scholarly journals Multiple Mass Isotopomer Tracing of Acetyl-CoA Metabolism in Langendorff-perfused Rat Hearts

2015 ◽  
Vol 290 (13) ◽  
pp. 8121-8132 ◽  
Author(s):  
Qingling Li ◽  
Shuang Deng ◽  
Rafael A. Ibarra ◽  
Vernon E. Anderson ◽  
Henri Brunengraber ◽  
...  
1997 ◽  
Vol 272 (42) ◽  
pp. 26117-26124 ◽  
Author(s):  
Blandine Comte ◽  
Geneviève Vincent ◽  
Bertrand Bouchard ◽  
Christine Des Rosiers

2004 ◽  
Vol 279 (19) ◽  
pp. 19574-19579 ◽  
Author(s):  
Aneta E. Reszko ◽  
Takhar Kasumov ◽  
France David ◽  
Kathryn A. Jobbins ◽  
Katherine R. Thomas ◽  
...  

Little is known about the sources of acetyl-CoA used for the synthesis of malonyl-CoA, a key regulator of mitochondrial fatty acid oxidation in the heart. In perfused rat hearts, we previously showed that malonyl-CoA is labeled from both carbohydrates and fatty acids. This study was aimed at assessing the mechanisms of incorporation of fatty acid carbons into malonyl-CoA. Rat hearts were perfused with glucose, lactate, pyruvate, and a fatty acid (palmitate, oleate or docosanoate). In each experiment, substrates were13C-labeled to yield singly or/and doubly labeled acetyl-CoA. The mass isotopomer distribution of malonyl-CoA was compared with that of the acetyl moiety of citrate, which reflects mitochondrial acetyl-CoA. In the presence of labeled glucose or lactate/pyruvate, the13C labeling of malonyl-CoA was up to 2-fold lower than that of mitochondrial acetyl-CoA. However, in the presence of a fatty acid labeled in its first acetyl moiety, the13C labeling of malonyl-CoA was up to 10-fold higher than that of mitochondrial acetyl-CoA. The labeling of malonyl-CoA and of the acetyl moiety of citrate is compatible with peroxisomal β-oxidation forming C12and C14acyl-CoAs and contributing >50% of the fatty acid-derived acetyl groups that end up in malonyl-CoA. This fraction increases with the fatty acid chain length. By supplying acetyl-CoA for malonyl-CoA synthesis, peroxisomal β-oxidation may participate in the control of mitochondrial fatty acid oxidation in the heart. In addition, this pathway may supply some acyl groups used in protein acylation, which is increasingly recognized as an important regulatory mechanism for many biochemical processes.


2002 ◽  
Vol 283 (4) ◽  
pp. H1379-H1386 ◽  
Author(s):  
Myriame Poirier ◽  
Geneviève Vincent ◽  
Aneta E. Reszko ◽  
Bertrand Bouchard ◽  
Joanne K. Kelleher ◽  
...  

Little is known about the sources of cytosolic acetyl-CoA used for the synthesis of malonyl-CoA, a key regulator of fatty acid oxidation in the heart. We tested the hypothesis that citrate provides acetyl-CoA for malonyl-CoA synthesis after its mitochondrial efflux and cleavage by cytosolic ATP-citrate lyase. We expanded on a previous study where we characterized citrate release from perfused rat hearts (Vincent G, Comte B, Poirier M, and Des Rosiers C. Citrate release by perfused rat hearts: a window on mitochondrial cataplerosis. Am J Physiol Endocrinol Metab 278: E846–E856, 2000). In the present study, we show that citrate release rates, ranging from 6 to 22 nmol/min, can support a net increase in malonyl-CoA concentrations induced by changes in substrate supply, at most 0.7 nmol/min. In experiments with [U-13C](lactate + pyruvate) and [1-13C]oleate, we show that the acetyl moiety of malonyl-CoA is derived from both pyruvate and long-chain fatty acids. This 13C-labeling of malonyl-CoA occurred without any changes in its concentration. Hydroxycitrate, an inhibitor of ATP-citrate lyase, prevents increases in malonyl-CoA concentrations and decreases its labeling from [U-13C](lactate + pyruvate). Our data support at least a partial role of citrate in the transfer from the mitochondria to cytosol of acetyl units for malonyl-CoA synthesis. In addition, they provide a dynamic picture of malonyl-CoA metabolism: even when the malonyl-CoA concentration remains constant, there appears to be a constant need to supply acetyl-CoA from various carbon sources, both carbohydrates and lipids, for malonyl-CoA synthesis.


1997 ◽  
Vol 272 (42) ◽  
pp. 26125-26131 ◽  
Author(s):  
Blandine Comte ◽  
Geneviève Vincent ◽  
Bertrand Bouchard ◽  
Manon Jetté ◽  
Sylvie Cordeau ◽  
...  

1986 ◽  
Vol 334 (2) ◽  
pp. 145-148 ◽  
Author(s):  
Kazumi Sono ◽  
Yoshinobu Akimoto ◽  
Kazuyoshi Kurahashi ◽  
Motohatsu Fujiwara

1999 ◽  
Vol 58 (9) ◽  
pp. 1497-1500 ◽  
Author(s):  
Ken Kageyama ◽  
Takeshi Murakami ◽  
Kenji Iizuka ◽  
Kumi Sato ◽  
Kazuo Ichihara ◽  
...  

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