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.

Pathway

Purine degradation & uric acid · Cytosol (nucleotidase, PNP, ADA) and liver/gut xanthine oxidase; uric acid excreted by the kidney. Enzymes sit beside the arrows, ★ = rate-limiting, ⊕/⊖ = activators/inhibitors (toggle), −ATP +NADH = what the step spends and makes (toggle ⚡), dashed = allosteric signal, shaded bands = compartment. Drag to pan.

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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 — SCID Allopurinol Gout Hyperuricemia — underexcretion (primary and secondary)Pseudogout (CPPD deposition)Purine nucleoside phosphorylase (PNP) deficiency Rasburicase (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.)