Biochemical derangements in ischemic myocardium: the role of carnitine.
The most important biochemical derangements in ischemic myocardium are the decrease of energy rich phosphates (ATP and phosphocreatine) and intracellular acidosis, both of which contribute to a rapid loss of the contractile function. How and to which extent the alterations of carbohydrate and lipid metabolism are involved in these derangements is briefly discussed. In conditions of oxygen restriction the synchronism between the cytosolic and mitochondrial phase of carbohydrate metabolism is disrupted and beta-oxidation of long chain fatty acids is prevented. Consequently less ATP and more lactate is produced and fatty acids accumulate together with their activation products, acyl CoA in particular. In ischemia free carnitine is also decreased and the carnitine dependent functions (acyl transfer across mitochondrial membrane and pyruvate and alpha ketoglutarate dehydrogenase stimulation) impaired. The meaning of the altered carnitine dependent functions is considered together with the possible (demonstrated and supposed) metabolic effects of carnitine administration in cardiac ischemia.
D000214:Acyl Coenzyme A / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D002333:Carnitine Acyltransferases; D003327:Coronary Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D014166:Transferases / Q000378:metabolism
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D014166:Transferases; D000217:Acyltransferases; D002333:Carnitine Acyltransferases; D000251:Adenosine Triphosphatases; D005947:Glucose; D002331:Carnitine