scholarly journals Elimination and replenishment of tricarboxylic acid-cycle intermediates in myocardium

1981 ◽  
Vol 194 (3) ◽  
pp. 867-875 ◽  
Author(s):  
E M Nuutinen ◽  
K J Peuhkurinen ◽  
E P Pietiläinen ◽  
J K Hiltunen ◽  
I E Hassinen

1. The contribution of Co2 fixation to the anaplerotic mechanisms in the myocardium was investigated in isolated perfused rat hearts. 2. K+-induced arrest of the heart was used to elicit a transition in the concentrations of the intermediates of the tricarboxylic acid cycle. 3. Incorporation of 14C from [14]bicarbonate into tricarboxylic acid-cycle intermediates was measured and the rates of the reactions of the cycle were estimated by means of a linear optimization program which solves the differential equations describing a simulation model of the tricarboxylic acid cycle and related reactions. 4. The results showed that the rate of CO2 fixation is dependent on the metabolic state of the myocardium. Upon a sudden diminution of cellular ATP consumption, the pool size of the tricarboxylic acid-cycle metabolites increased and the rate of label incorporation from [14C]bicarbonate into the cycle metabolites increased simultaneously. The computer model was necessary to separate the rapid equilibration between bicarbonate and some metabolites from the potentially anaplerotic reactions. The main route of anaplerosis during metabolite accumulation was through malate + oxaloacetate. Under steady-state conditions there was a constant net outward flow from the tricarboxylic acid cycle via the malate + oxaloacetate pool, with a concomitant anaplerotic flow from metabolites forming succinyl-CoA (3-carboxypropionyl-CoA).

1978 ◽  
Vol 170 (2) ◽  
pp. 241-247 ◽  
Author(s):  
J K Hiltunen

The metabolic effects of the hypoglycaemic agent pent-4-enoate were studied in isolated, beating or potassium-arrested rat hearts. The addition of 0.8mM-pent-4-enoate to the perfusion fluid increased O2 consumption by 76% in the arrested heart and by 14% in the beating heart; the concentration ratio of phosphocreatine/creatine increase concomitantly by 47% and 27% respectively. Perfusion of the heart with pent-4-enoate resulted in a 30-fold increase in the concentration of the pool of tricarboxylic acid-cycle intermediates in the tissue, about 90% of this increase being due to malate. The sum of the concentrations of the myocardial free amino acids remained virtually unchanged during the accumulation of the tricarboxylic acid-cycle intermediates. It was concluded that pent-4-enoate can be effectively metabolized in the myocardium and that its metabolism probably proceeds via propionyl-CoA, since pent-4-enoate reproduces many of the metabolic characteristics of propionate in the cardiac muscle. The accumulation of the tricarboxylic acid-cycle intermediates is probably due to carboxylation of propionyl-CoA. The response pattern of the metabolite concentrations in the cardiac muscle is quite different from that in the liver, in which decrease of the concentrations of the tricarboxylic acid-cycle intermediates has been observed previously [Williamson, Rostand & Peterson (1970) J. Biol. Chem. 245, 3242-3251].


1969 ◽  
Vol 15 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Victor F. Lachica ◽  
Paul A. Hartman

The stimulatory effect of acetyl-CoA and the inhibitory effect by L-aspartate and some intermediates of the tricarboxylic acid cycle in the assimilation of CO2 by crude extracts of group D streptococci suggest that the pyruvate carboxylase of Streptococcus faecium and the phosphoenolpyruvate carboxylase of S. bovis are allosteric enzymes. This implies that these enzymes are sites for the control of the amount of aspartate and of the tricarboxylic acid cycle intermediates synthesized.


1982 ◽  
Vol 208 (3) ◽  
pp. 577-581 ◽  
Author(s):  
K J Peuhkurinen ◽  
E M Nuutinen ◽  
E P Pietiläinen ◽  
J K Hiltunen ◽  
I E Hassinen

The increase in the metabolite pool size of the tricarboxylic acid cycle in the isolated perfused rat heart after a decrease in the ATP consumption by KCl-induced arrest was used to study the anaplerotic mechanisms. During net anaplerosis the label incorporation into the tricarboxylic acid-cycle intermediates from [1-14C]pyruvate increased and occurred mainly by pathways not involving prior release of the label to CO2. A method for determination of the specific radioactivity of mitochondrial pyruvate was devised, and the results corroborated the notion that tissue alanine can be used as an indicator of the specific radioactivity of intracellular pyruvate.


2013 ◽  
Vol 129 (1) ◽  
pp. 107-119 ◽  
Author(s):  
Mussie G. Hadera ◽  
Olav B. Smeland ◽  
Tanya S. McDonald ◽  
Kah Ni Tan ◽  
Ursula Sonnewald ◽  
...  

1967 ◽  
Vol 105 (1) ◽  
pp. 333-341 ◽  
Author(s):  
Kirsti Lampiaho ◽  
E. Kulonen

1. The metabolism of incubated slices of sponge-induced granulation tissue, harvested 4–90 days after the implantation, was studied with special reference to the capacity of collagen synthesis and to the energy metabolism. Data are also given on the nucleic acid contents during the observation period. Three metabolic phases were evident. 2. The viability of the slices for the synthesis of collagen was studied in various conditions. Freezing and homogenization destroyed the capacity of the tissue to incorporate proline into collagen. 3. Consumption of oxygen reached the maximum at 30–40 days. There was evidence that the pentose phosphate cycle was important, especially during the phases of the proliferation and the involution. The formation of lactic acid was maximal at about 20 days. 4. The capacity to incorporate proline into collagen hydroxyproline in vitro was limited to a relatively short period at 10–30 days. 5. The synthesis of collagen was dependent on the supply of oxygen and glucose, which latter could be replaced in the incubation medium by other monosaccharides but not by the metabolites of glucose or tricarboxylic acid-cycle intermediates.


2021 ◽  
Author(s):  
Dung Hoang Anh Mai ◽  
Thu Thi Nguyen ◽  
Eun Yeol Lee

The ethylmalonyl-CoA pathway is one of three known anaplerotic pathways that replenish tricarboxylic acid cycle intermediates and plays a major role in the carbon metabolism of many alpha-proteobacteria including Methylosinus...


1996 ◽  
Vol 271 (4) ◽  
pp. E788-E799 ◽  
Author(s):  
F. M. Jeffrey ◽  
C. J. Storey ◽  
A. D. Sherry ◽  
C. R. Malloy

A previous model using 13C nuclear magnetic resonance isotopomer analysis provided for direct measurement of the oxidation of 13C-enriched substrates in the tricarboxylic acid cycle and/or their entry via anaplerotic pathways. This model did not allow for recycling of labeled metabolites from tricarboxylic acid cycle intermediates into the acetyl-CoA pool. An extension of this model is now presented that incorporates carbon flow from oxaloacetate or malate to acetyl-CoA. This model was examined using propionate metabolism in the heart, in which previous observations indicated that all of the propionate consumed was oxidized to CO2 and water. Application of the new isotopomer model shows that 2 mM [3-13C]propionate entered the tricarboxylic acid cycle as succinyl-CoA (an anaplerotic pathway) at a rate equal to 52% of tricarboxylic acid cycle turnover and that all of this carbon entered the acetyl-CoA pool and was oxidized. This was verified using standard biochemical analysis; from the rate (mumol.min-1.g dry wt-1) of propionate uptake (4.0 +/- 0.7), the estimated oxygen consumption (24.8 +/- 5) matched that experimentally determined (24.4 +/- 3).


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