Purine Nucleotides

Question 1

What is PRPP Synthetase?

Answer 1

Converts Ribose 5-Phosphate —> 5-Phosphoribosyl-1-pyrophosphate.

Question 2

What activates PRPP Synthetase? What inhibits?

Answer 2

Activate: Pi
Inhibit: IMP, AMP, GMP

Question 3

What activates PRPP Amidotransferase? Inhibits?

Answer 3

Activates: Elevated levels of PRPP
Inhibits: IMP, AMP, and GMP

Question 4

What is PRPP Amidotransferase?

Answer 4

FIRST enzyme in de novo purine biosynthesis

Question 5

What does hypoxanthine-guanine phosphoribosyl transferase (HGPRT)?

Answer 5

Converts Hypoxanthine –> IMP

Mutations in the HPRT1 gene cause Lesch-Nyhan syndrome. The HPRT1 gene provides instructions for making an enzyme called hypoxanthine phosphoribosyltransferase 1. This enzyme is responsible for recycling purines, a type of building block of DNA and its chemical cousin RNA. Recycling purines ensures that cells have a plentiful supply of building blocks for the production of DNA and RNA.
HPRT1 gene mutations that cause Lesch-Nyhan syndrome result in a severe shortage (deficiency) or complete absence of hypoxanthine phosphoribosyltransferase 1. When this enzyme is lacking, purines are broken down but not recycled, producing abnormally high levels of uric acid.

Question 6

What does Xanthine Oxidase?

Answer 6

Converts Hypoxanthine –> Xanthine

Question 7

What is Lesch Nyhan syndrome?

Answer 7

It is HGPRT deficiency! Causes an overproductive form of GOUT

Question 8

How does Purine Degradation work?

Answer 8

Excess purine nucleotides are degrade by a series of steps that lead to uric acid (which is then excreted into the urine)

Question 9

What happens when you have elevated levels of uric acid (hyperuricemia)

Answer 9

This can lead to gout!!

Question 10

What are ways you can treat gout?

Answer 10

1. Reduce uric acid synthesis at xanthine oxidase
2. Increase nucleotides (inhibit de novo pathway)
3. Renal clearance of elevated hypoxanthine and xanthine