Chapter 32

Differentiate between the de novo synthesis of nucleotides and salvage-pathway synthesis.

What is the activated reactant in the biosynthesis of each of the following compounds? (a) Phosphoribosylamine (b) Carbamoylaspartate (c) Orotidylate (from orotate)

Differentiate between a nucleoside and a nucleotide.

Match the term on the right with the description on the left. (a) Excessive urate _____ (b) Lack of adenosine deaminase _____ (c) Lack of HGPRT _____ (d) Carbamoyl phosphate synthetase _____ (e) Inosinate _____ (f) Ribonucleotide reductase _____ (g) Lack of folic acid _____ (h) Glutamine phosphoribosyl transferase _____ (i) single ring _____ (j) Bicyclic ring _____ (k) Precursor to CTP _____ 1\. Spina bifida 2\. Precursor to both ATP and GTP 3\. Purine 4\. Deoxynucleotide synthesis 5\. UTP 6\. Lesch-Nyhan syndrome 7\. Immunodeficiency 8\. Pyrimidine 9\. Gout 10\. First step in pyrimidine synthesis 11\. Committed step in purine synthesis

Suppose that cells are grown on amino acids that have all been labeled at the \(\alpha\) carbons with \(^{13} \mathrm{C}\). Identify the atoms in cytosine and guanine that will be labeled with \(^{13} \mathrm{C}.\)

Tissue-culture cells were incubated with glutamine labeled with \(^{15} \mathrm{N}\) in the amide group. Subsequently, IMP was isolated and found to contain some is \(\mathrm{N}\). Which atoms in IMP were labeled?

What intermediate in purine synthesis will accumulate if a strain of bacteria is lacking each of the following biochemicals? (a) Aspartate (b) Tetrahydrofolate (c) Glycine (d) Glutamine

What is the biochemical basis of allopurinol treatment for gout?

Suppose that someone was suffering from a folate deficiency. What cells would you think might be most affected? Symptoms may include diarrhea and anemia.

Why are cancer cells especially sensitive to inhibitors of TMP synthesis?

Nucleotides play a variety of roles in the cell. Give an example of a nucleotide that acts in each of the following roles or processes. (a) Second messenger (b) Phosphoryl-group transfer (c) Activation of carbohydrates (d) Activation of acetyl groups (e) Transfer of electrons (f) Chemotherapy (g) Allosteric effector

Human beings contain two different carbamoyl phosphate synthetase enzymes. One uses glutamine as a substrate, whereas the other uses ammonia. What are the functions of these two enzymes?

You suspect that your pet duck has gout. Why should you think twice before administering a dose of allopurinol-laced bread?

Mutant cells unable to synthesize nucleotides by salvage pathways are very useful tools in molecular and cell biology. Suppose that cell A lacks thymidine kinase, the enzyme catalyzing the phosphorylation of thymidine to thymidylate, and that cell B lacks hypoxanthine-guanine phosphoribosyl transferase. (a) Cell A and cell B do not proliferate in a HAT medium containing hypoxanthine, aminopterin or amethopterin (methotrexate), and thymine. However, cell \(C\) formed by the fusion of cells \(A\) and \(B\) grows in this medium. Why? (b) Suppose that you wanted to introduce foreign genes into cell A. Devise a simple means of distinguishing between cells that have taken up foreign DNA and those that have not.

Many patients with glucose 6 -phosphatase deficiency have high serum levels of urate. Hyperuricemia can be induced in normal people by the ingestion of alcohol or by strenuous exercise. Propose a common mechanism that accounts for these findings.