Uric Acid Metabolism Flashcards
What are the 3 main purines?
Adenosine
Guanine
Inosine
In humans, which enzyme/gene is inactive which leads to problems in purine metabolism?
Uricase (gene)
Why does uric acid tend to precipitate in the metatarsophalangeal joint?
It is at the periphery of the body so it is cooler.
What is the benefit of high urate levels?
Protection against oxidative stress
What are the two main ways of making purines?
De novo metabolism Salvage pathway (recycling)
Which is the predominant purine metabolism pathway?
Salvage pathway
In what conditions will de novo purine metabolism occur?
Very high demand for purines, e.g. in the bone marrow
What is the enzyme in the rate-limiting step in de novo purine metabolism?
PAT
What is the main enzyme of the salvage pathway?
HGPRT
Which condition results due to HGPRT deficiency?
Lesch-Nyhan syndrome
What is the genetic inheritance of Lesch-Nyhan syndrome?
X-linked
What are the key clinical features of Lesch-Nyhan syndrome?
Normal at birth Developmental delay at 6 months Hyperuricaemia (which is very rare in children) Choreiform movements at 1 yera Spasticity Intellectual disability Self-mutilation
What is the biological effect of HGPRT deficiency?
Less IMP and GMP produced means less inhibition of PAT
De novo pathway goes into overdrive
Lots of IMP being produced
The IMP is shunted down the catabolic pathway to try and reduce the amount
Leads to an accumulation of urate
Furthermore, less guanine is converted to GMP so PPRP also builds up, further driving PAT
Fundamentally, how can hyperuricaemia be caused?
Increased urate production
Decreased urate excretion
Give three examples of conditions causing secondary hyperuricaemia due to increased production.
Myeloproliferative disorders
Severe psoriasis
Chronic haemolytic anaemia
