Chem path 1s - Uric acid metabolism Flashcards
Name the three purines
Guanosine, Inosine and Adenosine
Name some of their roles (3)
Genetic code markers (A+G)
2nd messengers for hormones e.g. cAMP
Energy transfer ATP
Why do humans end up with a build up of urate?
In humans, the uricase gene is inactive and this usually breaks down urate to allantoin
Briefly outline the pathway from purines to urate
Purines –> Hypo-xanthine –> Xanthine by xanthine oxidase –> urate by xanthine oxidase
Name one reason why women are less prone to getting gout compraed to men
Women have lower monosodium urate plasma concentrations
With increase in temperature and decrease in pH, what happens to the solubility of MSU?
Goes down. Hence, the MTP which is peripheral and cooler, more likely to get gout
What is the fractional excreted uric acid (FEUA)?
~10% from kidneys, 90% of urea is reabsorbed
Where in the kidneys is urea reabsorbed and secreted?
PCT
The deficiency of which enzyme results in Lesch-nyhan syndrome?
HGPRT
What are some signs and symptoms of Lesch-Nyhan
6/12 developmental delay 12/12 choreiform movements Self-mutilation (1-16 yrs) in 85% Spasticity, mental retardation hyperuricaemia
Outline the biological basis of lesch-nyhan
Deficiency of HGPRT –> no conversion of guanine to GMP and no hypoxanthine to IMP. As there is less IMP and GMP there is less inhibitory feedback to PAT. De novo synthesis goes into overdrive –> build up of IMP –> abundance of urate. Also increased PPRP driving further positive feedback of PAT.
What are the two main pathways of purine sysnthesis? Which of these is most common?
De novo synthesis and salvage pathway. Salvage pathway most common.
All cells of body require purine sysnthesis except which?
RBCs
In which part of the body is de novo synthesis of purines alse used?
in Bone marrow
What is the key enzyme in de novo synthesis and which is the key enzyme in salvage pathway?
De novo - PAT (Rate limiting step)
Salvage - HGPRT
