ChemPath 1S: Uric Acid Metabolism Flashcards
Name the purines
- Adenosine
- Guanosine
- Inosine
What do the purines act as?
- Genetic code markers (A & G)
- 2nd messengers for hormones (e.g. cAMP)
- Energy transfer (e.g. ATP)
What are the steps in purine catabolism i.e. breakdown and which enzymes are involved in each step?
Purines
→ hypo-xanthine (Xanthine Oxidase / XO)
→ Xanthine (XO)
→ Urate (Uricase)
→ Allantoin
N.B uricase is not present in humans, hence urate circulates in bloodstream
What are the features of allantoin?
- highly soluble
- freely excreted in urine
N.B. enzyme catabolising urate into allantoin (uricase) is not present in humans, hence allantoin is not present in human bloodstream or urine
What are the Monosodium Urate (MSU) plasma concentrations in men and women?
- Men = 0.12 - 0.42mmol/L
- Women = 0.12 - 0.36mmol/L
lower concentrations in women!
As temperature goes up, solubility (and thus, concentration) goes up
What proportion of urate is excreted by the kidneys? What happens to the rest?
- Fractional Excretion of Uric Acid (FEUA) ~10% from kidneys
- (90% of urate is reabsorbed)
What are the 2 ways of synthesising purines?
- de novo synthesis
- salvage pathway
Summarise the de novo synthesis of purines
green box = de novo synthesis of purines
N.B. guanylic acid = GMP, adenylic acid = AMP
Summarise the salvage pathway of purine synthesis
blue box curvy upward arrows = salvage pathway of purines
i.e. recycling purines using breakdown products
N.B. guanylic acid = GMP, adenylic acid = AMP
Summarise the features of the de novo synthesis of purines
- inefficient
- only done when high demand
- PAT enzyme is rate-limiting step
- Only dominant in the bone marrow, salvage pathway dominates in every other cell in the body
Summarise the features of the salvage pathway synthesis of purines
- highly efficient
- predominant pathway for purine synthesis
- H(G)PRT is the main enzyme involved in this
What is the rate limiting step in de novo purine synthesis?
PAT is the rate limiting enzyme
Summarise the components of the salvage pathway in purine synthesis
N.B. guanylic acid = GMP, adenylic acid = AMP, inosinic acid = IMP
These are all converted to guanine, adenosine and insosine respectively
What is Lesch Nyhan syndrome?
COMPLETE HGPRT Deficiency
N.B. HGPRT = Hypoxanthine-Guanine Phosphoibosyltransferase
What is the pattern of inheritance of Lesch Nyhan syndrome?
X linked recessive (predominantly affects males)
What is the aetiology of Lesch Nyhan syndrome?
Complete HPRT deficinecy
- HPRT is usually used to recycle hypoxanthine and guanine back into DNA synthesis
- Hence, lack of this enzyme → less production of IMP and GMP from hypoxanthine and guanine respectively
- → lack of IMP and GMP causes less feedback inhibition of PAT enzyme in de novo synthesis of purines pathway (dotted lines)
- → cells produce IMP along de novo pathway uncontrolled (producing IMP/inosinic acid just under green box)
- → IMP is shunted down the catabolic pathway (blue box)
- → uncontrolled breakdown of IMP into uric acid/urate
- PPRP also builds up (next to HPRT upwards arrow blue box) → driving further positive feedback of PAT
What are the causes of hyperuricaemia?
Tap effusion, what is the diagnosis?
- crystals are needle shaped, so already know that it’s gout
- Negative birefringence seen
- black and yellow arrows are direction of axis of the red compensator
- crystals appear yellow in same direction of arrow & blue perpendicular to arrow
Tap effusion, what is the diagnosis?
- crystals are rhombus shaped, so we already know that it is pseudogout
- POSITIVE birefringence seen
- black and yellow arrows are direction of axis of the red compensator
- crystals appear blue in same direction of arrow & yellow perpendicular to arrow
