Purine salvage and catabolism (to uric acid) — Lesch-Nyhan, ADA/PNP-SCID, xanthinuria

The cytosolic handling of purine bases and nucleosides after nucleic-acid/nucleotide turnover, comprising a salvage arm (which recycles free bases into nucleotides, sparing costly de novo synthesis) and a catabolic arm (which degrades purine nucleosides to the excretory end-product uric acid). Salvage: hypoxanthine-guanine phosphoribosyltransferase (HPRT1) transfers the phosphoribosyl group of PRPP onto hypoxanthine and guanine to regenerate IMP and GMP, and adenine phosphoribosyltransferase (APRT) does the same for adenine to regenerate AMP. Catabolism: adenosine deaminase (ADA) deaminates (deoxy)adenosine to (deoxy)inosine; purine nucleoside phosphorylase (PNP) phosphorolyses inosine, guanosine and their deoxy forms to the free bases hypoxanthine/guanine (which can then re-enter salvage via HPRT1 or continue to catabolism); and xanthine oxidoreductase (XDH) oxidises hypoxanthine to xanthine and xanthine to urate (uric acid), the final human purine catabolite (humans lack uricase). Inherited defects define classic disorders: HPRT1 deficiency causes Lesch-Nyhan syndrome (complete) or Kelley-Seegmiller gout/hyperuricemia (partial); APRT deficiency causes 2,8-dihydroxyadenine nephrolithiasis; ADA deficiency causes ADA-SCID and PNP deficiency a T-cell immunodeficiency (both from lymphotoxic deoxynucleotide accumulation); and XDH deficiency causes xanthinuria type I (XDH is the target of the gout drugs allopurinol/febuxostat).

MODULE:purine_salvage_and_catabolismDRAFTMetabolic Pathwaymodules/purine_salvage_and_catabolism.yaml
purine nucleobase metabolic processGO:0006144
GO:0006144
purine nucleobase metabolic process
The module is grounded in the GO purine nucleobase metabolic process (GO:0006144), spanning the salvage and catabolic arms.
Reactome:R-HSA-74259
Purine catabolism
Reaction stoichiometries follow the human Reactome purine salvage/catabolism reactions R-HSA-74215 (HPRT1), R-HSA-74213 (APRT), R-HSA-74241 (ADA), R-HSA-112033 (PNP) and R-HSA-74247 (XDH).
file:human/HPRT1/HPRT1-ai-review.yaml
HPRT1 gene review (human)
The hypoxanthine/guanine salvage step (UniProtKB:P00492, GO:0004422 + GO:0052657) matches the completed human HPRT1 review.
file:human/APRT/APRT-ai-review.yaml
APRT gene review (human)
The adenine salvage step (UniProtKB:P07741, GO:0003999) matches the completed human APRT review.
file:human/ADA/ADA-ai-review.yaml
ADA gene review (human)
The adenosine-deamination catabolic step (UniProtKB:P00813, GO:0004000) matches the completed human ADA review.
file:human/PNP/PNP-ai-review.yaml
PNP gene review (human)
The nucleoside-phosphorolysis step (UniProtKB:P00491, GO:0004731) matches the completed human PNP review.
file:human/XDH/XDH-ai-review.yaml
XDH gene review (human)
The terminal oxidation to urate (UniProtKB:P47989, GO:0004854 + GO:0004855) matches the completed human XDH review.
6Nodes
5Parts
0Variant Sets
0Variants
5Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:purine_salvage_and_catabolism deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (5/5 grounded genes reviewed)

5 complete review(s) · 0 with deep research · 0 missing review · 5 reviewed but lacking deep research

Gene Review Complete Deep research
ADA P00813 ✓ ✓ ✗
APRT P07741 ✓ ✓ ✗
HPRT1 P00492 ✓ ✓ ✗
PNP P00491 ✓ ✓ ✗
XDH P47989 ✓ ✓ ✗

Details

Context
cytosolGO:0005829
Purine salvage and catabolismMetabolic Pathwaypurine_salvage_and_catabolism
purine nucleobase metabolic processGO:0006144
Context
cytosolGO:0005829

Purine base salvage (HPRT1, APRT) and nucleoside catabolism to uric acid (ADA -> PNP -> XDH) grounded to the human enzymes HPRT1 (UniProtKB:P00492, GO:0004422 / GO:0052657, EC 2.4.2.8), APRT (P07741, GO:0003999, EC 2.4.2.7), ADA (P00813, GO:0004000, EC 3.5.4.4), PNP (P00491, GO:0004731, EC 2.4.2.1) and XDH (P47989, GO:0004854 / GO:0004855, EC 1.17.1.4 / 1.17.3.2). GO molecular-function terms were taken from the human GOA records; Reactome reaction ids and titles were verified against the local reactome cache. Each step uses a PANTHER family selector (generic over paralogs and orthologs) plus a concrete human representative member. PNP is the branch point: the hypoxanthine/guanine it releases is either salvaged (HPRT1) or oxidised to urate (XDH). De novo purine synthesis and the purine nucleotide cycle (e.g. ADSL, AMPD) are out of scope for this salvage/catabolism module; ecto-ADA/CD26 signalling is captured non-core in the ADA gene review.

Connections

ada_step -> pnp_step Provides Input For
(Deoxy)inosine from ADA is phosphorolysed by PNP.
pnp_step -> xdh_step Provides Input For
Hypoxanthine released by PNP is oxidised to xanthine/urate by XDH.
pnp_step -> hprt1_step Provides Input For
Hypoxanthine/guanine released by PNP can instead be salvaged back to IMP/GMP by HPRT1 (the salvage-vs-catabolism branch point).
Part 1: salvage of hypoxanthine and guanine
hypoxanthine/guanine + PRPP to IMP/GMP + PPiReactionhprt1_step

Annotons

HPRT1: hypoxanthine-guanine phosphoribosyltransferase
hprt1_activity
Participant: Family: Hypoxanthine-guanine phosphoribosyltransferase family (HPRT1)
Family:
Hypoxanthine-guanine phosphoribosyltransferase family (HPRT1)PANTHER:PTHR43340
Representative Members: HPRT1 (human)UniProtKB:P00492

Function

hypoxanthine phosphoribosyltransferase activityGO:0004422
Substrates: hypoxanthine / guanine 5-phospho-alpha-D-ribose 1-diphosphate (PRPP)
Products: IMP / GMP diphosphate

Locations

cytosolGO:0005829

Salvages hypoxanthine and guanine to IMP and GMP (also carries guanine PRT activity, GO:0052657). Complete deficiency causes Lesch-Nyhan syndrome; partial deficiency causes gout/hyperuricemia (Kelley-Seegmiller).

Part 2: salvage of adenine
adenine + PRPP to AMP + PPiReactionaprt_step

Annotons

APRT: adenine phosphoribosyltransferase
aprt_activity
Participant: Family: Adenine phosphoribosyltransferase family (APRT)
Family:
Adenine phosphoribosyltransferase family (APRT)PANTHER:PTHR32315
Representative Members: APRT (human)UniProtKB:P07741

Function

adenine phosphoribosyltransferase activityGO:0003999
Substrates: adenine PRPP
Products: AMP diphosphate

Locations

cytosolGO:0005829

Salvages adenine to AMP. Deficiency diverts adenine to XDH-mediated oxidation, forming insoluble 2,8-dihydroxyadenine (2,8-DHA nephrolithiasis).

Part 3: catabolism — adenosine deamination
(deoxy)adenosine to (deoxy)inosine + NH3Reactionada_step

Annotons

ADA: adenosine deaminase
ada_activity
Participant: Family: Adenosine/AMP deaminase family (ADA)
Family:
Adenosine/AMP deaminase family (ADA)PANTHER:PTHR11409
Representative Members: ADA (human)UniProtKB:P00813

Function

adenosine deaminase activityGO:0004000
Substrates: adenosine / 2'-deoxyadenosine water
Products: inosine / 2'-deoxyinosine ammonia

Locations

cytosolGO:0005829

Zinc metalloenzyme deaminating (deoxy)adenosine; essential in lymphocytes (deficiency -> toxic dATP -> ADA-SCID). Also acts as ecto-ADA at the cell surface with CD26/DPP4 (non-core role).

Part 4: catabolism — nucleoside phosphorolysis (feeds salvage or catabolism)
inosine/guanosine + Pi to hypoxanthine/guanine + (deoxy)ribose-1-phosphateReactionpnp_step

Annotons

PNP: purine nucleoside phosphorylase
pnp_activity
Participant: Family: Purine nucleoside phosphorylase / MTAP family (PNP)
Family:
Purine nucleoside phosphorylase / MTAP family (PNP)PANTHER:PTHR11904
Representative Members: PNP (human)UniProtKB:P00491

Function

purine-nucleoside phosphorylase activityGO:0004731
Substrates: inosine / guanosine / 2'-deoxy forms phosphate
Products: hypoxanthine / guanine (deoxy)ribose-1-phosphate

Locations

cytosolGO:0005829

Homotrimeric phosphorylase releasing hypoxanthine/guanine (which can be salvaged by HPRT1 or catabolised by XDH). Specific for 6-oxopurine nucleosides (not adenosine). Deficiency causes a T-cell immunodeficiency (toxic dGTP).

Part 5: terminal oxidation to uric acid
hypoxanthine to xanthine to urateReactionxdh_step

Annotons

XDH: xanthine oxidoreductase
xdh_activity
Participant: Family: Xanthine dehydrogenase/oxidase (molybdo-flavoenzyme) family (XDH)
Family:
Xanthine dehydrogenase/oxidase (molybdo-flavoenzyme) family (XDH)PANTHER:PTHR45444
Representative Members: XDH (human)UniProtKB:P47989

Function

xanthine dehydrogenase activityGO:0004854
Substrates: hypoxanthine / xanthine NAD+ (dehydrogenase form) or O2 (oxidase form)
Products: xanthine / urate NADH or H2O2/superoxide

Locations

cytosolGO:0005829

Molybdopterin/FAD/Fe-S oxidoreductase carrying out the last two purine- catabolic steps (hypoxanthine -> xanthine -> urate, the terminal human catabolite; humans lack uricase). Interconverts between an NAD+-linked dehydrogenase (XDH) and an O2-linked, ROS-generating oxidase (XO) form. Deficiency causes xanthinuria type I; the drug target of allopurinol.