Week 6: Purine and Pyrimidine Metabolism

Question 1

Pyrimidine degradation

Answer 1

Products are soluble so can be excreted in the urine

Question 2

List of purines

Answer 2

GMP - Guanosine

AMP - Adenosine

Question 3

Degradation of GMP

Answer 3

GMP –> Guanine + Ribose

Question 4

Degradation of AMP

Answer 4

AMP –> Hypoxanthine + Ribose

Ribose is recycled to PRPP and back to nucleotide synthesis

Hypoxanthine + Guanine –> Xanthine -Xanthine Oxidase-> Uric Acid (pKa = 5.4 (Weak acid))

Question 5

What is the problem of uric acid?

Answer 5

since it is a weak acid, some are deprotonated and some are protonated, Protonated form is less soluble so this is a problem because the pKa is approaching neutrality in the urine and blood at 5.4

So, it doesn’t take a whole lot to precipitate because of the large amount of protonated form of uric acid

The precipitation is increased by temperature drops such as in the extremities becoming a few degrees colder and can form crystals (major location is big toe) Uric acid crystals AKA Gout or Gouty Arthritis

Question 6

How to inhibit GOUT

Answer 6

Inhibit Xanthine oxidase to prevent the degradation of Xanthine into uric Acid and preventing gout

Question 7

Allopurinol MOA

Answer 7

Inhibits Xanthine Oxidase preventing hypoxanthine from becoming Xanthine and Xanthine from becoming Uric Acid

This allows Hypoxanthine and xanthine to be excreted into the urine because they are more soluble than uric acid

Question 8

Describe the purpose of the salvage pathway

Answer 8

In order to produce GMP, AMP and the pyrimidine ring need amino acids, small molecules such as carbamoyl phosphate from the cytoplasm and a lot of reducing power to construct large molecules from smaller molecules. These molecules are energetically expensive!

Problem is we are now excreting these into the urine after degradation(removing ribose and modifying the substitutions around the ring structures)

The salvage pathway is to recapture the bases and reuse them if they are undamaged

Question 9

Describe the purine salvage pathway

Answer 9

guanine or Hypoxanthine (ribose cleaved off) + PRPP -HGPRT(Hypoxanthine Guanine Phosphoribosyl Transferase)-> IMP (inosine monophosphate) —–several reactions to either-> GMP or AMP

Now we can recapture the bases and don’t need to waste energy to remake them

Question 10

Disease of the purine salvage pathway

Answer 10

HGPRT is defective in Leish-Nyhan Syndrome so we have lost the ability to recover purines in the salvage pathway and leads to:

• Mental retardation
• Self-mutilation
• Also, develop gouty arthritis (because the salvage pathway prevents uric acid synthesis from hypoxanthine and xanthine

Question 11

What is Leish-Nyhan Syndrome?

Answer 11

HGPRT is defective in Leish-Nyhan Syndrome so we have lost the ability to recover purines in the salvage pathway and leads to:

• Mental retardation
• Self-mutilation
• Also, develop gouty arthritis (because the salvage pathway prevents uric acid synthesis from hypoxanthine and xanthine