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Cancer Chemotherapeutic Agents Lecture 4 - Dr. M Casely-Hayford: Antimetabolites

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22 Questions

Which of the following enzymes is NOT essential for DNA synthesis?

RNA polymerase

Which of the following mechanisms does NOT describe the action of antimetabolites?

Inhibition of RNA function

Which of the following is NOT a common side effect of antimetabolite treatment?

Neurotoxicity

Which of the following B vitamins is NOT involved in DNA synthesis?

Vitamin B5 (Pantothenic acid)

Which of the following is NOT a reason for using antimetabolites in cancer treatment?

High selectivity for cancer cells

Which of the following is NOT a risk factor for folate deficiency?

Hyperthyroidism

Which compound acts as a one carbon source for dTMP synthesis?

N5, N10-methylene FH4

Which drug is a potent inhibitor of thymidylate synthase?

Methotrexate

Which compound is a coenzyme for essential biochemical transformations?

Folic acid

Which drug is known for its superior pharmacokinetic properties?

Methotrexate

Which compound is methylated by N5, N10-methylene FH4 to give dTMP?

Deoxyuridine monophosphate (dUMP)

Which drug inhibits DHFR and depletes the cofactor N5, N10-methylene FH4?

Methotrexate

What is the effect of depletion of the cofactor N5,N10-methylene FH4 on cellular processes?

It has the greatest effect on dTTP synthesis.

What is the difference between aminopterine and methotrexate?

Methotrexate has a methyl group at position R, while aminopterine does not.

What is the role of the sulfhydryl group in thymidilate synthase enzyme during dTMP synthesis?

It is involved in the formation of the ternary complex.

What is the mechanism of action of 5-fluorouracil (5-FU)?

5-FU inhibits the activity of thymidilate synthase enzyme.

How does the presence of the fluorine atom in 5-fluorouracil (5-FU) affect the electrophilicity of the C6 position in FdUMP?

The fluorine atom increases the electrophilicity of the C6 position.

What is the effect of abstraction of a C5-H by the N10 in the co-factor (Step 4 above) in the fluorinated ternary complex?

It is not possible in the fluorinated ternary complex.

What is the effect of the absence of dTMP on cellular processes?

It blocks DNA synthesis leading to cell death.

What makes 5-FU a particularly useful drug for the treatment of skin cancers?

It shows a high level of selectivity for cancer cells over normal skin cells.

What is the role of the cofactor N5,N10-methylene FH4 in the normal synthesis of dTMP?

It acts as a source of carbon atoms in the reaction.

What is the difference between deoxyuridine monophosphate (dUMP) and fluorinated deoxyuridine monophosphate (FdUMP)?

FdUMP has a fluorine atom at the C6 position, while dUMP does not.

Learn about antimetabolites, enzymes important in DNA synthesis, and the rationale for using drugs like 5FU and methotrexate in cancer treatment. Explore how these agents inhibit DNA synthesis or promote the incorporation of false nucleotides.

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