13C-NMR spectroscopic evaluation of the citric acid cycle flux in conditions of high aspartate transaminase activity in glucose-perfused rat hearts

Biochimie ◽  
1998 ◽  
Vol 80 (12) ◽  
pp. 1013-1024 ◽  
Author(s):  
Son Tran-Dinh ◽  
Jacqueline A. Hoerter ◽  
Philippe Mateo ◽  
Franck Gyppaz ◽  
Martine Herve
Keyword(s):  
Citric Acid ◽  
13C Nmr ◽  
Citric Acid Cycle ◽  
Aspartate Transaminase ◽  
Transaminase Activity ◽  
Acid Cycle ◽  
Rat Hearts ◽  
Perfused Rat Hearts

scholarly journals Probing the Origin of Acetyl-CoA and Oxaloacetate Entering the Citric Acid Cycle from the13C Labeling of Citrate Released by Perfused Rat Hearts

1997 ◽  
Vol 272 (42) ◽  
pp. 26117-26124 ◽  
Author(s):  
Blandine Comte ◽  
Geneviève Vincent ◽  
Bertrand Bouchard ◽  
Christine Des Rosiers
Keyword(s):  
Citric Acid ◽  
Citric Acid Cycle ◽  
Acetyl Coa ◽  
Acid Cycle ◽  
Rat Hearts ◽  
Perfused Rat Hearts

Propionyl-L-carnitine-mediated improvement in contractile function of rat hearts oxidizing acetoacetate

1995 ◽  
Vol 268 (1) ◽  
pp. H441-H447 ◽  
Author(s):  
R. R. Russell ◽  
J. I. Mommessin ◽  
H. Taegtmeyer
Keyword(s):  
Citric Acid ◽  
Citric Acid Cycle ◽  
Mechanical Performance ◽  
Ketone Bodies ◽  
Contractile Function ◽  
Sustained Improvement ◽  
Acid Cycle ◽  
Rat Hearts ◽  
Beta Hydroxybutyrate ◽  
Contractile Failure

Prior evidence has suggested that propionyl-L-carnitine improves function in ischemic hearts by providing carnitine for dissipation of acyl-CoA derivatives and propionate for enrichment of the citric acid cycle. Because contractile failure in hearts oxidizing ketone bodies is due to sequestration of free coenzyme A, which can be reversed by the addition of anaplerotic substrates that enrich the citric acid cycle, experiments were performed to determine whether the addition of propionyl-L-carnitine (2 mM) can improve performance in working rat hearts utilizing acetoacetate (7.5 mM). Whereas the addition of propionyl-L-carnitine to acetoacetate resulted in a sustained improvement in the work output of the heart, the addition of propionate (2 mM) or L-carnitine (2 mM) alone to acetoacetate had negligible effects on contractile function. Propionyl-L-carnitine increased the uptake of acetoacetate by 130%, whereas beta-hydroxybutyrate release was minimal and unchanged compared with other groups. These observations show that rates of acetoacetate oxidation are increased commensurate with increased contractile function. Tissue metabolite data indicate that the utilization of propionyl-L-carnitine did not lead to accumulation of citric acid cycle intermediates in the span from citrate to 2-oxoglutarate but to an increase in the tissue content of malate. The results show that addition of propionyl-L-carnitine in hearts oxidizing acetoacetate results in improved mechanical performance that is comparable to the mechanical performance of hearts perfused with glucose as the only substrate. This improvement is most likely conferred by anaplerosis, as suggested by enhanced rates of acetoacetate utilization and citric acid flux.

scholarly journals Metabolism of [3-13C]pyruvate and [3-13C]propionate in normal and ischaemic rat heart in vivo: 1H- and 13C-NMR studies

1995 ◽  
Vol 312 (1) ◽  
pp. 75-81 ◽  
Author(s):  
B Sumegi ◽  
B Podanyi ◽  
P Forgo ◽  
K E Kover
Keyword(s):  
Citric Acid ◽  
13C Nmr ◽  
Rat Heart ◽  
Citric Acid Cycle ◽  
Nmr Studies ◽  
Acetyl Coa ◽  
1H And 13C Nmr ◽  
Acid Cycle ◽  
Propionyl Carnitine

The oxidation of [3-13C]pyruvate and [3-13C]propionate was studied in vivo in infused rats. The infused [3-13C]pyruvate was quickly converted to [3-13C]lactate in the blood, and the [3-13C]lactate formed was well metabolized in both normoxic and ischaemic hearts. Large differences (200-600%) in the 13C enrichment of alanine (C-3) and acetyl-CoA (C-2) compared with lactate (C-3) were found in both normoxic and ischaemic hearts, suggesting that the extracellular [3-13C]lactate preferentially entered a region of the cytoplasm which specifically transfers the labelled pyruvate (formed from [3-13C]lactate) to the mitochondria. The highly enriched mitochondrial pyruvate gave high enrichment in alanine and acetyl-CoA, which was detected by 1H- and 13C-NMR spectroscopy. Ischaemia increased 13C incorporation into the main cytoplasmic lactate pool and decreased 13C incorporation into citric acid cycle intermediates, mainly decreasing the pyruvate anaplerosis. Isoprenaline-induced ischaemia of the heart caused only a slight decrease in pyruvate oxidation. In contrast to the decreased anaplerosis of pyruvate, the anaplerosis of propionate (and propionyl-carnitine) increased significantly in ischaemic hearts, which may contribute to the protective effect of propionyl-carnitine seen in ischaemia. In addition, we found that [3-13C]propionate preferentially labelled aspartate C-3 in rat heart, suggesting incomplete randomization of label in the succinyl-CoA-malate span of the citric acid cycle. These data show that proton observed 13C edited spectroscopic methods, i.e. heteronuclear spin-echo and the one-dimensional heteronuclear multiple quantum coherence sequence, can be successfully used to study heart metabolism in vivo.

Use of a single 13C NMR resonance of glutamate for measuring oxygen consumption in tissue

1999 ◽  
Vol 277 (6) ◽  
pp. E1111-E1121 ◽  
Author(s):  
F. Mark H. Jeffrey ◽  
Alexander Reshetov ◽  
Charles J. Storey ◽  
Rui A. Carvalho ◽  
A. Dean Sherry ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Oxygen Consumption ◽  
Citric Acid ◽  
Magnetic Resonance ◽  
Citric Acid Cycle ◽  
Single Measurement ◽  
Acid Cycle ◽  
Nmr Data ◽  
Rat Hearts ◽  
C Nmr

A kinetic model of the citric acid cycle for calculating oxygen consumption from13C nuclear magnetic resonance (NMR) multiplet data has been developed. Measured oxygen consumption (MV˙o 2) was compared with MV˙o 2 predicted by the model with 13C NMR data obtained from rat hearts perfused with glucose and either [2-13C]acetate or [3-13C]pyruvate. The accuracy of MV˙o 2 measured from three subsets of NMR data was compared: glutamate C-4 and C-3 resonance areas; the doublet C4D34 (expressed as a fraction of C-4 area); and C-4 and C-3 areas plus several multiplets of C-2, C-3, and C-4. MV˙o 2 determined by set 2(C4D34 only) gave the same degree of accuracy as set 3(complete data); both were superior to set 1(C-4 and C-3 areas). Analysis of the latter suffers from the correlation between citric acid cycle flux and exchange between α-ketoglutarate and glutamate, resulting in greater error in estimating MV˙o 2. Analysis of C4D34 is less influenced by correlation between parameters, and this single measurement provides the best opportunity for a noninvasive measurement of oxygen consumption.

scholarly journals Glutamate–oxaloacetate transaminase activity promotes palmitate lipotoxicity in rat hepatocytes by enhancing anaplerosis and citric acid cycle flux

2018 ◽  
Vol 294 (9) ◽  
pp. 3081-3090 ◽  
Author(s):  
Robert A. Egnatchik ◽  
Alexandra K. Leamy ◽  
Sarah A. Sacco ◽  
Yi Ern Cheah ◽  
Masakazu Shiota ◽  
...  
Keyword(s):  
Citric Acid ◽  
Citric Acid Cycle ◽  
Rat Hepatocytes ◽  
Transaminase Activity ◽  
Glutamate Oxaloacetate Transaminase ◽  
Acid Cycle
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