scholarly journals Anaerobic rat heart. Effects of glucose and tricarboxylic acid-cycle metabolites on metabolism and physiological performance

1970 ◽  
Vol 118 (2) ◽  
pp. 221-227 ◽  
Author(s):  
D. G. Penney ◽  
J. Cascarano
Keyword(s):  
Energy Expenditure ◽  
Rat Heart ◽  
Cell Function ◽  
Tricarboxylic Acid Cycle ◽  
Systolic Pressure ◽  
Lactate Production ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Physiological Performance ◽  
Production Ratio

1. The ability of tricarboxylic acid-cycle metabolites to influence the physiological performance of the perfused anaerobic rat heart was investigated. Energy expenditure/h [(beats/min)×60×systolic pressure/g of protein] for various anoxic conditions compared with oxygenated control hearts were: 5mm-glucose, 4.5%; 20mm- or 40mm-glucose, 10%; 20mm-glucose plus fumerate+malate+glutamate, 29%; 20mm-glucose plus oxaloacetate and α-oxoglutarate, 31%. 2. The energy expenditure/lactate production ratio was increased by the tricarboxylic acid-cycle metabolites, indicating that alterations in anaerobic physiological performance did not result from changes in glycolysis. 3. Analysis of tissue constituents provided further indication of an enhanced energy status for fumarate+malate+glutamate- and oxaloacetate+α-oxoglutarate-perfused hearts; tissue concentrations of both glycogen and ATP were higher than in the 20mm-glucose-perfused groups. 4. A marked increase in the accumulation of succinate in tissues perfused with oxaloacetate+α-oxoglutarate or fumarate+malate+glutamate provided further evidence that these metabolites were stimulating mitochondrial energy production under anoxia. 5. These studies indicate that mitochondrial ATP production can be stimulated in an isolated mammalian tissue perfused under anaerobiosis with a resulting enhancement of cell function.

Computer simulation of energy metabolism in acidotic cardiac ischemia

1982 ◽  
Vol 242 (5) ◽  
pp. R533-R544 ◽  
Author(s):  
M. J. Achs ◽  
D. Garfinkel
Keyword(s):  
Rat Heart ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Low Ph ◽  
Cardiac Ischemia ◽  
Acid Cycle ◽  
Glucose Depletion ◽  
Experimental Preparation ◽  
Glycolytic Rate ◽  
Fatty Acid Mobilization

Construction and fit to experimental data of a computer model of glycolysis, the tricarboxylic acid cycle, and related metabolism in the perfused rat heart involving 63 enzyme submodels is described. The experimental preparation simulated is a rat heart perfused with Krebs bicarbonate solution containing glucose and insulin whose pH was lowered to 6.6 by equilibration with 35% CO2-65% O2. The glycolytic rate falls sharply and ischemia results, becoming apparent after 3.5 min. The model initially ascribes the fall in glycolysis largely to inhibition of hexokinase by accumulated glucose 6-phosphate and inactivation of phosphofructokinase by the low pH and subsequently to cytoplasmic glucose depletion owing to limitation of glucose uptake by the external acidosis. At the same time there is insufficiently deep hypoxia to trigger substantial mobilization of endogenous fuels (e.g., glycogenolysis or fatty acid mobilization, so that these hearts become ischemic primarily owing to a shortage of metabolic fuel.

scholarly journals Role of NADP+-linked malic enzymes as regulators of the pool size of tricarboxylic acid-cycle intermediates in the perfused rat heart

1987 ◽  
Vol 243 (3) ◽  
pp. 853-857 ◽  
Author(s):  
K E Sundqvist ◽  
J Heikkilä ◽  
I E Hassinen ◽  
J K Hiltunen
Keyword(s):  
Malic Enzyme ◽  
Rat Heart ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Mass Action ◽  
Acid Cycle ◽  
Perfused Rat Heart ◽  
Order Of Magnitude ◽  
Propionate Oxidation ◽  
Tricarboxylic Acid Cycle Intermediates

Cytosolic and mitochondrial concentrations of malate, 2-oxoglutarate, isocitrate and pyruvate in the isolated perfused rat heart were measured by non-aqueous tissue fractionation, taking the NADP-linked isocitrate dehydrogenase as indicator reactions for the free [NADPH]/[NADP+] ratios. The mass-action ratios of NADP-linked malic enzymes (EC 1.1.1.40) were found to be on the side of pyruvate carboxylation by more than one order of magnitude in both the cytosolic and the mitochondrial spaces in hearts perfused with glucose, whereas during propionate perfusion this ratio approached the equilibrium constant (Keq.) of malic enzyme. The results consequently indicate that the NADP-linked malic enzymes cannot be responsible for the feed-out (cataplerotic) reactions from the tricarboxylic acid cycle which occur during glucose perfusion. Only when other anaplerotic fluxes into the cycle are high, as during propionate oxidation, which results in accumulation of tricarboxylic acid-cycle intermediates, is a steady state reached which allows efflux via the malic enzyme.

scholarly journals Tricarboxylic acid cycle flux and enzyme activities in the isolated working rat heart

1981 ◽  
Vol 200 (3) ◽  
pp. 701-703 ◽  
Author(s):  
G J Cooney ◽  
H Taegtmeyer ◽  
E A Newsholme
Keyword(s):  
Oxygen Consumption ◽  
Enzyme Activities ◽  
Rat Heart ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Work Load ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Oxoglutarate Dehydrogenase ◽  
Working Rat Heart

Flux through the tricarboxylic acid cycle was calculated from oxygen consumption in hearts perfused near the physiological work load. Activities of citrate synthase, 2-oxoglutarate dehydrogenase and succinate dehydrogenase were measured in the same hearts. Only the activities of 2-oxoglutarate dehydrogenase correlated with calculated fluxes through the cycle.

scholarly journals Metabolism of pent-4-enoate in rat heart. Reduction of the double bond

1981 ◽  
Vol 194 (2) ◽  
pp. 427-432 ◽  
Author(s):  
J K Hiltunen ◽  
E J Davis
Keyword(s):  
Double Bond ◽  
Rat Heart ◽  
No Reduction ◽  
Tricarboxylic Acid Cycle ◽  
Liver Mitochondria ◽  
Tricarboxylic Acid ◽  
Beta Oxidation ◽  
Initial Oxidation ◽  
Acid Cycle ◽  
Tricarboxylic Acid Cycle Intermediates

1. Soluble extracts from rat heart and liver mitochondria were used to evaluate the early steps in the conversion of pent-4-enoyl-CoA into tricarboxylic acid-cycle intermediates. Hitherto the unresolved problem was the reduction of the double bond of pent-4-enoate. 2. Soluble extracts from heart mitochondria reduced pent-4-enoyl-CoA and penta-2,4-dienoyl-CoA in the presence of NADPH at rates (nmol/min per mg of protein) of 0.9 +/- 0.1 and 132 +/- 8 and from the liver mitochondria at the rates of 1.9 +/- 0.2 and 52 +/- 6 respectively. No reduction of acryloyl-CoA was found. 3. We show that primarily the double bond in position 4, not in position 2, of penta-2,4-dienoyl-CoA is reduced. 4. It is concluded that the principal metabolic pathway of penta-4-enoate is reduction of the double bond in position 4 after an initial oxidation of penta-2,4-dienoyl-CoA. The pent-2-enoyl-CoA thus formed can be further metabolized by the usual enzymes of beta-oxidation, and by the further metabolism of propionyl-CoA to tricarboxylic acid-cycle intermediates.

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