Main Menu

During acute myocardial infarction, the oxygen supply to an area of heart is reduced forcing the cardiac muscle cells to switch to anaerobic oxidation. Under this condition the activity of which of the following enzymes is increased by the increasing concentration of AMP?

A.  Phosphofructokinase-1

B.  Pyruvate kinase

C.  Citrate synthase

D.  Lactate dehydrogenase

E.  Succinate dehydrogenase

The correct answer is- A) Phosphofructokinase-1.

Lactate dehydrogenase is not the right option, Although the level of Lactate dehydrogenase rises in circulation after myocardial injury but it is not the enzyme that is affected by the increasing concentration of AMP.

Basic concept

AMP, a marker of low energy state, is a positive allosteric modifier for Phosphofuctokinase-1,  which is a rate limiting enzyme of glycolysis. Phospho fructokinase is the “valve” controlling the rate of glycolysis.  

ATP is an allosteric inhibitor of this enzyme.

In the presence of high ATP concentrations, the Km for fructose-6-phosphate is increased, glycolysis thus “turns off.” ATP elicits this effect by binding to a specific regulatory site that is distinct from the catalytic site. AMP reverses the inhibitory action of ATP, and so the activity of the enzyme increases when the ATP/AMP ratio is lowered. In other words, glycolysis is stimulated as the energy charge falls, or the AMP concentration rises.

Phosphofructokinase-1 is also regulated by D-fructose-2,6-bisphosphate, a potent allosteric activator that increases the affinity of phosphofructokinase-1 for the substrate fructose-6-phosphate. Stimulation of phosphofructokinase is also achieved by decreasing the inhibitory effects of ATP. Fructose-2,6-bisphosphate increases the net flow of glucose through glycolysis by stimulating phosphofructokinase-1 and, by inhibiting fructose-1,6-bisphosphatase, the enzyme that catalyzes this reaction in the opposite direction.

AMP and Fructose 2,6 Bisphosphate are thus positive allosteric modifiers of Phosphofructokinase-1 (PFK-I), whereas ATP and Citrate are negative modifiers (Figure-1)

Citrate inhibits phosphofructokinase by enhancing the inhibitory effect of ATP.

Inhibition of glycolysis by citrate ensures that glucose will not be committed to these activities if the citric acid cycle is already saturated.

 Regulation of PFK-1

Figure-1- Phosphofructokinase-1 is regulated primarily by the energy needs of the cells. During the low energy conditions, glycolysis is stimulated to compensate for the energy. Reverse occurs in the presence of excess ATP (high energy state), the glycolysis is turned off.

Acute Myocardial infarction

Myocardial infarction (MI) is the irreversible necrosis of heart muscle secondary to prolonged ischemia. This usually results from an imbalance of oxygen supply and demand. This usually results from plaque rupture with thrombus formation in a coronary vessel, resulting in an acute reduction of blood supply to a portion of the myocardium.
The reduction of blood supply causes the change of aerobic mode of glycolysis to anaerobic, as a result lactate is the end product of glycolysis.

Lactate dehydrogenase(LDH) catalyzes the reversible conversion of pyruvate and lactate.


Figure-2- Reaction showing the interconversion of pyruvate and lactate.

The appearance of LDH in the circulation generally indicates myocardial necrosis. It begins to rise in 12 to 24 hours following MI, and peaks in 2 to 3 days, gradually dissipating in 5 to 14 days.

Measurement of LDH isoenzymes is necessary for greater specificity for cardiac injury. There are 5 isoenzymes (1 through 5). Ordinarily, isoenzyme 2 is greater than 1, but with myocardial injury, this pattern is “flipped” and 1 is higher than 2.

LDH-5 from liver may be increased with centrilobular necrosis from passive congestion with congestive heart failure following ischemic myocardial injury.

 As regards other options

B.  Pyruvate kinase- It catalyzes the conversion of phosphoenolpyruvate to pyruvate, the last step of glycolysis.  AMP affect the activity of this enzyme also, but this is not a rate limiting enzyme of Glycolysis.

C.  Citrate synthase-catalyzes the condensation of Acetyl co A with oxaloacetate to form Citrate, the first step of TCA cycle.

D.  Lactate dehydrogenase- catalyzes the interconversion of pyruvate and lactate.

E.  Succinate dehydrogenase  is an enzyme of TCA cycle, it catalyzes the conversion of succinate to fumarate.

Thus the most appropriate answer is Phosphofructokinase-1, which is affected by the rising concentration of AMP to stimulate the overall pathway of Glycolysis.

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!