Interaction between glutamine availability and metabolism of glycogen, tricarboxylic acid cycle intermediates and glutathione.
After exhaustive exercise, intravenous or oral glutamine promoted skeletal muscle glycogen storage. However, when glutamine was ingested with glucose polymer, whole-body carbohydrate storage was elevated, the most likely site being liver and not muscle, possibly due to increased glucosamine formation. The rate of tricarboxylic acid (TCA) cycle flux and hence oxidative metabolism may be limited by the availability of TCA intermediates. There is some evidence that intramuscular glutamate normally provides alpha-ketoglutarate to the mitochondrion. We hypothesized that glutamine might be a more efficient anaplerotic precursor than endogenous glutamate alone. Indeed, a greater expansion of the sum of muscle citrate, malate, fumarate and succinate concentrations was observed at the start of exercise (70% VO2(max)) after oral glutamine than when placebo or ornithine alpha-ketoglutarate was given. However, neither endurance time nor the extent of phosphocreatine depletion or lactate accumulation during the exercise was altered, suggesting either that TCA intermediates were not limiting for energy production or that the severity of exercise was insufficient for the limitation to be operational. We have also shown that in the perfused working rat heart, there is a substantial fall in intramuscular glutamine and alpha-ketoglutarate, especially after ischemia. Glutamine (but not glutamate, alpha-ketoglutarate or aspartate) was able to rescue the performance of the postischemic heart. This ability appears to be connected to the ability to sustain intracardiac ATP, phosphocreatine and glutathione.
Rennie
M J
MJ
Department of Anatomy & Physiology, University of Dundee, Dundee DD1 4HN, Scotland, UK. m.j.rennie@dundee.ac.uk
Bowtell
J L
JL
Bruce
M
M
Khogali
S E
SE
D000818:Animals; D002952:Citric Acid Cycle; D002986:Clinical Trials as Topic; D015444:Exercise; D005936:Glucans / Q000494:pharmacology; D018698:Glutamic Acid / Q000032:analysis / Q000097:blood / Q000378:metabolism; D005973:Glutamine / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism* / Q000652:urine; D006003:Glycogen / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D018763:Muscle Fatigue; D018482:Muscle, Skeletal / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion
D005936:Glucans; D005973:Glutamine; D018698:Glutamic Acid; D006003:Glycogen; D005978:Glutathione