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A histological section of the left ventricle of a deceased 28-year-old white 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 shortly prior to his
death?
A. Phosphoenolpyruvate carboxykinase
B. Phosphofructokinase-1
C. Pyruvate dehydrogenase
D. Succinate dehydrogenase
E. Transketolase
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The correct answer is B. Cocaine causes contraction band necrosis by blocking the reuptake of norepinephrine,
resulting in excessive vasoconstriction of coronary vessels, leading to ischemia and infarction of heart tissue.
Under these pathological conditions, myocardial cells switch to anaerobic metabolism and therefore glycolysis
becomes the sole source of ATP via 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 (choice A) is a regulatory enzyme in gluconeogenesis, which is induced by
cortisol, epinephrine, and glucagon. It functions in the hepatic synthesis of glucose when energy levels from
beta-oxidation of fatty acids are adequate.
Pyruvate dehydrogenase (choice C) 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 transport under hypoxic conditions, decreasing its activity.
Succinate dehydrogenase (choice D) is a key enzyme of the Krebs cycle, producing a reduced equivalent of
FAD to feed into the electron transport 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 transport 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.
Transketolase (choice E) is a thiamine requiring enzyme of the non-oxidative half of the hexose monophosphate
shunt. The shuffling of sugars in the second half of this pathway results in the reentry of
glyceraldehyde-3-phosphate and fructose-6-phosphate into the glycolytic pathway. Transketolase activity in red
blood cells is used as a clinical marker of thiamine deficiency, markedly decreasing in disorders such as
Wernicke-Korsakoff syndrome.
