Question

Dihydrofolate reductase and thymidylate synthetase are major targets for anticancer drugs because:

a. These enzymes are unique to cancer cells

b. Cancer cells are very dependent upon the activities of these enzymes

c. These enzymes donate one-carbon groups

d. Cancer cells lack sufficient amounts of these enzymes

The formation of citrate from oxaloacetate and acetyl CoA is regulated by …

a. Glucose, acidic acid and ATP

b. Malate, NADH and FAD

c. ATP, NADH and citrate

d. This step is not regulated at all.

The oxidation of succinyl-CoA produces:

a. The same amount of ATP as the oxidation of malate.

b. Less ATP than the oxidation of malate.

b. More ATP than the oxidation of malate.

d. No ATP at all but requires activation through ATP hydrolysis.

Which of the following enzymes is active during oxidative phosphorylation?

a. Cytochrome oxidase

b. Lactate dehydrogenase

c. Glycogen Synthase

d. Fumarase

Answer 1

1. b. cancer cells are very dependent upon the activities of these enzymes

2. c. ATP, NADH and citrate

3. c. More ATP than oxidation of malate

4. a. Cytochrome oxidase.

Discussion and explanation :

1. Cancer is characterized by abnormally uncontrolled cell divisions (mitosis) to produce neoplastic cells. Cell cycle is depicted below :

We can see that, every cell will need to synthesise DNA during S phase of cell cycle before progressing for cell division. Many anticancer drugs inhibit this DNA synthesis by inhibiting enzymes providing raw material for DNA synthesis. Two such enzymes are thymidylate synthase and Dihydrofolate reductase involved in the synthesis of deoxythymidine monophosphate (dTMP) from deoxyuridine monophosphate (dUMP), synthesis can be depicted as below:

Usually, these enzymes are very much active in cancer cells to synthesise required DNA. So, anticancer drugs target these enzymes to inhibit DNA synthesis and thus halt uncontrolled cell divisions.

2. 3. and 4. Pyruvate produced by glycolysis is acted upon by pyruvate dehydrogenase complex to form acetyl CoA under aerobic condition to enter citric acid cycle. Acetyl CoA reacts with oxaloacetate to form citrate (citric acid), a reaction catalysed by citrate synthase. This enzyme is allosterically inhibited by ATP, NADH and citrate.

As we can see oxidation of succinyl CoA produces one NADH and one FADH2 which undergo oxidative phosphorylation to produce 3 ATPs per NADH and 2 ATPs per FADH2. Thus oxidation of succinyl CoA will produce 5 ATPs after oxidative phosphorylation.

Oxidation of malate will produce only one NADH which is equivalent to 3 ATPs.

Hence oxidation of succinyl CoA will produce more ATP than oxidation of malate.

Oxidative phosphorylation is processing of NADH and FADH2 through Electron transport chain to produce ATP. Components (including cytochrome oxidase) are depicted below: