolysis inhibitors in the mitochondrial preparation buffers. Treatment of the tumour-bearing rats with indomethacin, a prostaglandin (including PGE2) synthesis inhibitor, increased CPT II activity to levels even higher than those found in the control animals. It is suggested that PGE2 may play a role in the control of CPT II expression in the liver of tumour-bearing rats. Indomethacin treatment did not affect either of the two CPT activities of the mitochondria isolated from tumour tissue.

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“…Consequently, the rate of fatty acid oxidation would be expected to be inhibited at the CPT I reaction simply through the effects of insulin on ACC activity. However, acylcarnitine synthesis has the potential to be much more sensitive to the effects of insulin, because hypoinsulinaemic or insulin-resistant states result in a desensitization of CPT I to malonyl-CoA [48][49][50][51][52][53]. Consequently, the effects of changes in the absolute concentration of malonyl-CoA in the liver are amplified by the adaptation of CPT I kinetic properties during conditions characterized by absolute or relative insulin deficiency [38,54,54a].…”

Section: Enzymes Involved In the Partitioning Of Fatty Acids Between mentioning

confidence: 99%

Role of insulin in hepatic fatty acid partitioning: emerging concepts

Zammit

1996

Biochemical Journal

114

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The effect of fasting on the activity of liver carnitine palmitoyltransferase and its inhibition by malonyl-CoA

Cited by 245 publications

References 14 publications

Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver

Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver

Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: Effect of indomethacin treatment

Role of insulin in hepatic fatty acid partitioning: emerging concepts

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