Chem Path: Uric acid metabolism and gout Flashcards
What are the 3 purines in our body?
Adenosine, Guanosine and Inosine
What are 3 functions of purines?
Genetic code A & G
Second messengers for hormone action cAMP
Energy transfer - ATP
How are purines catabolised?
Purines are converted to hypo xanthines.
Hypo xanthines are converted to xanthines by xanthine oxidase
Xanthines are converted to urate by the same enzyme
What happens to urate
They are insoluble so they just circulate, almost always on the brink of conversion to uric acid crystals
Which joint is most often first affected in gout?
first metatarso phalangeal joint
What does Fractional Excretion of Uric Acid (FEUA) mean
Urate is freely excreted in the renal tubules. But by the end of PCT 90% of it has been reabsorbed
What are the 2 ways purines are metabolised?
De novo - Synthesised from scratch
Salvage pathway - They are recycled and this is energy efficient
Which purine synthesis pathway is preferred by the body cells?
Most of them prefer salvage pathway, EXCEPT the bone marrow, which has such a high cell turnover rate that it prefers the de novo pathway
What is the rate limiting step in the de novo pathway
PAT enzyme
It converts PPRP to GMP and AMP
GMP and AMP exert a negative feedback effect on PAT while PPRP exerts a positive feedback effect on PAT
What is a crucial enzyme in the salvage pathway?
HPRT/HGPRT
What is Lesch Nyhan syndrome
X linked disease
Complete deficiency of HGPRT/HPRT
How does Lesch Nyhan syndrome present?
Normal at birth Developmental delay shows at 6 months Choreiform movements Spasticity and UMN problems Mental retardation Self mutilation Hyperuricaemia
Why does Lesch Nyhan syndrome cause problems?
Since there is a deficiency of HPRT, PPRP accumulates, exerting more positive feedback on the salvage pathway and since there is no production on AMP and GMP, there is no negative feedback on the pathway to stop it. So the de novo pathway takes over, producing more urate.
Summarise the causes of hyperuracaemia?
Increased urate production:
- Primary
- Lesch Nyhan
- Secondary
- Myeloproliferative diseases
- Lymphoproliferative diseases
- Severe psoriasis
- Gaucher’s
- Chronic haemolytic anaemia
Decreased urate excretion:
- Primary
- FJHN
- Secondary
- CKD
- Lead poisoning
- Down’s
- Aspirin
- Diuretics
What is gout
Accumulation of monosodium urate crystals - Crystal arthropathy
