Log out Go to App
Go to App

Learning Materials

Features

Discover

Chapter 26: Problem 4

Indicate which reactions of purine or pyrimidine metabolism are affected by the inhibitors (a) azaserine, (b) methotrexate, (c) sulfonamides, (d) allopurinol, and (e) 5 -fluorouracil.

Short Answer

Expert verified
Azaserine inhibits purine biosynthesis by inhibiting glutamine amidotransferase, methotrexate inhibits dihydrofolate reductase disrupting production of tetrahydrofolate needed for nucleotide synthesis, sulfonamides are competitive inhibitors of dihydropteroate synthase intervening in nucleotide synthesis in bacteria, allopurinol inhibits xanthine oxidase blocking purine catabolism, and 5-Fluorouracil affects pyrimidine metabolism by inhibiting thymidylate synthase and interfering with RNA function.

Step by step solution

01

Azaserine

Azaserine is a glutamine analog that inhibits the enzyme glutamine amidotransferase, which is involved in purine biosynthesis. Specifically, it blocks the conversion of PRPP (5-phospho-D-ribosylamine) to Inosin-5'-monophosphate (IMP) by inhibiting the reaction catalyzed by this enzyme.
02

Methotrexate

Methotrexate acts as an inhibitor for dihydrofolate reductase, an enzyme that's implicated in the production of tetrahydrofolate, which is important in the synthesis of purines and pyrimidines. This inhibits the process of these nucleotides synthesis.
03

Sulfonamides

Sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthase, which catalyzes the synthesis of dihydropteroic acid, an intermediary formed during folate synthesis in bacterium, which is a precursor for purine and pyrimidine nucleotide synthesis. Therefore, sulfonamides can inhibit the purine and pyrimidine metabolism.
04

Allopurinol

Allopurinol is a structural analog of the base hypoxanthine. It inhibits xanthine oxidase, an enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid in the purine degradation pathway. Thus, allopurinol inhibits purine catabolism.
05

5-Fluorouracil

5-fluorouracil (5-FU) is incorporated into RNA and interferes with its function. Importantly, it also inhibits thymidylate synthase, an enzyme that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), a crucial step in DNA synthesis. Hence, 5-FU disrupts pyrimidine metabolism.

Unlock Step-by-Step Solutions & Ace Your Exams!

  • Full Textbook Solutions

    Get detailed explanations and key concepts

  • Unlimited Al creation

    Al flashcards, explanations, exams and more...

  • Ads-free access

    To over 500 millions flashcards

  • Money-back guarantee

    We refund you if you fail your exam.

Start your free trial

Over 30 million students worldwide already upgrade their learning with Vaia!

One App. One Place for Learning.

All the tools & learning materials you need for study success - in one app.

Get started for free

Most popular questions from this chapter

Write a balanced equation for the oxidation of uric acid to glyoxylic acid, \(\mathrm{CO}_{2},\) and \(\mathrm{NH}_{3}\), showing each step in the process and naming all of the enzymes involved.

Since dUTP is not a normal component of DNA, why do you suppose ribonucleotide reductase has the capacity to convert UDP to dUDP?

Enzymes that bind phosphoribosyl-5-phosphate (PRPP) have a common structural fold, the PRT fold, which unites them as a structural family. PRT here refers to the phosphoribosyl transferase activity displayed by some family members. Typically, in such reactions, \(\mathrm{PP}_{\mathrm{i}}\) is displaced from PRPP by a nitrogen-containing nucleophile. Several such reactions occur in purine metabolism. Identify two such reactions where the enzyme involved is likely to be a PRT family member.

Illustrate the key points of regulation in (a) the biosynthesis of IMP, AMP, and GMP; (b) \(E .\) coli pyrimidine biosynthesis; and (c) mammalian pyrimidine biosynthesis.

Describe the underlying rationale for the regulatory effects exerted on ribonucleotide reductase by ATP, dATP, dTTP, and dGTP.
See all solutions

Recommended explanations on Chemistry Textbooks

Chemical Analysis

Read Explanation

Chemistry Branches

Read Explanation

Inorganic Chemistry

Read Explanation

Nuclear Chemistry

Read Explanation

Ionic and Molecular Compounds

Read Explanation

Kinetics

Read Explanation
View all explanations

What do you think about this solution?

We value your feedback to improve our textbook solutions.

Study anywhere. Anytime. Across all devices.

Sign-up for free