Effects of Myocardial Ischemia and Long Chain Acyl CoA on Mitochondrial Adenine Nucleotide Translocator

1984 ◽  
pp. 185-202 ◽  
Author(s):  
D. J. Paulson ◽  
A. L. Shug
Keyword(s):  
Myocardial Ischemia ◽  
Adenine Nucleotide ◽  
Adenine Nucleotide Translocator ◽  
Chain Acyl ◽  
Long Chain

Acyl-CoA inhibition of adenine nucleotide translocation in ischemic myocardium

1975 ◽  
Vol 228 (3) ◽  
pp. 689-692 ◽  
Author(s):  
AL Shug ◽  
E Shrago ◽  
N Bittar ◽  
JD Folts ◽  
Koke
Keyword(s):  
Myocardial Ischemia ◽  
Tissue Concentration ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Energy Charge ◽  
Heart Tissue ◽  
Acid Oxidation ◽  
Inner Mitochondrial Membrane ◽  
Chain Acyl ◽  
Long Chain

The translocation of adenine nucleotides across the inner mitochondrial membrane and the tissue concentration of long-chain acyl-CoA esters were studied in dog heart after experimental myocardial ischemia. Ligation of the anterior coronary artery initiated events leading to an early decrease in adenine nucleotide translocase activity. A reciprocal increase in the concentration of heart tissue long-chain acyl-CoA esters was also observed. Adjacent nonischemic tissue showed changes intermediate between that of ischemic and normal heart tissue. It is postulated that a decrease in fatty acid oxidation after myocardial ischemia would lead to an accumulation of long-chain acyl-CoA esters, which in turn would inhibit adenine nucleotide translocation. The net result would be a lowering of the energy charge of the cell, adversely affecting muscle contraction and electrical conduction.

scholarly journals Effect of long-chain fatty acyl-CoA on mitochondrial and cytosolic ATP/ADP ratios in the intact liver cell

1984 ◽  
Vol 220 (2) ◽  
pp. 371-376 ◽  
Author(s):  
S Soboll ◽  
H J Seitz ◽  
H Sies ◽  
B Ziegler ◽  
R Scholz
Keyword(s):  
Liver Cell ◽  
Adenine Nucleotide ◽  
Intact Cell ◽  
Inhibitory Effect ◽  
Fatty Acyl ◽  
Fed State ◽  
Physiological Relevance ◽  
Chain Acyl ◽  
Long Chain

The effect of long-chain acyl-CoA on subcellular adenine nucleotide systems was studied in the intact liver cell. Long-chain acyl-CoA content was varied by varying the nutritional state (fed and starved states) or by addition of oleate. Starvation led to an increase in the mitochondrial and a decrease in the cytosolic ATP/ADP ratio in liver both in vivo and in the isolated perfused organ as compared with the fed state. The changes were reversed on re-feeding glucose in liver in vivo or on infusion of substrates (glucose, glycerol) in the perfused liver, respectively. Similar changes in mitochondrial and cytosolic ATP/ADP ratios occurred on addition of oleate, but, importantly, not with a short-chain fatty acid such as octanoate. It is concluded that long-chain acyl-CoA exerts an inhibitory effect on mitochondrial adenine nucleotide translocation in the intact cell, as was previously postulated in the literature from data obtained with isolated mitochondria. The physiological relevance with respect to pyruvate metabolism, i.e. regulation of pyruvate carboxylase and pyruvate dehydrogenase by the mitochondrial ATP/ADP ratio, is discussed.

Recovery of ventricular function in reperfused ischemic rat hearts exposed to fatty acids

1985 ◽  
Vol 249 (3) ◽  
pp. H492-H497 ◽  
Author(s):  
K. Ichihara ◽  
J. R. Neely
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Adenine Nucleotide ◽  
Recovery Of Function ◽  
Creatine Phosphate ◽  
Mechanical Function ◽  
Tissue Levels ◽  
Rat Hearts ◽  
Chain Acyl ◽  
Long Chain

The relationship between tissue levels of fatty acid metabolites in ischemic and reperfused hearts and recovery of mechanical function of these hearts on reperfusion was studied. Isolated rat hearts were exposed to global ischemia for periods up to 60 min under various conditions of coronary flow, O2 supply, and fatty acid concentrations and were then reperfused for either 15 or 30 min under aerobic conditions both with and without fatty acids present. Tissue levels of ATP, creatine phosphate, long-chain acyl CoA, and long-chain acyl carnitine were determined at the end of the ischemic and reperfusion periods. In some experiments K+ arrest during ischemia was used to prevent adenine nucleotide depletion both in the absence and presence of high fatty acids. Although the ability of these hearts to recover their preischemic mechanical function varied from 8 to 90% and tissue levels of acyl CoA and acyl carnitine during ischemia varied from 3- to 10-fold depending on the condition, no correlation was found between the recovery of function during reperfusion and either the presence of fatty acid or high levels of tissue long-chain acyl CoA and carnitine esters during ischemia.

Fatty acid oxidation by isolated perfused working hearts of aged rats.

1977 ◽  
Vol 232 (3) ◽  
pp. E258 ◽  
Author(s):  
G M Abu-Erreish ◽  
J R Neely ◽  
J T Whitmer ◽  
V Whitman ◽  
D R Sanadi
Keyword(s):  
Adenine Nucleotide ◽  
Acid Oxidation ◽  
Tissue Mass ◽  
Chain Acyl ◽  
Pressure Development ◽  
Heart Preparation ◽  
Old Rats ◽  
Total Carnitine ◽  
Long Chain

It has been reported that mitochondria isolated from hearts of old rats have lower respiratory activity than mitochondria from young rats. In order to determine the physiological correlates of these changes, the metabolism of hearts from young and old rats has been compared in a perfused working heart preparation. The oxidation of [14C]palmitate to 14CO2, oxygen consumption, and nucleotide levels were measured under different cardiac workloads. The hearts from old animals performed less cardiac work and utilized less oxygen and palmitate in proportion to tissue mass, but the ratio of oxygen consumed to pressure developed was unaltered. There was a small but significant decrease in cardiac efficiency expressed as the ratio between the rate of oxygen consumed and ventricular pressure development. Tissue levels of total carnitine and long-chain acylcarnitine derivatives were greatly reduced in the older heart without significant change in free CoA, acetyl-CoA, or long-chain acyl-CoA. The adenine nucleotide levels were not significantly different in the two groups. The results appear consistent with the in vitro studies on isolated mitochondria.

scholarly journals Interaction of acyl-CoA binding protein (ACBP) on processes for which acyl-CoA is a substrate, product or inhibitor

1993 ◽  
Vol 292 (3) ◽  
pp. 907-913 ◽  
Author(s):  
J T Rasmussen ◽  
J Rosendal ◽  
J Knudsen
Keyword(s):  
Feedback Inhibition ◽  
Adenine Nucleotide ◽  
Binding Protein ◽  
Point Of View ◽  
Beta Oxidation ◽  
Fatty Acid Binding ◽  
Triacylglycerol Synthesis ◽  
Chain Acyl ◽  
Pass Through ◽  
Long Chain

It is shown that acyl-CoA binding protein (ACBP), in contrast with fatty acid binding protein (FABP), stimulates the synthesis of long-chain acyl-CoA esters by mitochondria. ACBP effectively opposes the product feedback inhibition of the long-chain acyl-CoA synthetase by sequestration of the synthesized acyl-CoA esters. Feedback inhibition of microsomal long-chain acyl-CoA synthesis could not be observed, due to the formation of small acyl-CoA binding vesicles during preparation and/or incubation. Microsomal membrane preparations are therefore unsuitable for studying feedback inhibition of long-chain acyl-CoA synthesis. ACBP was found to have a strong attenuating effect on the long-chain acyl-CoA inhibition of both acetyl-CoA carboxylase and mitochondrial adenine nucleotide translocase. Both processes were unaffected by the presence of long-chain acyl-CoA esters when the ratio of long-chain acyl-CoA to ACBP was below 1, independent of the acyl-CoA concentration used. It is therefore not the acyl-CoA concentration as such which is important from a regulatory point of view, but the ratio of acyl-CoA to ACBP. The cytosolic ratio of long-chain acyl-CoA to ACBP was shown to be well below 1 in the liver of fed rats. ACBP could compete with the triacylglycerol-synthesizing pathway, but not with the phospholipid-synthesizing enzymes, for acyl-CoA esters. Furthermore, in contrast with FABP, ACBP was able to protect long-chain acyl-CoA esters against hydrolysis by microsomal acyl-CoA hydrolases. The results suggest that long-chain acyl-CoA esters synthesized for either triacylglycerol synthesis or beta-oxidation have to pass through the acyl-CoA/ACBP pool before utilization. This means that acyl-CoA synthesized by microsomal or mitochondrial synthetases is uniformly available in the cell. It is suggested that ACBP has a duel function in (1) creating a cytosolic pool of acyl-CoA protected against acyl-CoA hydrolases, and (2) protecting vital cellular processes from being affected by long-chain acyl-CoA esters.

Adenine nucleotide transport during cardiac ischemia

1981 ◽  
Vol 241 (5) ◽  
pp. H663-H671 ◽  
Author(s):  
K. F. LaNoue ◽  
J. A. Watts ◽  
C. D. Koch
Keyword(s):  
Adenine Nucleotide ◽  
Mitochondrial Protein ◽  
Heart Cells ◽  
Mitochondrial Matrix ◽  
Isolated Mitochondria ◽  
Palmitoyl Carnitine ◽  
Chain Acyl ◽  
Acyl Coenzyme A ◽  
Adenine Nucleotide Transport ◽  
Long Chain

The suggestion that long-chain acyl coenzyme A (CoA) derivatives may inhibit mitochondrial adenine nucleotide transport in heart cells during ischemia has been reevaluated. The effectiveness of media palmitoyl-CoA as an inhibitor is a function of mitochondrial protein and media adenine nucleotide concentrations. Extrapolation to the protein and adenine nucleotide levels of the cardiac cell suggest that physiological concentrations of cytosolic long-chain acyl-CoA would not inhibit adenosine 5'-triphosphate (ATP) transport. Palmitoyl-CoA was varied in the mitochondrial matrix by incubating the isolated mitochondria with and without palmitoyl carnitine. Intramitochondrial nucleotides were depleted by incubating the isolated mitochondria for various periods of time with arsenite and phosphate. Even at low substrate (matrix ATP) concentrations, no palmitoyl-CoA inhibition of ATP transport could be demonstrated. Further experiments showed that endogenous nucleotide levels are significantly depleted in mitochondria isolated from hearts made ischemic for 30-90 min. Since mitochondrial adenine nucleotide transport occurs by an exchange mechanism, this depletion of the internal pool of nucleotides from ischemic heart mitochondria may result in an irreversible diminution of ATP transport.

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