mycothiol S-conjugate catabolism

Reactome:R-MTU-879325

Mycobacterium tuberculosis Mca hydrolyzes detoxification conjugates of mycothiol to an N-acetyl-L-cysteine S-conjugate and glucosaminyl-inositol. Mca binds iron under anaerobic purification and zinc under aerobic purification; the native Reactome zinc complex describes the latter condition.

Pathway type

biopax pathway

Organism scope

Mycobacterium tuberculosis NCBITaxon:1773

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Pathway network

10 nodes · 14 asserted directed edges

Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.

Reaction / activity
Chemical / cofactor
Protein / complex
Cell / process context
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Mycobacterium tuberculosis `NCBITaxon:1773`	taxon
H2O `CHEBI:15377`	small molecule
Zn2+ `CHEBI:29105`	cofactor
mca `UniProtKB:P9WJN1`	protein
mca:Zn2+ `Reactome:R-MTU-879260`	complex
cytosol `GO:0005829`	cellular component
mycothiol S-conjugate `CHEBI:59633`	small molecule
S-substituted N-acetyl-L-cysteinate `CHEBI:58718`	small molecule
1D-myo-inositol 2-ammonio-2-deoxy-alpha-D-glucopyranoside `CHEBI:58886`	small molecule
iron(2+) `CHEBI:29033`	cofactor
Mca hydrolyzes mycothiol S-conjugates to mercapturic-acid conjugates and glucosaminyl-inositol `Reactome:R-MTU-879281`	molecular activity	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
H2O `CHEBI:15377`	consumes	Mca hydrolyzes mycothiol S-conjugates to mercapturic-acid conjugates and glucosaminyl-inositol `Reactome:R-MTU-879281`	Reactome:R-MTU-879325 Source assertion: BioPAX BiochemicalReaction1 lists H2O on its left side with LEFT-TO-RIGHT conversionDirection. Source location `#BiochemicalReaction1/bp:left/#SmallMolecule2`
Mca hydrolyzes mycothiol S-conjugates to mercapturic-acid conjugates and glucosaminyl-inositol `Reactome:R-MTU-879281`	occurs_in	cytosol `GO:0005829`	Reactome:R-MTU-879325 Source assertion: The physical participants of BioPAX BiochemicalReaction1 are assigned to the cytosol. Source location `#BiochemicalReaction1; participating physicalEntity/bp:cellularLocation/#CellularLocationVocabulary1`
mca:Zn2+ `Reactome:R-MTU-879260`	catalyzes The native zinc-bound Mca assembly represents the aerobic purified form; Fe2+ is favored under physiological anaerobic conditions (PMID:26044118).	Mca hydrolyzes mycothiol S-conjugates to mercapturic-acid conjugates and glucosaminyl-inositol `Reactome:R-MTU-879281`	Reactome:R-MTU-879325 Source assertion: BioPAX Catalysis1 identifies mca:Zn2+ as the controller of BiochemicalReaction1. Source location `#Catalysis1/bp:controller/#Complex1; bp:controlled/#BiochemicalReaction1`
H2O `CHEBI:15377`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-879325 Source assertion: BioPAX SmallMolecule2 assigns H2O to the cytosol. Source location `#SmallMolecule2/bp:cellularLocation/#CellularLocationVocabulary1`
Zn2+ `CHEBI:29105`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-879325 Source assertion: BioPAX SmallMolecule5 assigns Zn2+ to the cytosol. Source location `#SmallMolecule5/bp:cellularLocation/#CellularLocationVocabulary1`
mca `UniProtKB:P9WJN1`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-879325 Source assertion: BioPAX Protein1 assigns mca to the cytosol. Source location `#Protein1/bp:cellularLocation/#CellularLocationVocabulary1`
mca:Zn2+ `Reactome:R-MTU-879260`	located_in	cytosol `GO:0005829`	Reactome:R-MTU-879325 Source assertion: BioPAX Complex1 assigns mca:Zn2+ to the cytosol. Source location `#Complex1/bp:cellularLocation/#CellularLocationVocabulary1`
mca:Zn2+ `Reactome:R-MTU-879260`	has_part	Zn2+ `CHEBI:29105`	Reactome:R-MTU-879325 Source assertion: BioPAX Complex1 includes Zn2+ as a component of mca:Zn2+. Source location `#Complex1/bp:component/#SmallMolecule5`
mca:Zn2+ `Reactome:R-MTU-879260`	has_part	mca `UniProtKB:P9WJN1`	Reactome:R-MTU-879325 Source assertion: BioPAX Complex1 includes mca as a component of mca:Zn2+. Source location `#Complex1/bp:component/#Protein1`
mycothiol S-conjugate `CHEBI:59633`	consumes	Mca hydrolyzes mycothiol S-conjugates to mercapturic-acid conjugates and glucosaminyl-inositol `Reactome:R-MTU-879281`	UniProtKB:P9WJN1 Source assertion: Mca hydrolyzes a mycothiol S-conjugate to an S-substituted N-acetyl-L-cysteinate and glucosaminyl-inositol (RHEA:36543); the substrate is not unconjugated mycothiol. Source location `comments[commentType=CATALYTIC ACTIVITY].reaction[RHEA:36543]`
Mca hydrolyzes mycothiol S-conjugates to mercapturic-acid conjugates and glucosaminyl-inositol `Reactome:R-MTU-879281`	produces	S-substituted N-acetyl-L-cysteinate `CHEBI:58718`	UniProtKB:P9WJN1 Source assertion: Mca hydrolyzes a mycothiol S-conjugate to an S-substituted N-acetyl-L-cysteinate and glucosaminyl-inositol (RHEA:36543); the substrate is not unconjugated mycothiol. Source location `comments[commentType=CATALYTIC ACTIVITY].reaction[RHEA:36543]`
Mca hydrolyzes mycothiol S-conjugates to mercapturic-acid conjugates and glucosaminyl-inositol `Reactome:R-MTU-879281`	produces	1D-myo-inositol 2-ammonio-2-deoxy-alpha-D-glucopyranoside `CHEBI:58886`	UniProtKB:P9WJN1 Source assertion: Mca hydrolyzes a mycothiol S-conjugate to an S-substituted N-acetyl-L-cysteinate and glucosaminyl-inositol (RHEA:36543); the substrate is not unconjugated mycothiol. Source location `comments[commentType=CATALYTIC ACTIVITY].reaction[RHEA:36543]`
iron(2+) `CHEBI:29033`	enables Cofactor assignment is conditional: anaerobic Fe2+ form; the retained Reactome Zn2+ complex is the aerobic form.	Mca hydrolyzes mycothiol S-conjugates to mercapturic-acid conjugates and glucosaminyl-inositol `Reactome:R-MTU-879281`	PMID:26044118 Source assertion: Mca purified under anaerobic conditions contains stoichiometric Fe2+; the authors favor Fe2+-dependent activity under physiological conditions. Source location `Abstract: anaerobic versus aerobic Halo-Mca pull-down experiments`
mca `UniProtKB:P9WJN1`	has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000255 (HAMAP-Rule:MF_01482); ECO:0000269 (PubMed:26044118) Appears to be a Fe(2+)-dependent enzyme under physiological anaerobic conditions (PubMed:26044118). Binds Zn(2+) under aerobic conditions; this experimental artifact could become biologically relevant under oxidatively stressed conditions, such as those encountered inside activated macrophages (PubMed:14556638, PubMed:26044118). UniProt note evidence: ECO:0000269 (PubMed:14556638); ECO:0000269 (PubMed:26044118)	iron(2+) `CHEBI:29033`	UniProtKB:P9WJN1 Source assertion: UniProtKB:P9WJN1 annotates CHEBI:29033 as a cofactor of this protein. Source location https://rest.uniprot.org/uniprotkb/stream?query=accession%3AP02918+OR+accession%3AP02919+OR+accession%3AP06721+OR+accession%3AP07862+OR+accession%3AP08373+OR+accession%3AP0A6B4+OR+accession%3AP0A6W3+OR+accession%3AP0A749+OR+accession%3AP0A759+OR+accession%3AP0ABG4+OR+accession%3AP0ACC7+OR+accession%3AP0AD68+OR+accession%3AP0AE16+OR+accession%3AP0AF16+OR+accession%3AP0AF18+OR+accession%3AP11880+OR+accession%3AP13016+OR+accession%3AP14900+OR+accession%3AP17169+OR+accession%3AP17443+OR+accession%3AP17952+OR+accession%3AP22188+OR+accession%3AP22634+OR+accession%3AP29012+OR+accession%3AP31120+OR+accession%3AP37773+OR+accession%3AP46022+OR+accession%3AP60932+OR+accession%3AP75949+OR+accession%3AP75959+OR+accession%3AP76008+OR+accession%3AP76535+OR+accession%3AP76577+OR+accession%3AP77272+OR+accession%3AP77570+OR+accession%3AP95189+OR+accession%3AP9WFZ5+OR+accession%3AP9WJM7+OR+accession%3AP9WJM9+OR+accession%3AP9WJN1+OR+accession%3AP9WKI1+OR+accession%3AP9WMY7+OR+accession%3AP9WN11+OR+accession%3AP9WQ19+OR+accession%3AP9WQ21+OR+accession%3AP9WQ23+OR+accession%3AQ2TL65&format=json&fields=accession%2Cprotein_name%2Cxref_sgd%2Ccc_cofactor%2Corganism_id%2Ccc_caution [sha256:f2a2d9df603885068af58d89787438192b8c396d89a4cc931ac7bbab93a74c5c] #/results/32/comments/0/cofactors/0; /results/32/comments/0/note

References

Reactome:R-MTU-879281 Reactome reaction R-MTU-879281
PMID:14556638 Characterization of Mycobacterium tuberculosis mycothiol S-conjugate amidase
Reactome:R-MTU-879325 R-MTU-879325 native structured pathway source (source version: Reactome BioPAX 97)
UniProtKB:P9WJN1 Mycothiol S-conjugate amidase Mca; curated catalytic reaction RHEA:36543 (source version: UniProt entry retrieved 2026-10-05)
PMID:26044118 Identity of cofactor bound to mycothiol conjugate amidase (Mca) influenced by expression and purification conditions

Curation history

2026-10-05T06:16:56Z Codex
- EDIT — Review complete causal graph against native sources and correct unsupported or omitted relationships
  All native sides, controllers, complexes, cofactors and cytosol locations inspected; source comments are not attributed as quotations from cited papers. Replaced incorrect free-MSH/S-acetylcysteine identities with RHEA36543 conjugate classes; qualified metal dependence using PMID26044118. Every native record was inspected; see reports/causal-graph-diagram-review.json for native-object counts, exclusions and identity corrections. Semantic validation and native GraphId locator checks passed; authority snapshots and full corpus gates are coordinated separately.
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