Biochemistry · Metabolic pathway
Purine degradation and salvage !
Spare purines are turned into uric acid, which leaves in the urine; many of the bases are recycled before they get that far.
Updated 2026-11-01
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Key facts
- End product in humans: uric acid. We lack uricase, so blood urate is much higher than in most mammals.
- Xanthine oxidase performs the last two steps (hypoxanthine → xanthine → uric acid); allopurinol and febuxostat block it.
- Salvage: HGPRT recovers hypoxanthine and guanine (→ IMP, GMP) and APRT recovers adenine (→ AMP), both using PRPP.
- Parallel AMP route: AMP → adenosine (5'-nucleotidase) → inosine (adenosine deaminase, ADA). Its deficiency causes severe combined immunodeficiency.
- GMP follows: guanosine → guanine (PNP) → xanthine (guanase), joining the same final route.
In detail
- Salvage is cheap: one step with PRPP versus six high-energy bonds for de novo synthesis.
- The brain and lymphocytes depend heavily on salvage or de novo synthesis, which is why defects give neurological or immune symptoms.
- About two-thirds of urate is excreted by the kidney and the rest through the gut.
- In the kidney, the URAT1 transporter reabsorbs urate; it is the target of uricosuric drugs.
- Also called
- Purine catabolism
Regulation
- The pathway is controlled mainly by supply: more cell turnover or more dietary purine yields more uric acid.
- Salvage uses up PRPP; when it fails (HGPRT deficiency), leftover PRPP speeds up de novo synthesis.
The steps, one by one
- Step 1 · AMP deaminase (AMPD) irreversible AMP (adenylate) + H₂O → IMP + nh3Removes the amino group of AMP, leaving IMP; very active in muscle during exercise.If it fails: Muscle deficiency (AMPD1) is common and usually silent; sometimes it causes cramps with exercise.
- Step 2 · 5'-Nucleotidase irreversible IMP + H₂O → Inosine + phosphate (Pi)Removes the phosphate: the nucleotide becomes a nucleoside (inosine).If it fails: Serum 5'-nucleotidase rises in cholestasis.
- Step 3 · Purine nucleoside phosphorylase (PNP) Inosine + phosphate (Pi) ⇌ Hypoxanthine + Ribose 1-phosphateSplits the base from the sugar using phosphate, leaving free hypoxanthine.If it fails: PNP deficiency builds up dGTP in T cells: cellular immunodeficiency and low uric acid.
- Step 4 · Xanthine oxidase irreversible Hypoxanthine + o2 + H₂O → Xanthine + Hydrogen peroxideFirst oxidation: hypoxanthine becomes xanthine at the molybdenum centre.If it fails: Its deficiency (xanthinuria) lowers uric acid and forms xanthine stones. Hereditary xanthinuria →
- Step 5 · Xanthine oxidase irreversible Xanthine + o2 + H₂O → Uric acid + Hydrogen peroxideSecond oxidation by the same enzyme: xanthine becomes uric acid, the human end product.If it fails: Excess uric acid precipitates as urate crystals: gout and stones. Gout →
- Step 6 · Urate oxidase (uricase): absent in humans irreversible Uric acid + o2 + H₂O → Allantoin + CO₂ + Hydrogen peroxideThis step does not exist in humans: it is shown because recombinant uricase (rasburicase) is used as a drug.If it fails: Rasburicase is contraindicated in G6PD deficiency: the H₂O₂ it makes causes haemolysis and methaemoglobinaemia. Tumour lysis syndrome →
Clinical notes
- Gout: monosodium urate crystals in joints when urate exceeds its solubility limit.
- Tumour lysis syndrome: massive tumour cell death floods the pathway with purines and injures the kidney.
- HGPRT deficiency: Lesch-Nyhan syndrome (complete) or juvenile gout (partial).
- PNP deficiency: T-cell immunodeficiency with very low uric acid.
Related conditions
- Gout
- Kidney stones (urolithiasis)
- Lesch-Nyhan syndrome
- Adenosine deaminase deficiency (ADA-SCID)
- Tumour lysis syndrome
- Hereditary xanthinuria
Related
- Uric acid
- Hypoxanthine
- IMP (inosine monophosphate)
- Xanthine oxidase
- Adenosine deaminase (ADA)
- Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
- Adenine phosphoribosyltransferase (APRT)
- PRPP (phosphoribosyl pyrophosphate)
- De novo purine synthesis
- Drugs acting on nucleotide metabolism
Test yourself
Think of the answer, then tap the question to see it.
Why does allopurinol lower uric acid?
Its metabolite oxypurinol binds tightly to xanthine oxidase and blocks the pathway's last two steps.
Which enzymes recycle purine bases, and which co-substrate do they use?
HGPRT (hypoxanthine, guanine) and APRT (adenine); both use PRPP and form the nucleotide in one step.
Why do humans have higher urate than most mammals?
Uricase was lost in evolution: uric acid is the end product and is not converted to allantoin.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Purine catabolism (Reactome, 2026); Purine salvage (Reactome, 2026); Uric acid - blood : MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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