Feed the animals allopurinol. Gout is caused when uric acid precipitates out in the joints due to excessive levels of uric acid. SO, allopurinol inhibits the enzyme xanthine oxidase, blocking the production of uric acid. It also binds to free PRPP, reducing the level of PRPP and reducing the rate of purine biosynthesis.

2. Why would feeding the animals 15N glycine determine whether the symptoms are caused by a defect in the de novo purine synthesis?

The source of every atom in the purine molecule has been derived. So, if you feed the animal heavy glycine, and the marker shows up in the uric acid, then the uric acid is coming from purine that was de novo synthesized from the heavy glycine.

3. Some animals have high levels of orotic acid in the urine (orotic aciduria). These animals are anemic and have stunted growth due to a defect in orotidylate decarboxylase. What treatment do you recommend and why?

To overcome a defect in orotidylate decarboxylate, you should feed the animal UMP, because that's what the defect is preventing from being made. UMP will also feed back negatively on the initial step of pyrimidine biosynthesis.

4. What is the effect of blocking TATA-binding protein from binding to the TATA box?

The first and probably rate limiting step in transcriptional initiation is the binding of TBP to the TATA box. RNA polymerase requires interaction with proteins that bind to the promoter because it can't recognize DNA directly. Once TBP binds to the TATA box, a series of other proteins bind as well, and after TF-IIE, IIH, and IIJ join the initiation complex, and then initiation can proceed with the addition of ribonucleotide triphosphates.

5. How do leucine zipper domains in transcription factors mediate protein dimerization?

Leucine zippers are made of an amphipathic alpha helix with leucine residues occuring every 7 amino acids. These leucines all face the same side of the helix. Proteins dimerize via their leucine zippes and then bind to DNA via adjacent basic regions.