Chapter 26

Draw the purine and pyrimidine ring structures, indicating the metabolic source of each atom in the rings.

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.

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.

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

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

(Integrates with Chapters \(18-20 \text { and } 22 .)\) By what pathway(s) does the ribose released upon nucleotide degradation enter intermediary metabolism and become converted to cellular energy? How many ATP equivalents can be recovered from one equivalent of ribose?

Write a balanced equation for the conversion of aspartate to fumarate by the purine nucleoside cycle in skeletal muscle.

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.

(Integrates with Chapter \(15 .\) ) Unlike its allosteric counterpart glycogen phosphorylase (an \(\alpha_{2}\) enzyme), \(E\) coli ATCase has a heteromeric \(\left(\alpha_{6} \beta_{6}\right)\) organization. The \(\alpha\) -subunits bind aspartate and are considered catalytic subunits, whereas the \(\beta\) -subunits bind CTP or ATP and are considered regulatory subunits. How would you describe the subunit organization of ATCase from a functional point of view?

Write a balanced equation for the synthesis of dTMP from UMP and \(N^{5}, N^{10}\) -methylene-THF. Thymidylate synthase has four active-site arginine residues \(\left(\mathrm{Arg}^{23}, \mathrm{Arg}^{17 \mathrm{s}}, \mathrm{Arg}^{139}, \text { and } \mathrm{Arg}^{218}\right)\) involved in substrate binding. Postulate a role for the side chains of these Arg residues.