Effect of acetate and octanoate on tricarboxylic acid cycle metabolite disposal during propionate oxidation in the perfused rat heart

1984 ◽  
Vol 801 (3) ◽  
pp. 429-436 ◽  
Author(s):  
Kaj E. Sundqvist ◽  
Keijo J. Peuhkurinen ◽  
J. Kalervo Hiltunen ◽  
Ilmo E. Hassinen
Keyword(s):  
Rat Heart ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Perfused Rat Heart ◽  
Propionate Oxidation

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.

Computer simulation of metabolism in pyruvate-perfused rat heart. II. Krebs cycle

1979 ◽  
Vol 237 (3) ◽  
pp. R159-R166 ◽  
Author(s):  
M. C. Kohn ◽  
M. J. Achs ◽  
D. Garfinkel
Keyword(s):  
Redox Potential ◽  
Rat Heart ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Krebs Cycle ◽  
Coordinated Control ◽  
Work Load ◽  
Metabolic Model ◽  
Tricarboxylic Acid ◽  
Perfused Rat Heart

A realistic metabolic model of the tricarboxylic acid cycle in the perfused rat heart was constructed to help explain the sequence of biochemical events regulating the metabolism of exogenous pyruvate following a large increase in work load. The unchelated Mg2+ level was the most important controlling factor. The resulting mixture of chelated and unchelated nucleotides and tribasic acids effected coordinated control of citrate synthase, aconitase, isocitrate dehydrogenase, succinyl CoA synthetase, fumarase, and nucleoside diphosphokinase, because Mg2+-chelates are generally substrates whereas unchelated species are inhibitors. Succinate dehydrogenase is largely controlled by the ubiquinone redox potential. The fluxes through alpha-ketoglutarate and malate dehydrogenases are largely dependent on thepyridine nucleotide redox potential, but the succinyl CoA-to-CoASH ratio strongly affects the former enzyme as well. The model predicts an accumulation of succinate during the transition to higher work output.

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 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.

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