Purine base and nucleoside salvage, with oxidation of purine bases to urate

The cytosolic handling of purine bases and nucleosides released by nucleic-acid and nucleotide turnover or taken up from outside the cell. A salvage arm recycles them into nucleotides, sparing costly de novo synthesis: phosphoribosyltransferases transfer the phosphoribosyl group of PRPP to adenine (adenine phosphoribosyltransferase, giving AMP), to hypoxanthine and guanine (hypoxanthine-guanine phosphoribosyltransferase, giving IMP and GMP) and, in fungi and bacteria, to xanthine (xanthine phosphoribosyltransferase, giving XMP); adenosine kinase phosphorylates adenosine to AMP. Interconverting deaminations and phosphorolysis route bases between these entry points: adenosine deaminase (animals) or adenine deaminase (fungi, bacteria) converts the adenine moiety to the hypoxanthine level, purine nucleoside phosphorylase releases hypoxanthine and guanine from inosine and guanosine, and guanine deaminase converts guanine to xanthine. An optional catabolic arm oxidises hypoxanthine and xanthine to urate, by molybdenum-dependent xanthine oxidoreductase in animals, plants and many bacteria, or, for xanthine, by an alpha-ketoglutarate-dependent xanthine dioxygenase found only in fungi. Some organisms lack the catabolic arm entirely: budding yeast has no xanthine oxidoreductase, xanthine dioxygenase or urate oxidase and only salvages purine bases. In humans, inherited defects define classic disorders: complete HPRT1 deficiency causes Lesch-Nyhan syndrome and partial deficiency gout/hyperuricemia; APRT deficiency causes 2,8-dihydroxyadenine nephrolithiasis; ADA and PNP deficiencies cause immunodeficiency through lymphotoxic deoxynucleotide accumulation; and XDH deficiency causes xanthinuria type I (XDH is the target of allopurinol and febuxostat).

MODULE:purine_salvage_and_catabolismDRAFTMetabolic Pathwaymodules/purine_salvage_and_catabolism.yaml
purine-containing compound salvageGO:0043101 purine nucleobase metabolic processGO:0006144
YeastPathways:PWY3O-1
salvage pathways of purines and their nucleosides (S. cerevisiae, SGD YeastPathways)
APT1/APT2, HPT1, XPT1, AAH1, ADO1, GUD1, PNP1 and AMD1. APT2 is a pseudogene with no APRT activity (PMID:9864350); AMD1 AMP deaminase is modelled in purine_nucleotide_interconversion.
YeastPathways:PWY3O-2220
salvage pathways of adenine, hypoxanthine and their nucleosides (S. cerevisiae, SGD YeastPathways)
Adenine/hypoxanthine subset of PWY3O-1 (APT1/APT2, HPT1, AAH1, ADO1, PNP1, AMD1).
YeastPathways:PWY3O-743
salvage pathways of guanine, xanthine and their nucleosides (S. cerevisiae, SGD YeastPathways)
Guanine/xanthine subset (HPT1, GUD1, XPT1).
YeastPathways:PWY3O-285
superpathway of purine biosynthesis and salvage pathways (S. cerevisiae, SGD YeastPathways)
Union of de novo IMP synthesis, interconversion, ribonucleotide reduction and salvage; also includes the IMP 5'-nucleotidase ISN1, which belongs to purine nucleotide catabolism.
GO:0043101
purine-containing compound salvage
Module-level process term for the salvage arm.
GO:0006144
purine nucleobase metabolic process
Broader process term spanning salvage and the oxidative catabolic arm.
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).
PMID:9864350
APT1, but not APT2, codes for a functional adenine phosphoribosyltransferase in Saccharomyces cerevisiae.
APT1 encodes the functional yeast APRT; APT2 is a non-expressed, inactive duplicate (pseudogene).
PMID:6392474
Adenine phosphoribosyltransferase mutants in Saccharomyces cerevisiae.
Genetic identification of yeast APRT mutants.
PMID:6355764
Hypoxanthine: guanine phosphoribosyltransferase mutants in Saccharomyces cerevisiae.
hpt1 mutants lacking HGPRT activity are 8-azaguanine resistant and excrete purines.
PMID:18245832
Lethal accumulation of guanylic nucleotides in Saccharomyces cerevisiae HPT1-deregulated mutants.
Yeast HGPRT is feedback-inhibited by GMP; feedback-insensitive mutants accumulate toxic guanylic nucleotides on guanine.
PMID:10217799
Isolation and characterization of the Saccharomyces cerevisiae XPT1 gene encoding xanthine phosphoribosyl transferase.
XPT1 encodes yeast XPRT; its disruption impairs xanthine utilisation without affecting HPRT.
PMID:11223943
Role of adenosine kinase in Saccharomyces cerevisiae: identification of the ADO1 gene and study of the mutant phenotypes.
ADO1 encodes adenosine kinase, recycling adenosine produced by the methyl cycle.
PMID:1577682
Adenine deaminase and adenine utilization in Saccharomyces cerevisiae.
Exogenous adenine is used through either adenine deaminase (AAH) or APRT; exogenous adenosine cannot normally be used as a purine source.
PMID:11466296
YLR209c encodes Saccharomyces cerevisiae purine nucleoside phosphorylase.
PNP1 acts on inosine and guanosine; pnp1 mutants excrete these nucleosides.
PMID:15565584
GUD1 (YDL238c) encodes Saccharomyces cerevisiae guanine deaminase, an enzyme expressed during post-diauxic growth.
GUD1 encodes guanine deaminase producing xanthine and ammonia.
PMID:15948966
Convergent evolution of hydroxylation mechanisms in the fungal kingdom: molybdenum cofactor-independent hydroxylation of xanthine via alpha-ketoglutarate-dependent dioxygenases.
Fungi have, besides xanthine dehydrogenase, an alpha-ketoglutarate- and Fe(II)-dependent xanthine dioxygenase (A. nidulans XanA); inactivating the S. pombe homologue impairs xanthine use as nitrogen source.
PMID:23670538
Nucleotide degradation and ribose salvage in yeast.
Pnp1 and the pyrimidine nucleoside hydrolase Urh1 release ribose from nucleosides during starvation, feeding the pentose phosphate pathway.
PMID:17052198
Regulation of purine nucleotide biosynthesis: in yeast and beyond.
Review of de novo and salvage balance of adenine and guanine nucleotide pools in yeast.
PMID:22419079
Regulation of amino acid, nucleotide, and phosphate metabolism in Saccharomyces cerevisiae.
YeastBook review of purine salvage and its regulation.
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.
13Nodes
8Parts
2Variant Sets
4Variants
11Annotons
7Connections

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.

Function consistency and core coverage

21 gene-function check(s) reflected in core functions · 0 conflict(s) · 4 evidence or coverage gap(s) (44 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
aprt_activity APRT (human)
UniProtKB:P07741
Family Representative 		adenine phosphoribosyltransferase activity
GO:0003999 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aprt_activity APT1 (Saccharomyces cerevisiae)
UniProtKB:P49435
Family Representative 		adenine phosphoribosyltransferase activity
GO:0003999 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aprt_activity apt1 (Schizosaccharomyces pombe)
UniProtKB:O42842
Family Representative 		adenine phosphoribosyltransferase activity
GO:0003999 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hprt1_activity HPRT1 (human)
UniProtKB:P00492
Family Representative 		hypoxanthine phosphoribosyltransferase activity
GO:0004422 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hprt1_activity HPT1 (Saccharomyces cerevisiae)
UniProtKB:Q04178
Family Representative 		hypoxanthine phosphoribosyltransferase activity
GO:0004422 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hprt1_activity hpt1 (Schizosaccharomyces pombe)
UniProtKB:O13917
Family Representative 		hypoxanthine phosphoribosyltransferase activity
GO:0004422 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hprt1_activity hpt (Escherichia coli K-12)
UniProtKB:P0A9M2
Family Representative 		hypoxanthine phosphoribosyltransferase activity
GO:0004422 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
guanine_prt_activity HPRT1 (human)
UniProtKB:P00492
Family Representative 		guanine phosphoribosyltransferase activity
GO:0052657 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
guanine_prt_activity HPT1 (Saccharomyces cerevisiae)
UniProtKB:Q04178
Family Representative 		guanine phosphoribosyltransferase activity
GO:0052657 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
guanine_prt_activity hpt1 (Schizosaccharomyces pombe)
UniProtKB:O13917
Family Representative 		guanine phosphoribosyltransferase activity
GO:0052657 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
xprt_activity XPT1 (Saccharomyces cerevisiae)
UniProtKB:P47165
Family Representative 		xanthine phosphoribosyltransferase activity
GO:0000310 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
xprt_activity gpt (Escherichia coli K-12)
UniProtKB:P0A9M5
Family Representative 		xanthine phosphoribosyltransferase activity
GO:0000310 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
adenosine_kinase_activity ADO1 (Saccharomyces cerevisiae)
UniProtKB:P47143
Family Representative 		adenosine kinase activity
GO:0004001 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adenosine_kinase_activity ADK (human)
UniProtKB:P55263
Family Representative 		adenosine kinase activity
GO:0004001 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
adenine_deaminase_activity AAH1 (Saccharomyces cerevisiae)
UniProtKB:P53909
Family Representative 		adenine deaminase activity
GO:0000034 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
adenine_deaminase_activity dea2 (Schizosaccharomyces pombe)
UniProtKB:Q9P6I7
Family Representative 		adenine deaminase activity
GO:0000034 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ada_activity ADA (human)
UniProtKB:P00813
Family Representative 		adenosine deaminase activity
GO:0004000 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pnp_activity PNP (human)
UniProtKB:P00491
Family Representative 		purine-nucleoside phosphorylase activity
GO:0004731 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pnp_activity PNP1 (Saccharomyces cerevisiae)
UniProtKB:Q05788
Family Representative 		purine-nucleoside phosphorylase activity
GO:0004731 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
guanine_deaminase_activity GUD1 (Saccharomyces cerevisiae)
UniProtKB:Q07729
Family Representative 		guanine deaminase activity
GO:0008892 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
guanine_deaminase_activity gud1 (Schizosaccharomyces pombe)
UniProtKB:O14057
Family Representative 		guanine deaminase activity
GO:0008892 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
guanine_deaminase_activity GDA (human)
UniProtKB:Q9Y2T3
Family Representative 		guanine deaminase activity
GO:0008892 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
xdh_activity XDH (human)
UniProtKB:P47989
Family Representative 		xanthine dehydrogenase activity
GO:0004854 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
xanthine_dioxygenase_activity xan1 (Schizosaccharomyces pombe)
UniProtKB:O74885
Family Representative 		alpha-ketoglutarate-dependent xanthine dioxygenase activity
GO:0097641 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aprt_activity Adenine phosphoribosyltransferase family (APRT/Apt)
PANTHER:PTHR32315:SF3
Family 		adenine phosphoribosyltransferase activity
GO:0003999 		Family Supported
Family review supports GO:0003999 for PANTHER:PTHR32315:SF3. APRT (SF3); purine_salvage_and_catabolism selects the base family, which also takes in Upp.
hprt1_activity Hypoxanthine-guanine phosphoribosyltransferases
PANTHER:PTHR43340:SF6
Family 		hypoxanthine phosphoribosyltransferase activity
GO:0004422 		Family Supported
Family review supports GO:0004422 for PANTHER:PTHR43340:SF6. Asserted by purine_salvage_and_catabolism; accepted by HPRT1.
hprt1_activity Hypoxanthine-guanine phosphoribosyltransferases
PANTHER:PTHR43340:SF11
Family 		hypoxanthine phosphoribosyltransferase activity
GO:0004422 		Family Supported
Family review supports GO:0004422 for PANTHER:PTHR43340:SF11. Asserted by purine_salvage_and_catabolism; accepted by HPRT1.
hprt1_activity Hypoxanthine-guanine phosphoribosyltransferases
PANTHER:PTHR43340:SF1
Family 		hypoxanthine phosphoribosyltransferase activity
GO:0004422 		Family Supported
Family review supports GO:0004422 for PANTHER:PTHR43340:SF1. Asserted by purine_salvage_and_catabolism; accepted by HPRT1.
hprt1_activity Hypoxanthine-guanine phosphoribosyltransferases
PANTHER:PTHR43363:SF1
Family 		hypoxanthine phosphoribosyltransferase activity
GO:0004422 		Family Supported
Family review supports GO:0004422 for PANTHER:PTHR43363:SF1. HGPRT in SF1, as purine_salvage_and_catabolism selects; accepted by HPT1 and hpt1. XPT1 (SF4) keeps a low, ancestral HPRT activity, seen when overexpressed.
guanine_prt_activity Hypoxanthine-guanine phosphoribosyltransferases
PANTHER:PTHR43340:SF6
Family 		guanine phosphoribosyltransferase activity
GO:0052657 		Family Supported
Family review supports GO:0052657 for PANTHER:PTHR43340:SF6. Guanine phosphoribosyltransferase for HGPRT (HPRT1), as purine_salvage_and_catabolism selects.
guanine_prt_activity Hypoxanthine-guanine phosphoribosyltransferases
PANTHER:PTHR43340:SF11
Family 		guanine phosphoribosyltransferase activity
GO:0052657 		Family Supported
Family review supports GO:0052657 for PANTHER:PTHR43340:SF11. Guanine phosphoribosyltransferase for HGPRT (HPRT1), as purine_salvage_and_catabolism selects.
guanine_prt_activity Hypoxanthine-guanine phosphoribosyltransferases
PANTHER:PTHR43363:SF1
Family 		guanine phosphoribosyltransferase activity
GO:0052657 		Family Supported
Family review supports GO:0052657 for PANTHER:PTHR43363:SF1. Fungal HGPRT (SF1: S. cerevisiae HPT1, S. pombe hpt1), as purine_salvage_and_catabolism selects.
xprt_activity xanthine phosphoribosyltransferases (fungal Xpt1 and bacterial Gpt types)
PANTHER:PTHR43363:SF4
Family 		xanthine phosphoribosyltransferase activity
GO:0000310 		Family Supported
Family review supports GO:0000310 for PANTHER:PTHR43363:SF4. Xanthine phosphoribosyltransferase for XPT1 (SF4) and for S. pombe hpt1 (SF1), where one enzyme carries all three base activities. S. cerevisiae HPT1 does not use xanthine.
xprt_activity xanthine phosphoribosyltransferases (fungal Xpt1 and bacterial Gpt types)
PANTHER:PTHR39563
Family 		xanthine phosphoribosyltransferase activity
GO:0000310 		Family Supported
Family review supports GO:0000310 FAMILY_WIDE. The defining Gpt activity; no member gene review exists.
adenosine_kinase_activity adenosine kinases
PANTHER:PTHR45769
Family 		adenosine kinase activity
GO:0004001 		Family Supported
Family review supports GO:0004001 FAMILY_WIDE. Asserted by purine_salvage_and_catabolism; accepted by ADO1.
adenine_deaminase_activity fungal adenine deaminases (adenosine deaminase fold)
PANTHER:PTHR43114:SF6
Family 		adenine deaminase activity
GO:0000034 		Family Supported
Family review supports GO:0000034 for PANTHER:PTHR43114:SF6. Asserted by purine_salvage_and_catabolism; accepted by AAH1 and dea2 in SF6.
ada_activity Adenosine/AMP deaminase family (ADA)
PANTHER:PTHR11409:SF43
Family 		adenosine deaminase activity
GO:0004000 		Family Supported
Family review supports GO:0004000 for PANTHER:PTHR11409:SF43. ADA and ADA2 subfamilies; both modules select the base family, which also takes in ADAL/MAPDA.
ada_activity Adenosine/AMP deaminase family (ADA)
PANTHER:PTHR11409:SF49
Family 		adenosine deaminase activity
GO:0004000 		Family Supported
Family review supports GO:0004000 for PANTHER:PTHR11409:SF49. ADA and ADA2 subfamilies; both modules select the base family, which also takes in ADAL/MAPDA.
ada_activity Adenosine/AMP deaminase family (ADA)
PANTHER:PTHR11409:SF39
Family 		adenosine deaminase activity
GO:0004000 		Family Supported
Family review supports GO:0004000 for PANTHER:PTHR11409:SF39. ADA and ADA2 subfamilies; both modules select the base family, which also takes in ADAL/MAPDA.
ada_activity Adenosine/AMP deaminase family (ADA)
PANTHER:PTHR11409:SF45
Family 		adenosine deaminase activity
GO:0004000 		Family Supported
Family review supports GO:0004000 for PANTHER:PTHR11409:SF45. ADA and ADA2 subfamilies; both modules select the base family, which also takes in ADAL/MAPDA.
pnp_activity Purine nucleoside phosphorylase / MTAP family (PNP)
PANTHER:PTHR11904
Family 		purine-nucleoside phosphorylase activity
GO:0004731 		Family Supported
Family review supports GO:0004731 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal, purine_nucleotide_catabolism and purine_salvage_and_catabolism; accepted by PNP1, SPAC1805.16c and PNP.
guanine_deaminase_activity guanine deaminases
PANTHER:PTHR11271:SF6
Family 		guanine deaminase activity
GO:0008892 		Family Supported
Family review supports GO:0008892 for PANTHER:PTHR11271:SF6. SF6, as bacterial_purine_base_oxidation_to_urate and purine_salvage_and_catabolism select; purine_nucleotide_catabolism uses the base family, which also takes in HutF.
xdh_activity Xanthine dehydrogenase/oxidase (molybdo-flavoenzyme) family (XDH)
Family 		xanthine dehydrogenase activity
GO:0004854 		Family Id Missing
The family has no identifier linking it to a curated family review.
xanthine_dioxygenase_activity fungal alpha-ketoglutarate-dependent xanthine dioxygenases
PANTHER:PTHR43779:SF2
Family 		alpha-ketoglutarate-dependent xanthine dioxygenase activity
GO:0097641 		Family Supported
Family review supports GO:0097641 for PANTHER:PTHR43779:SF2. Asserted by purine_salvage_and_catabolism; accepted by xan1.

Gene-review completeness (18/21 grounded genes reviewed)

17 complete review(s) · 7 with deep research · 3 missing review · 11 reviewed but lacking deep research

Gene Review Complete Deep research
AAH1 P53909 ✓ ✓ ✓
ADA P00813 ✓ 66/69 ✗
ADO1 P47143 ✓ ✓ ✓
APRT P07741 ✓ ✓ ✗
apt1 O42842 ✓ ✓ ✗
APT1 P49435 ✓ ✓ ✓
dea2 Q9P6I7 ✓ ✓ ✗
GDA Q9Y2T3 ✓ ✓ ✗
GUD1 Q07729 ✓ ✓ ✓
HPRT1 P00492 ✓ ✓ ✗
hpt1 O13917 ✓ ✓ ✗
HPT1 Q04178 ✓ ✓ ✓
hpt (Escherichia coli K-12) P0A9M2 ✗ — —
gpt (Escherichia coli K-12) P0A9M5 ✗ — —
ADK (human) P55263 ✗ — —
PNP P00491 ✓ ✓ ✗
PNP1 Q05788 ✓ ✓ ✓
SPCC1672.03c O14057 ✓ ✓ ✗
xan1 O74885 ✓ ✓ ✗
XDH P47989 ✓ ✓ ✗
XPT1 P47165 ✓ ✓ ✓

Details

Context
cytosolGO:0005829
Purine base and nucleoside salvage and oxidation to urateMetabolic Pathwaypurine_salvage_and_catabolism
purine-containing compound salvageGO:0043101 purine nucleobase metabolic processGO:0006144
Context
cytosolGO:0005829

GENERALIZE from the earlier human-only module (HPRT1 P00492, APRT P07741, ADA P00813, PNP P00491, XDH P47989; GO terms from human GOA; Reactome reactions verified against the local cache), now species-neutral with fungal exemplars from the YeastPathways crosswalk (PWY3O-1, PWY3O-2220, PWY3O-743, PWY3O-285) and the PomBase model 680ad14200001682. Added parts: XPRT (optional; fungi and bacteria; XPT1), adenosine kinase (ADO1), an adenine-moiety deamination variant set (fungal/bacterial adenine deaminase AAH1/dea2 versus animal adenosine deaminase ADA; neither S. cerevisiae nor S. pombe encodes adenosine deaminase), guanine deaminase (GUD1/gud1/GDA) and a separate guanine PRTase annoton for HGPRT. The oxidation to urate is now optional with two enzyme variants (XDH and the fungal Xan1/XanA dioxygenase) because S. cerevisiae has neither: its realisation of this module is salvage-only (no S288C protein in UniProt carries EC 1.17.1.4, 1.17.3.2, 1.14.11.48 or 1.7.3.3; checked 2026-10-06), whereas S. pombe oxidises xanthine with xan1 but has no xanthine dehydrogenase. YeastCyc corrections: APT2 is listed as an APRT in PWY3O-1/PWY3O-2220 but is a pseudogene without activity (PMID:9864350) and is not used as an exemplar; AMD1 AMP deaminase is placed in the salvage frames but is modelled in purine_nucleotide_interconversion; ISN1 IMP 5'-nucleotidase (PWY3O-285) belongs to purine_nucleotide_catabolism; the superpathway's de novo, interconversion and RNR reactions belong to de_novo_purine_synthesis, purine_nucleotide_interconversion and dntp_de_novo_synthesis. GO-CAM disagreements: YeastPathways uses GO:0004422 for both the hypoxanthine and guanine HPT1 reactions (the guanine reaction is GO:0052657) and lists APT2 as an enabler; the PomBase model gives S. pombe hpt1 xanthine PRTase activity, and assigns adenine deaminase activity also to SPBC1683.02 (UniProt Q9P6J8, an uncharacterised PTHR43114:SF7 deaminase), which is not used as an exemplar here. PomBase also models plasma-membrane nucleobase transporters and urate oxidase (uro1), which are outside the enzymatic core (uptake; ureide catabolism). Nucleotide-level catabolism (5'-nucleotidases, AMP deaminase) is in purine_nucleotide_catabolism and purine_nucleotide_interconversion; ecto-ADA/CD26 signalling is captured non-core in the ADA gene review.

Connections

adenine_moiety_deamination -> pnp_step Provides Input For
(Deoxy)inosine from adenosine deaminase is phosphorolysed by PNP.
adenine_moiety_deamination -> hprt1_step Provides Input For
Hypoxanthine from adenine deaminase is salvaged to IMP by HGPRT.
pnp_step -> hprt1_step Provides Input For
Hypoxanthine/guanine released by PNP can be salvaged back to IMP/GMP by HGPRT (the salvage-vs-catabolism branch point).
pnp_step -> guanine_deamination_step Provides Input For
Guanine released by PNP can be deaminated to xanthine.
guanine_deamination_step -> xprt_step Provides Input For
Xanthine is salvaged to XMP where XPRT exists.
pnp_step -> purine_base_oxidation Provides Input For
Hypoxanthine released by PNP is oxidised to xanthine/urate by XDH where present.
Xanthine is oxidised to urate by XDH or Xan1 where present.
Part 1: salvage of adenine
adenine + PRPP to AMP + PPiReactionaprt_step

Annotons

Adenine phosphoribosyltransferase
aprt_activity
Participant: Family: Adenine phosphoribosyltransferase family (APRT/Apt)
Family:
Adenine phosphoribosyltransferase family (APRT/Apt)
Representative Members: APRT (human)UniProtKB:P07741 APT1 (Saccharomyces cerevisiae)UniProtKB:P49435 apt1 (Schizosaccharomyces pombe)UniProtKB:O42842

Function

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

Locations

cytosolGO:0005829

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

Part 2: salvage of hypoxanthine and guanine
hypoxanthine/guanine + PRPP to IMP/GMP + PPiReactionhprt1_step

Annotons

Hypoxanthine phosphoribosyltransferase (HGPRT)
hprt1_activity
Participant: Family: Hypoxanthine-guanine phosphoribosyltransferases
Family:
Hypoxanthine-guanine phosphoribosyltransferases
Representative Members: HPRT1 (human)UniProtKB:P00492 HPT1 (Saccharomyces cerevisiae)UniProtKB:Q04178 hpt1 (Schizosaccharomyces pombe)UniProtKB:O13917 hpt (Escherichia coli K-12)UniProtKB:P0A9M2

Function

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

Locations

cytosolGO:0005829

Salvages hypoxanthine to IMP. Complete human HPRT1 deficiency causes Lesch-Nyhan syndrome; partial deficiency causes gout/hyperuricemia (Kelley-Seegmiller).

Guanine phosphoribosyltransferase (HGPRT)
guanine_prt_activity
Participant: Family: Hypoxanthine-guanine phosphoribosyltransferases
Family:
Hypoxanthine-guanine phosphoribosyltransferases
Representative Members: HPRT1 (human)UniProtKB:P00492 HPT1 (Saccharomyces cerevisiae)UniProtKB:Q04178 hpt1 (Schizosaccharomyces pombe)UniProtKB:O13917

Function

guanine phosphoribosyltransferase activityGO:0052657
Substrates: guanine PRPP
Products: GMP diphosphate

Salvages guanine to GMP. The yeast enzyme is feedback-inhibited by GMP, and deregulated mutants accumulate toxic guanylic nucleotides (PMID:18245832).

Part 3: salvage of xanthine (fungi and bacteria) (optional)
xanthine + PRPP to XMP + PPiReactionxprt_step

Annotons

Xanthine phosphoribosyltransferase
xprt_activity
Participant: Family: xanthine phosphoribosyltransferases (fungal Xpt1 and bacterial Gpt types)
Family:
xanthine phosphoribosyltransferases (fungal Xpt1 and bacterial Gpt types)
Representative Members: XPT1 (Saccharomyces cerevisiae)UniProtKB:P47165 gpt (Escherichia coli K-12)UniProtKB:P0A9M5

Function

xanthine phosphoribosyltransferase activityGO:0000310
Substrates: xanthine PRPP
Products: XMP diphosphate

Returns xanthine (from guanine deamination) to the nucleotide pool as XMP, which GMP synthase converts to GMP. Mammals lack a dedicated XPRT, so the step is optional.

Part 4: adenosine phosphorylation
adenosine + ATP to AMP + ADPReactionadenosine_kinase_step

Annotons

Adenosine kinase
adenosine_kinase_activity
Participant: Family: adenosine kinases
Family:
adenosine kinasesPANTHER:PTHR45769
Representative Members: ADO1 (Saccharomyces cerevisiae)UniProtKB:P47143 ADK (human)UniProtKB:P55263

Function

adenosine kinase activityGO:0004001
Substrates: adenosine ATP
Products: AMP ADP

Recycles adenosine released by S-adenosylhomocysteine hydrolysis (methyl cycle) to AMP.

Part 5: deamination of the adenine moiety to the hypoxanthine level
Adenine or adenosine deaminationReactionadenine_moiety_deamination
Variant set: Substrate of adenine-moiety deamination by base (adenine deaminase) versus nucleoside (adenosine deaminase) (One Or More)
Adenine deaminase (fungi, bacteria)Reactionadenine_deaminase_route

Annotons

Adenine deaminase
adenine_deaminase_activity
Participant: Family: fungal adenine deaminases (adenosine deaminase fold)
Family:
fungal adenine deaminases (adenosine deaminase fold)PANTHER:PTHR43114:SF6
Representative Members: AAH1 (Saccharomyces cerevisiae)UniProtKB:P53909 dea2 (Schizosaccharomyces pombe)UniProtKB:Q9P6I7

Function

adenine deaminase activityGO:0000034
Substrates: adenine water
Products: hypoxanthine ammonia

Converts adenine to hypoxanthine, which HGPRT salvages to IMP; with APRT this is one of the two entry routes for exogenous adenine in yeast, and Aah1 also supplies nitrogen (PMID:1577682).

Adenosine deaminase (animals, many bacteria)Reactionadenosine_deaminase_route

Annotons

Adenosine deaminase
ada_activity
Participant: Family: Adenosine/AMP deaminase family (ADA)
Family:
Adenosine/AMP deaminase family (ADA)
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). Absent from S. cerevisiae and S. pombe, which deaminate the free base instead.

Part 6: nucleoside phosphorolysis (feeds salvage or catabolism)
inosine/guanosine + Pi to hypoxanthine/guanine + (deoxy)ribose-1-phosphateReactionpnp_step

Annotons

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 PNP1 (Saccharomyces cerevisiae)UniProtKB:Q05788

Function

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

Locations

cytosolGO:0005829

Releases hypoxanthine/guanine (salvaged by HGPRT or, where the catabolic arm exists, oxidised) and ribose 1-phosphate, whose carbon is recycled through the pentose phosphate pathway during starvation (PMID:23670538). Specific for 6-oxopurine nucleosides (not adenosine). Human deficiency causes a T-cell immunodeficiency (toxic dGTP).

Part 7: guanine deamination
guanine + H2O to xanthine + NH3Reactionguanine_deamination_step

Annotons

Guanine deaminase
guanine_deaminase_activity
Participant: Family: guanine deaminases
Family:
guanine deaminasesPANTHER:PTHR11271:SF6
Representative Members: GUD1 (Saccharomyces cerevisiae)UniProtKB:Q07729 gud1 (Schizosaccharomyces pombe)UniProtKB:O14057 GDA (human)UniProtKB:Q9Y2T3

Function

guanine deaminase activityGO:0008892
Substrates: guanine water
Products: xanthine ammonia

Converts guanine to xanthine, which is either salvaged by XPRT (fungi, bacteria) or oxidised to urate.

Part 8: oxidation of purine bases to urate (optional)
hypoxanthine to xanthine to urateReactionpurine_base_oxidation

Absent from Saccharomyces cerevisiae, which encodes no xanthine oxidoreductase, xanthine dioxygenase or urate oxidase.

Variant set: Xanthine-oxidising enzyme by enzyme chemistry (molybdenum hydroxylase versus Fe(II)/alpha-ketoglutarate dioxygenase) (One Or More)

Fungi such as Aspergillus nidulans have both xanthine dehydrogenase and XanA (PMID:15948966).

Molybdenum xanthine oxidoreductase (XDH/XO)Reactionxdh_variant

Annotons

XDH: xanthine oxidoreductase
xdh_activity
Participant: Family: Xanthine dehydrogenase/oxidase (molybdo-flavoenzyme) family (XDH)
Family:
Xanthine dehydrogenase/oxidase (molybdo-flavoenzyme) family (XDH)
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.

Alpha-ketoglutarate-dependent xanthine dioxygenase (fungal XanA/Xan1)Reactionxan1_dioxygenase_variant

Annotons

Xanthine dioxygenase (Xan1/XanA)
xanthine_dioxygenase_activity
Participant: Family: fungal alpha-ketoglutarate-dependent xanthine dioxygenases
Family:
fungal alpha-ketoglutarate-dependent xanthine dioxygenasesPANTHER:PTHR43779:SF2
Representative Members: xan1 (Schizosaccharomyces pombe)UniProtKB:O74885

Function

alpha-ketoglutarate-dependent xanthine dioxygenase activityGO:0097641
Substrates: xanthine 2-oxoglutarate O2
Products: urate succinate CO2

Molybdenum-independent xanthine oxidation that evolved only in fungi; in S. pombe it supports use of xanthine as a nitrogen source, with urate then degraded by urate oxidase (uro1; downstream ureide catabolism).