Glutamate degradation in the ischemic dog heart: contribution to anaerobic energy production.
The present study investigated the conversion of amino acids to succinate and the contribution of this pathway to anaerobic energy production during regional ischemia in the dog heart in situ. The relation between regional myocardial blood flow, estimated by the tracer microsphere technique, and myocardial contents of metabolites (glutamate, alanine, succinate, lactate) as well as their local arterio-venous differences (A-V) were determined. During 30 min of coronary artery occlusion, myocardial glutamate decreased from 2.3 mumol/g wet wt in control tissue to 1.2 mumol/g wet wt in severely ischemic areas, while aspartate was unaffected. Myocardial alanine increased in a 1: 1 stoichiometry compared to glutamate, and succinate accumulated. During control perfusion (118 mmHg), A-V of lactate, succinate and glutamate were +470, -0.7 and -3.9 nmol/ml, respectively. Stepwise reduction of perfusion pressure led to the release of lactate and succinate from the underperfused area; extraction of glutamate occurred at the lowest perfusion pressure investigated (34 mmHg; A-V: -500, -10.4 and +4.2 nmol/ml, respectively). The data indicate that during regional ischemia in vivo, succinate is synthetized exclusively from glutamate via 2-oxo-glutarate, following transamination with glycolytic pyruvate yielding alanine, while the contribution of aspartate is negligible. Using tissue levels of glutamate and lactate together with the local arterio-venous concentration differences of these compounds, it can be estimated that degradation of glutamate delivers 20% of the ATP generated by substrate level phosphorylation reactions. Thus energy production by the glutamate degradation pathway is significant in vivo under conditions of flow deprivation.
Wiesner
R J
RJ
Institut für Zoologie, Universität Düsseldorf, Federal Republic of Germany.
Deussen
A
A
Borst
M
M
Schrader
J
J
Grieshaber
M K
MK
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000693:Anaerobiosis; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D004734:Energy Metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption
D005971:Glutamates; D007773:Lactates; D019344:Lactic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate