Chem Path 1 - Gout Flashcards
What are the three main purines?
Adenosine
Guanine
Inosine
List three roles of purines.
Genetic code
Second messengers for hormone action (e.g. cAMP)
Energy transfer (e.g. ATP)
Describe the pathway of purine catabolism (include the enzymes and substrate names).
Purines to Hypoxanthine to Xanthine to Urate to Allantoin
Conversion from hypoxanthine to urate is performed by xanthine oxidase
Conversion of urate to allantoin is performed by uricase
What feature of the human purine catabolism pathway means that they are susceptible to a build-up of uric acid?
Uricase is inactive
Why are men more susceptible to gout than women?
They have higher average urate plasma concentrations
Which joint is most commonly affected by gout and why might this be?
1st metatarsophalangeal joint – found at the periphery of the body so is likely to be cooler (lower temperatures reduce the concentration at which urate precipitates out of solution)
What factor, other than temperature, affects the solubility of uric acid?
pH
Describe how the kidneys handle urate
The proximal convoluted tubule reabsorbs and secretes urate
Roughly what proportion of filtered urate will be found in the urine? What term is used to describe this?
10%
This is fractional excretion of uric acid (FEUA)
What is inosinic acid (IMP)?
An intermediate metabolite of AMP (adenylic acid) and GMP (guanylic acid)
Also a product of de novo purine synthesis
What are the two methods of purine synthesis? Which is predominant in most tissues?
De novo synthesis
Salvage pathway (PREDOMINANT)
Describe de novo purine synthesis. In which tissue is this dominant?
Metabolically demanding and inefficient
Only occurs when there is a high demand for purines (e.g. bone marrow)
What is the rate limiting step in the de novo purine synthesis pathway?
PAT
Describe the inhibitory and stimulatory controls on this enzyme.
AMP and GMP negatively regulate the activity of PAT
PPRP positively regulates the activity of PAT
What is the main enzyme of the salvage pathway? Describe its role.
HPRT (aka HGPRT)
It mops up partially catabolised purines and brings them back up the metabolic pathway to produce IMP and GMP
NOTE: hypoxanthine to IMP; guanine to GMP