Uric acid metabolism

Question 1

What are the 3 main purines? (3)

Answer 1

Adenosine
Guanine
Inosine

Question 2

What are the 3 main functions of purines? (3)

Answer 2

Making up genetic code

Acting as second messengers

Energy stores

Question 3

What is the nature of urate? (4)

Answer 3

Insoluble

Circulates in the bloodstream at a concentration close to its limit of solubility

Acidic conditions and lower temperatures lower the limit of solubility (makes urate more likely to form crystals)

High fractional excretion of uric acid (FEUA = 10%, meaning 90% of the freely filtered uric acid is reabsorbed)

Question 4

How many pathways exist for purine metabolism and what are they? (2)

Answer 4

De novo pathway

Salvage pathway

Question 5

Which pathway predominates in purine metabolism in most tissues? (1)

Answer 5

Salvage pathway

Question 6

Which tissue predominantly uses the de novo pathway for purine metabolism? (1)

Answer 6

Bone marrow

Question 7

What is the precursor of AMP and GMP? (1)

Answer 7

Inosinic acid (IMP)

Question 8

What are the characteristics of the de novo pathway for purine metabolism? (4)

Answer 8

Inefficient

Begins with PRPP → 5-phosphoribosyl by PAT (phosphoribosyl-pyrophosphate amidotransferase)

PAT is the rate-limiting step
PAT is under:
- Negative feedback by GMP & AMP
- Positive feedback by PRPP

Question 9

What are the characteristics of the salvage pathway for purine metabolism? (2)

Answer 9

Efficient

Uses HGPRT (hypoxanthine-guanine phosphoribosyltransferase)

Question 10

What is the role of HGPRT in the salvage pathway? (1)

Answer 10

Recycles partially catabolized purines to remake IMP and GMP

Question 11

What is the main enzyme of the salvage pathway? (1)

Answer 11

HGPRT

Question 12

What is the rate-limiting enzyme for purine metabolism? (1)

Answer 12

PAT (phosphoribosyl-pyrophosphate amidotransferase)

Question 13

What happens to urate under acidic conditions and lower temperatures? (1)

Answer 13

The limit of solubility decreases, making urate more likely to form crystals.

Question 14

What are the two main degradation products of purines? (2)

Answer 14

Xanthine

Urate

Question 15

What is gout?

Answer 15

Gout is a form of microcrystal synovitis caused by the deposition of monosodium urate monohydrate in the synovium.

It is caused by chronic hyperuricaemia (uric acid > 450 µmol/l)

Question 16

What is hyperuricaemia?

Answer 16

(uric acid > 450 µmol/l)

Question 17

Acute management of gout?

Answer 17

NSAIDs or colchicine are first-line
the maximum dose of NSAID should be prescribed until 1-2 days after the symptoms have settled

gastroprotection (e.g. a proton pump inhibitor) may also be indicated

Question 18

How does colchine work for acute management of gout?

Answer 18

Inhibits microtubule polymerization by binding with tubulin interfering with mitosis

caution with renal impairment, reduce dose of eGFR is 10-50.

Question 19

Cholchine side effect?

Answer 19

diarrhoea

Question 20

Urate lowering therpay is used long term for gout, what is used?

Answer 20

Allopurinol

*colchicine cover to be used when starting allopurinol

2nd line is febuxostat