Nucleotide Metabolism 2

Question 1

Explain Salvage Pathway for purine nucleotides ?

Answer 1

• What: Recycling of products of nucleic acid breakdown
• Where: Salvage pathway occurs primarily in extrahepatic tissues, whereas de novo pathway occurs primarily in the liver
• How: From free bases (A, G)
• Who: APRT and HGPRT is responsible for most of the recycling
• How much: Salvage pathway accounts for 90% of daily purine nucleotide biosynthesis
• Why: Most purine bases are recycled rather than degraded. Salvage pathway requires less energy than de novo pathway for purine synthesis

Question 2

How are the purine nucleotides balanced ?

Answer 2

The quantity of uric acid produced is balanced by an equivalent quantity of de novo purine synthesis. Therefore, any increase in de novo purine production is balanced by a comparable increase in uric acid production

Question 3

What happens during intense exercise ?

Answer 3

• AMP deaminase converts AMP to IMP, releasing NH3
• Decreasing AMP levels shifts the equilibrium of adenylate kinase to produce more ATP for muscle contraction
• IMP can be recycled to AMP

Question 4

What does the reutilisation of hypoxanthine and guanine need ?

Answer 4

HGPRT

Question 5

Describe Lesch-Nyhan Syndrome ?

Answer 5

Lesch-Nyhan Syndrome is characterised by the deficiency of “hypoxanthine-guanine phosphoribosyl transferase (HGPRT)”, leads to accumulation of PRPP and uric acid, the condition is known as “Hyperuricemia”

Question 6

What is Hyperuricemia ?

Answer 6

This is the presence of high levels of uric acid/sodium urate crystals in the blood

Question 7

What is the upper end of the normal range of uric acid for women and men?

Answer 7

360 umol/L (6mg/dL) for women and 400 umol/L (6.8mg/dL) for men

Question 8

What does Allopurinol decrease ?

Answer 8

The amount of uric acid produced in the body. To treat and prevent bladder stones, it should be used with a diet that is low in purines.

Question 9

When do Purines tend to be generally higher ?

Answer 9

In high-protein foods. In the body, purines are converted to uric acid. Allopurinol blocks this conversion.

Question 10

How much of pyrimidine nucleotides are provided by the salvage pathway ?

Answer 10

30%

Question 11

Where does Pyrimidine salvage occur ?

Answer 11

At the level of nucleosides rather than free bases

- Note: Pyrimidine bases can be salvaged but the process is very slow

Question 12

Where do pyrimidine nucleosides travel and get taken up by ?

Answer 12

Pyrimidine nucleosides travel in the blood and are taken up by tissues

Question 13

What are Pyrimidines generally degraded to ?

Answer 13

Intermediates of carbon metabolism (for example, succinyl-CoA) and ammonia (NH4+)

Question 14

Defects in enzymes of pyrimidine degradation, results in ?

Answer 14

Increased levels of pyrimidines and neurological disorders

Question 15

What is 6 thioinosinic acid activated by ?

Answer 15

• Hypoxanthine - guanine phosphoribosyltransferase (HGPRT)

- inhibit enzymes involved in purine metabolism

Question 16

What would resistance do ?

Answer 16

• decrease HGPRT activity

- increase alkaline phosphatases that inactivate the toxic nucleotides

Question 17

What is a mercaptopurine analog of adenine and hypoxanthine ?

Answer 17

Azathioprine

Question 18

It is a prodrug that is ?

Answer 18

Converted first to 6 mercaptupurine (6-MP) which in turn can be converted to 6-mercaptopurine nucleotides leading to an inhibition of denovo purine synthesis

Question 19

What are the three enzymes that play a major role in the metabolism of azathioprine and mercaptopurine ?

Answer 19

1. Xanthine oxidase (XO)
2. Thiopurine methyltransferase (TPMT)
3. HGPRT