A histological section of the left ventricle of a deceased 28-year-old male shows classic contraction band necrosis of the myocardium. Biological specimens confirm the presence of cocaine and metabolites. Activity of which of the following enzymes was most likely increased in the patient's myocardial cells sholy prior to his death?
Cocaine causes contraction band necrosis by blocking the reuptake of norepinephrine, resulting in excessive vasoconstriction of coronary vessels, leading to ischemia and infarction of hea tissue. Under these pathological conditions, myocardial cells switch to anaerobic metabolism and therefore glycolysis becomes the sole source of ATP substrate-level phosphorylations by phosphoglycerate kinase and pyruvate kinase. Phosphofructokinase-1 (PFK-1) is the rate-limiting enzyme of glycolysis, and its activity would therefore be increased. Phosphoenolpyruvate carboxykinase is a regulatory enzyme in gluconeogenesis, which is induced by coisol, epinephrine, and glucagon. It functions in the hepatic synthesis of glucose when energy levels from beta-oxidation of fatty acids are adequate. Pyruvate dehydrogenase produces acetyl-CoA from pyruvate and coenzyme A, bridging glycolysis and the Krebs cycle. It requires 5 cofactors, including NAD and FAD, which would no longer be produced by the electron transpo under hypoxic conditions, decreasing its activity. Succinate dehydrogenase is a key enzyme of the Krebs cycle, producing a reduced equivalent of FAD to feed into the electron transpo chain. It is also known as Complex II. The Krebs cycle only functions if oxygen is in appropriate concentrations since it is regulated by the levels of NADH, which is only consumed by the electron transpo chain if there is enough oxygen. The absence of oxygen leads to an accumulation of NADH and a subsequent decrease in the enzyme activities of the Krebs cycle. Ref: Bender D.A., Mayes P.A. (2011). Chapter 20. Gluconeogenesis & the Control of Blood Glucose. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper's Illustrated Biochemistry, 29e.
Phosphoenolpyruvate carboxykinase
Phosphofructokinase-1
Pyruvate dehydrogenase
Succinate dehydrogenase