Question

Discuss the following enzymes: hexokinase, pyruvate dehydrogenase, ATP synthase and phosphofructokinase.

-How do these enzymes interact with their substrates and catalyze reactions?

-What is unique about each type of enzyme and why are each of the enzymes suited to the specific reactions which they catalyze including major points of regulation (enzyme catalysis, the mechanism of interaction of enzymes with their substrates and the effect of regulators/inhibitors on enzymes)?

-What is the organization of the active site for each enzyme? Are any of these enzymes considered cellular motors? Why?

Answer 1

1. Hexokinase is the initial enzyme of glycolysis, catalyzing the phosphorylation of glucose by ATP to glucose-6-P. It is one of the rate-limiting enzymes of glycolysis.

Pyruvate dehydrogenase is an enzyme that catalyzes the reaction of pyruvate and CoA to give the acetylated Co A and carbon dioxide.

The function of ATP synthase is to synthesize ATP from ADP and inorganic phosphate (P_i) in the F₁ sector. This is possible due to energy derived from a gradient of protons which cross the inner mitochondrial membrane from the intermembrane space into the matrix through the F_o portion of the enzyme.

Phosphofructokinase (PFK) is the enzyme that controls the third step of glycolysis, the conversion of fructose-6-phosphate (F6P) into fructose-1,6-biphosphate (F1,6BP). It works by transferring a phosphate group from ATP to F6P. This is the slowest reaction in glycolysis and therefore is the rate-limiting step.

2. Hexokinase has a high affinity, thus a low Km, for glucose.

Pyruvate dehydrogenase complex is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the citric acid cycle.

ATP synthase is an F-ATPase. It consists of two main subunits, F_O and F₁, which has a rotational motor mechanism allowing for ATP production. Because of its rotating subunit, ATP synthase is a molecular machine.

In glycolysis, phosphofructokinase (PFK) is a key regulator of the overall reactions. It exists as a tetramer and each subunit has two binding sites for ATP. This enzyme catalyzes the first unique step in glycolysis, converting fructose-6-phosphate to fructose-1,6-bisphosphate.