Learn / Metabolism
Metabolic pathways
Every FMK pathway as a clickable map. Pick one pathway to hammer it — next step, enzyme, regulator, cofactor, and the facts that get tested (NADPH and who needs it, rate-limiting steps, deficiencies) — or set it to all pathways for a mixed drill. Every answer says which enzyme and which pathway.
Purine degradation & uric acid
Nucleotides lose their phosphate (nucleotidase) and sugar (PNP) to free bases; adenosine is deaminated by ADA, guanine by guanine deaminase; hypoxanthine → xanthine → uric acid is xanthine oxidase twice. Humans lack urate oxidase, so the end product is insoluble uric acid — gout and stones. ADA deficiency is SCID because dATP shuts down ribonucleotide reductase in lymphocytes.
Click any metabolite on the map for its reactions. Source: FMK-08.1 Nucleic acid metabolism.
Reactions
| Step | Enzyme | Cofactors | Regulation |
|---|---|---|---|
| AMP → IMP | AMP deaminase | — | |
| AMP → Adenosine | 5′-Nucleotidase | — | |
| Adenosine → Inosine | Adenosine deaminase (ADA) ADA deficiency → SCID (AR): adenosine/deoxyadenosine accumulate → dATP ↑ → ribonucleotide reductase inhibited → no dNTPs → T, B AND NK cells die; recurrent infections, no thymic shadow, fatal by ~2 y untreated; enzyme replacement, transplant, gene therapy Adenosine deaminase (ADA) deficiency — SCID → |
— | |
| IMP → Inosine | 5′-Nucleotidase | — | |
| GMP → Guanosine | 5′-Nucleotidase | — | |
| Inosine → Hypoxanthine | Purine nucleoside phosphorylase (PNP) PNP deficiency — milder, predominantly T-cell immunodeficiency (B cells relatively spared); supportive care / transplant Purine nucleoside phosphorylase (PNP) deficiency → |
Pi → ribose-1-P | |
| Guanosine → Guanine | Purine nucleoside phosphorylase (PNP)Purine nucleoside phosphorylase (PNP) deficiency → | Pi → ribose-1-P | |
| Guanine → Xanthine | Guanine deaminase | — | |
| Hypoxanthine → Xanthine | Xanthine oxidaseGout →Allopurinol → | O₂ → H₂O₂ | − Allopurinol (hypoxanthine analog); Febuxostat |
| Xanthine → Uric acid (urine) | Xanthine oxidase ★Gout →Allopurinol → | O₂ → H₂O₂ | − Allopurinol; Febuxostat |
| Uric acid (urine) → Allantoin (not in humans) | Urate oxidase (uricase) — ABSENT in humansTumor lysis syndrome (TLS) →Rasburicase (recombinant urate oxidase) → | — |
Conditions that live on this map
Acute gout anti-inflammatory therapy (colchicine, NSAIDs, glucocorticoids)Adenosine deaminase (ADA) deficiency — SCIDAllopurinolGoutHyperuricemia — underexcretion (primary and secondary)Pseudogout (CPPD deposition)Purine nucleoside phosphorylase (PNP) deficiencyRasburicase (recombinant urate oxidase)Tumor lysis syndrome (TLS)Uricosuric agents (probenecid, sulfinpyrazone)
Blue pills sit on one specific arrow; grey ones are whole-pathway problems. Each opens the full condition card, which links back here with the arrow lit.
Facts worth knowing
Enzyme deficiency
- 4-month-old with a third pneumonia, no thymic shadow and critically low lymphocytes — ADA deficiency (SCID) (dATP inhibits ribonucleotide reductase → lymphocyte precursors arrest)
- Why humans get gout but most mammals don't — Humans lack urate oxidase (uricase) (Uric acid is far less soluble than allantoin)
- Deficiency of Adenosine deaminase (ADA) causes… — ADA deficiency → SCID (AR): adenosine/deoxyadenosine accumulate → dATP ↑ → ribonucleotide reductase inhibited → no dNTPs → T, B AND NK cells die; recurrent infections, no thymic shadow, fatal by ~2 y untreated; enzyme replacement, transplant, gene therapy (Lymphocytes have the highest ADA activity of any cell.)
- Deficiency of Purine nucleoside phosphorylase (PNP) causes… — PNP deficiency — milder, predominantly T-cell immunodeficiency (B cells relatively spared); supportive care / transplant
Diagnosis
- Gold-standard test to distinguish gout from pseudogout and septic arthritis — Needle-shaped, negatively birefringent monosodium urate crystals in synovial fluid under polarised light
Cause
- Share of hyperuricemia due to underexcretion vs overproduction — > 90% underexcretion; < 10% overproduction (Underexcretion: idiopathic renal defect, lactic acidosis, thiazides. Overproduction: PRPP synthetase gain of function, HFI, von Gierke, tumour lysis, Lesch-Nyhan)
Drug target
- Chronic gout drug for OVER-producers — Allopurinol (xanthine oxidase inhibitor) (Hypoxanthine and xanthine are excreted instead)
- Chronic gout drugs for UNDER-excretors — Uricosurics — probenecid, sulfinpyrazone (Goal: serum urate below ~6.5 mg/dL)
- Acute gout attack treatment — Colchicine, NSAIDs (indomethacin) or glucocorticoids (Target the inflammation, not the urate level)
- First-line urate-lowering agent in tumour lysis syndrome — Rasburicase (recombinant urate oxidase) (Degrades uric acid to soluble allantoin)
Compare
- Purine vs pyrimidine degradation end products — Purines → insoluble uric acid (crystal disease); pyrimidines → soluble β-alanine / β-aminoisobutyrate (no crystal disease)
Rate-limiting step
- Rate-limiting enzyme of purine degradation & uric acid — Xanthine oxidase (Uric acid is the final purine product in humans; serum saturation ≈ 6.5 mg/dL.)