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Cited by 564

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

High Rates of Fatty Acid Oxidation during Reperfusion of Ischemic Hearts Are Associated with a Decrease in Malonyl-CoA Levels Due to an Increase in 5’-AMP-activated Protein Kinase Inhibition of Acetyl-CoA Carboxylase

Open access
Kudo, Naomi, Barr, Amy J., Barr, Rick L., Desai, Snehal, Lopaschuk, Gary D.·1995·Journal of Biological Chemistry
DOI 10.1074/jbc.270.29.17513
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Abstract

We determined whether high fatty acid oxidation rates during aerobic reperfusion of ischemic hearts could be explained by a decrease in malonyl-CoA levels, which would relieve inhibition of carnitine palmitoyl-transferase 1, the rate-limiting enzyme involved in mitochondrial uptake of fatty acids. Isolated working rat hearts perfused with 1.2 mM palmitate were subjected to 30 min of global ischemia, followed by 60 min of aerobic reperfusion. Fatty acid oxidation rates during reperfusion were 136% higher than rates seen in aerobically perfused control hearts, despite the fact that cardiac work recovered to only 16% of pre-ischemic values. Neither the activity of carnitine palmitoyltransferase 1, or the IC50 value of malonyl-CoA for carnitine palmitoyl-transferase 1 were altered in mitochondria isolated from aerobic, ischemic, or reperfused ischemic hearts. Levels of malonyl-CoA were extremely low at the end of reperfusion compared to levels seen in aerobic controls, as was the activity of acetyl-CoA carboxylase, the enzyme which produces malonyl-CoA. The activity of 5'-AMP-activated protein kinase, which has been shown to phosphorylate and inactivate acetyl-CoA carboxylase in other tissues, was significantly increased at the end of ischemia, and remained elevated throughout reperfusion. These results suggest that accumulation of 5'-AMP during ischemia results in an activation of AMP-activated protein kinase, which phosphorylates and inactivates ACC during reperfusion. The subsequent decrease in malonyl-CoA levels wil result in accelerated fatty acid oxidation rates during reperfusion of ischemic hearts.

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Metadata

Authors
Kudo, N., Barr, A. J., Barr, R. L., Desai, S., & Lopaschuk, G. D.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1995-07
Volume
270
Issue
29
Pages
17513-17520
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.270.29.17513
OpenAlex
W2039167216
Cited by
564
References
1
FWCI
11.68
Type
journal article
Language
en
Open access
hybrid

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