当前位置： SCI文献检索 > ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS期刊下所有文献 > Control of hepatic fatty acid oxidation by 5'-AMP-activated protein kinase involves a malonyl-CoA-dependent and a malonyl-CoA-independent mechanism.

Control of hepatic fatty acid oxidation by 5'-AMP-activated protein kinase involves a malonyl-CoA-dependent and a malonyl-CoA-independent mechanism.

Abstract：

:Incubation of rat hepatocytes with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an activator of the 5'-AMP-activated protein kinase (AMPK), produced a twofold stimulation of palmitate oxidation and of the activity of carnitine palmitoyltransferase I (CPT-I), together with a profound decrease of the activity of acetyl-CoA carboxylase and of the intracellular level of malonyl-CoA. AICAR-induced CPT-I stimulation progressively blunted with time after cell permeabilization, pointing to reversal of conformational constraints of the enzyme in control cells due to the permeabilization-triggered dilution of intracellular malonyl-CoA. The stimulation stabilized at a steady 20-25%. This 20-25% increase in CPT-I activity survived upon complete removal of malonyl-CoA from the permeabilized cells, indicating that it was not dependent on the malonyl-CoA concentration of the cell. This malonyl-CoA-independent activation of CPT-I was not evident when mitochondria were isolated for assay of enzyme activity or when cells were disrupted by vigorous sonication. In addition, the microtubule stabilizer taxol prevented the malonyl-CoA-independent stimulation of CPT-I induced by AICAR. Hence, stimulation of hepatic fatty acid oxidation by AMPK seems to rely on the activation of CPT-I by two different mechanisms: deinhibition of CPT-I induced by depletion of intracellular malonyl-CoA levels and malonyl-CoA-independent stimulation of CPT-I, which might involve modulation of interactions between CPT-I and cytoskeletal components.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Velasco G,Geelen MJ,Guzmán M

doi

10.1006/abbi.1996.9784

subject

Has Abstract

pub_date

1997-01-15 00:00:00

pages

169-75

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(96)99784-2

journal_volume

337

pub_type

杂志文章

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