title: Effects of ischemia and reperfusion on pyruvate dehydrogenase activity in isolated rat hearts.
abstract: The effects of myocardial ischemia and reperfusion on pyruvate dehydrogenase (PDH) activity were studied in isolated rat hearts. PDH remained largely (80%) in the active form during 10 min of whole heart ischemia in hearts receiving 11 mM glucose as substrate. With reperfusion, PDH was converted to the inactive form (45% by 2 min) and then returned slowly to control levels. Addition of pyruvate (10 mM) to the glucose containing perfusate during reperfusion prevent the reperfusion inactivation of PDH (96% active). The maintenance of a high percent of PDH in the active form during ischemia occurred in spite of high mitochondrial ratios of NADH/NAD and acetyl CoA/CoA and was related to a very low mitochondrial ATP/ADP ratio. The low ATP and high ADP would restrict PDH kinase phosphorylation and inactivation of PDH during ischemia. Reperfusion resulted in a rapid increase in mitochondrial ATP/ADP ratio and the increased availability of ATP as substrate for the kinase coupled with continued high levels of NADH and acetyl CoA which stimulate kinase activity may have accounted for the early inactivation of PDH with reperfusion. Addition of pyruvate to the perfusate probably inhibited the PDH kinase and prevent the reperfusion inactivation of PDH.
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D003326:Coronary Circulation; D004734:Energy Metabolism; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
chemical_list: D000214:Acyl Coenzyme A; D000227:Adenine Nucleotides; D002951:Citrates; D011768:Pyruvate Dehydrogenase Complex; D010725:Phosphocreatine; D009243:NAD; D019343:Citric Acid