Compartmentation of energy metabolism in atrial myocardium of patients undergoing cardiac surgery.
The parameters of oxidative phosphorylation and its interaction with creatine kinase (CK)- and adenylate kinase (AK)-phosphotransfer networks in situ were studied in skinned atrial fibers from 59 patients undergoing coronary artery bypass surgery, valve replacement/correction and atrial septal defect correction. In atria, the mitochondrial CK and AK are effectively coupled to oxidative phosphorylation, the MM-CK is coupled to ATPases and there exists a direct transfer of adenine nucleotides between mitochondria and ATPases. Elimination of cytoplasmic ADP with exogenous pyruvate kinase was not associated with a blockade of the stimulatory effects of creatine and AMP on respiration, neither could it abolish the coupling of MM-CK to ATPases and direct transfer of adenine nucleotides. Thus, atrial energy metabolism is compartmentalized so that mitochondria form functional complexes with adjacent ATPases. These complexes isolate a part of cellular adenine nucleotides from their cytoplasmic pool for participating in energy transfer via CK- and AK-networks, and/or direct exchange. Compared to atria in sinus rhythm, the fibrillating atria were larger and exhibited increased succinate-dependent respiration relative to glutamate-dependent respiration and augmented proton leak. Thus, alterations in mitochondrial oxidative phosphorylation may contribute to pathogenesis of atrial fibrillation.
Seppet
Evelin
E
Department of Pathophysiology, Human Genetics and Biology and Cardiovascular and Thoracic Surgery, Centre of Molecular and Clinical Medicine, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Eimre
Margus
M
Peet
Nadezhda
N
Paju
Kalju
K
Orlova
Ehte
E
Ress
Mati
M
Kõvask
Sirje
S
Piirsoo
Andres
A
Saks
Valdur A
VA
Gellerich
Frank N
FN
Zierz
Stephan
S
Seppet
Enn K
EK
D000227:Adenine Nucleotides / Q000737:chemistry; D000244:Adenosine Diphosphate / Q000737:chemistry; D000249:Adenosine Monophosphate / Q000737:chemistry / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry; D000263:Adenylate Kinase / Q000378:metabolism; D000328:Adult; D003402:Creatine Kinase / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D007700:Kinetics; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D010766:Phosphorylation; D011770:Pyruvate Kinase / Q000378:metabolism; D012119:Respiration; D013053:Spectrophotometry; D013386:Succinates / Q000378:metabolism; D013903:Thoracic Surgery; D013997:Time Factors
D000227:Adenine Nucleotides; D013386:Succinates; D018698:Glutamic Acid; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011770:Pyruvate Kinase; D003402:Creatine Kinase; D000263:Adenylate Kinase; D000251:Adenosine Triphosphatases; D010100:Oxygen