Aflatoxin activation and detoxification (Homo sapiens)

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7, 24, 25, 312412, 182, 27111, 5, 28246, 14, 15, 20, 2924, 251721, 22, 3010, 2417138, 16, 19, 23, 323, 9, 2611, 282618nucleoplasmendoplasmic reticulum lumenendoplasmic reticulum lumencytosolAFXBOunknown NATAFB1NADPHNADP+AFXBO-C AFBDHDAc-CoAAFBDHODPEP2 AFNBOZn2+ AFNBO-C AKR7A3 CoA-SHCYP2A13 NADPHAFXBO-NAC,AFNBO-NACH2OO2ACY3:Zn2+ dimerAFXBO,AFNBOCYP3A5 DPEP1,2,3 dimersCYP3A4 AFXBO-CG CYP1A2,3A4GGT5(1-387) AFB1AFXBO-CG,AFNBO-CGAKR7L Zn2+ H2OAFXBO-SG AKR7A2 AFXBO AFNBO-C ACY1 ACY1:Zn2+ dimerGGT3P(381-568) MGST1 GGT7(1-472) O2NADP+NADP+Zn2+ H2OGGT5(388-586) GGT dimersAFXBOH+GSHGGT7(473-662) NADPHMGST3 AFBDOHH+AFXBO-SG DNA CYP3A4 AFNBO-CG CYP1A2,3A4,3A5,2A13NADP+CYP1A2AFNBO NADP+O2AFXBO:DNAAFM1GGT6(?-493) L-GluAFM1ECYP1A2 H+GGT1(381-569) AFXBO-SG,AFNBO-SGAKR dimersH2ODNAH2OH2OAFXBO-NAC GGT6(1-?) H+ACY3 AFXBO MGST2 AFXBO-C,AFNBO-CAFXBO-SG,AFNBO-SGCH3COO-AFXBO-C NADPHMGST trimersGGT3P(1-380) CYP3A4,5CYP2A13AFNBO-NAC CYP3A5 DPEP1 DPEP3 AFQ1H2OCYP1A2 AFNBO-SG CYP3A4 AFNBO-SG GlyAFXBO-C,AFNBO-CH2OGGT1(1-380) 4, 26


Description

Aflatoxins are among the principal mycotoxins produced as secondary metabolites by the molds Aspergillus flavus and Aspergillus parasiticus that contaminate economically important food and feed crops (Wild & Turner 2002). Aflatoxin B1 (AFB1) is the most potent naturally occurring carcinogen known and is also an immunosuppressant. It is a potent hepatocarcinogenic agent in many species, and has been implicated in the etiology of human hepatocellular carcinoma. Poultry, especially turkeys, are extremely sensitive to the toxic and carcinogenic action of AFB1 present in animal feed, resulting in multi-million dollar losses to the industry. Discerning the biochemical and molecular mechanisms of this extreme sensitivity of poultry to AFB1 will help with the development of new strategies to increase aflatoxin resistance (Rawal et al. 2010, Diaz & Murcia 2011).


AFB1 has one major genotoxic metabolic fate, conversion to AFXBO, and several others that are less mutagenic but that can still be quite toxic. AFB1 can be oxidised to the toxic AFB1 exo 8,9 epoxide (AFXBO) product by several cytochrome P450 enzymes, especially P450 3A4 in the liver. This 8,9 epoxide can react with the N7 atom of a guanyl base of DNA to produce adducts by intercalating between DNA base pairs. The exo epoxide is unstable in solution, however, and can react spontaneously to form a diol that is no longer reactive with DNA. The diol product in turn undergoes base-catalysed rearrangement to a dialdehyde that can react with protein lysine residues. AFB1 can also be metabolised to products (AFQ1, AFM1, AFM1E) which have far less genotoxic consequences than AFB1. The main route of detoxification of AFB1 is conjugation of its reactive 8,9-epoxide form with glutathione (GSH). This reaction is carried out by trimeric glutathione transferases (GSTs), providing a chemoprotective mechanism against toxicity. Glutathione conjugates are usually excreted as mercapturic acids in urine (Guengerich et al. 1998, Hamid et al. 2013). The main metabolic routes of aflatoxin in humans are described here. View original pathway at Reactome.

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Pathway is converted from Reactome ID: 5423646
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Reactome version: 73
Reactome Author 
Reactome Author: Jassal, Bijay

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Bibliography

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History

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CompareRevisionActionTimeUserComment
115002view16:53, 25 January 2021ReactomeTeamReactome version 75
113446view11:52, 2 November 2020ReactomeTeamReactome version 74
112646view16:03, 9 October 2020ReactomeTeamReactome version 73
101561view11:43, 1 November 2018ReactomeTeamreactome version 66
101097view21:26, 31 October 2018ReactomeTeamreactome version 65
100626view20:00, 31 October 2018ReactomeTeamreactome version 64
100177view16:45, 31 October 2018ReactomeTeamreactome version 63
99727view15:12, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93959view13:47, 16 August 2017ReactomeTeamreactome version 61
93555view11:27, 9 August 2017ReactomeTeamreactome version 61
87079view14:22, 18 July 2016MkutmonOntology Term : 'aflatoxin metabolic pathway' added !
86657view09:23, 11 July 2016ReactomeTeamreactome version 56
83239view10:28, 18 November 2015ReactomeTeamVersion54
81346view12:52, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACY1 ProteinQ03154 (Uniprot-TrEMBL)
ACY1:Zn2+ dimerComplexR-HSA-5433068 (Reactome)
ACY3 ProteinQ96HD9 (Uniprot-TrEMBL)
ACY3:Zn2+ dimerComplexR-HSA-5433069 (Reactome)
AFB1MetaboliteCHEBI:2504 (ChEBI)
AFBDHDMetaboliteCHEBI:53106 (ChEBI)
AFBDHOMetaboliteCHEBI:53107 (ChEBI)
AFBDOHMetaboliteCHEBI:53108 (ChEBI)
AFM1MetaboliteCHEBI:78576 (ChEBI)
AFM1EMetaboliteCHEBI:78577 (ChEBI)
AFNBO MetaboliteCHEBI:78586 (ChEBI)
AFNBO-C MetaboliteCHEBI:78578 (ChEBI)
AFNBO-CG MetaboliteCHEBI:78579 (ChEBI)
AFNBO-NAC MetaboliteCHEBI:78580 (ChEBI)
AFNBO-SG MetaboliteCHEBI:78581 (ChEBI)
AFNBOMetaboliteCHEBI:78586 (ChEBI)
AFQ1MetaboliteCHEBI:78582 (ChEBI)
AFXBO MetaboliteCHEBI:30725 (ChEBI)
AFXBO,AFNBOComplexR-ALL-5423723 (Reactome)
AFXBO-C MetaboliteCHEBI:78583 (ChEBI)
AFXBO-C,AFNBO-CComplexR-ALL-5490231 (Reactome)
AFXBO-C,AFNBO-CComplexR-ALL-5490250 (Reactome)
AFXBO-CG MetaboliteCHEBI:78584 (ChEBI)
AFXBO-CG,AFNBO-CGComplexR-ALL-5490235 (Reactome)
AFXBO-NAC MetaboliteCHEBI:78585 (ChEBI)
AFXBO-NAC,AFNBO-NACComplexR-ALL-5490236 (Reactome)
AFXBO-SG MetaboliteCHEBI:78587 (ChEBI)
AFXBO-SG,AFNBO-SGComplexR-ALL-5423730 (Reactome)
AFXBO-SG,AFNBO-SGComplexR-ALL-5490253 (Reactome)
AFXBO:DNAComplexR-ALL-5423670 (Reactome)
AFXBOMetaboliteCHEBI:30725 (ChEBI)
AKR dimersComplexR-HSA-5423668 (Reactome)
AKR7A2 ProteinO43488 (Uniprot-TrEMBL)
AKR7A3 ProteinO95154 (Uniprot-TrEMBL)
AKR7L ProteinQ8NHP1 (Uniprot-TrEMBL)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
CH3COO-MetaboliteCHEBI:15366 (ChEBI)
CYP1A2 ProteinP05177 (Uniprot-TrEMBL)
CYP1A2,3A4,3A5,2A13ComplexR-HSA-5423602 (Reactome)
CYP1A2,3A4ComplexR-HSA-5423625 (Reactome)
CYP1A2ProteinP05177 (Uniprot-TrEMBL)
CYP2A13 ProteinQ16696 (Uniprot-TrEMBL)
CYP2A13ProteinQ16696 (Uniprot-TrEMBL)
CYP3A4 ProteinP08684 (Uniprot-TrEMBL)
CYP3A4,5ComplexR-HSA-5423680 (Reactome)
CYP3A5 ProteinP20815 (Uniprot-TrEMBL)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
DNA R-ALL-29428 (Reactome)
DNAR-ALL-29428 (Reactome)
DPEP1 ProteinP16444 (Uniprot-TrEMBL)
DPEP1,2,3 dimersComplexR-HSA-2162149 (Reactome)
DPEP2 ProteinQ9H4A9 (Uniprot-TrEMBL)
DPEP3 ProteinQ9H4B8 (Uniprot-TrEMBL)
GGT dimersComplexR-HSA-1247946 (Reactome)
GGT1(1-380) ProteinP19440 (Uniprot-TrEMBL)
GGT1(381-569) ProteinP19440 (Uniprot-TrEMBL)
GGT3P(1-380) ProteinA6NGU5 (Uniprot-TrEMBL)
GGT3P(381-568) ProteinA6NGU5 (Uniprot-TrEMBL)
GGT5(1-387) ProteinP36269 (Uniprot-TrEMBL)
GGT5(388-586) ProteinP36269 (Uniprot-TrEMBL)
GGT6(1-?) ProteinQ6P531 (Uniprot-TrEMBL)
GGT6(?-493) ProteinQ6P531 (Uniprot-TrEMBL)
GGT7(1-472) ProteinQ9UJ14 (Uniprot-TrEMBL)
GGT7(473-662) ProteinQ9UJ14 (Uniprot-TrEMBL)
GSHMetaboliteCHEBI:16856 (ChEBI)
GlyMetaboliteCHEBI:57305 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
L-GluMetaboliteCHEBI:29985 (ChEBI)
MGST trimersComplexR-HSA-176042 (Reactome)
MGST1 ProteinP10620 (Uniprot-TrEMBL)
MGST2 ProteinQ99735 (Uniprot-TrEMBL)
MGST3 ProteinO14880 (Uniprot-TrEMBL)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
O2MetaboliteCHEBI:15379 (ChEBI)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
unknown NATR-HSA-5490258 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ACY1:Zn2+ dimermim-catalysisR-HSA-5433074 (Reactome)
ACY3:Zn2+ dimermim-catalysisR-HSA-9638046 (Reactome)
AFB1R-HSA-156526 (Reactome)
AFB1R-HSA-5423664 (Reactome)
AFB1R-HSA-5423672 (Reactome)
AFB1R-HSA-5423678 (Reactome)
AFBDHDArrowR-HSA-5423656 (Reactome)
AFBDHDR-HSA-5423694 (Reactome)
AFBDHOArrowR-HSA-5423694 (Reactome)
AFBDHOR-HSA-5423637 (Reactome)
AFBDOHArrowR-HSA-5423637 (Reactome)
AFM1ArrowR-HSA-5423678 (Reactome)
AFM1EArrowR-HSA-5423647 (Reactome)
AFM1R-HSA-5423647 (Reactome)
AFNBOArrowR-HSA-5423672 (Reactome)
AFQ1ArrowR-HSA-5423664 (Reactome)
AFXBO,AFNBOR-HSA-5423653 (Reactome)
AFXBO-C,AFNBO-CArrowR-HSA-5433067 (Reactome)
AFXBO-C,AFNBO-CArrowR-HSA-5433074 (Reactome)
AFXBO-C,AFNBO-CArrowR-HSA-5490269 (Reactome)
AFXBO-C,AFNBO-CArrowR-HSA-9638046 (Reactome)
AFXBO-C,AFNBO-CR-HSA-5433066 (Reactome)
AFXBO-C,AFNBO-CR-HSA-5490269 (Reactome)
AFXBO-CG,AFNBO-CGArrowR-HSA-5433072 (Reactome)
AFXBO-CG,AFNBO-CGR-HSA-5433067 (Reactome)
AFXBO-NAC,AFNBO-NACArrowR-HSA-5433066 (Reactome)
AFXBO-NAC,AFNBO-NACR-HSA-5433074 (Reactome)
AFXBO-NAC,AFNBO-NACR-HSA-9638046 (Reactome)
AFXBO-SG,AFNBO-SGArrowR-HSA-5423653 (Reactome)
AFXBO-SG,AFNBO-SGArrowR-HSA-5490230 (Reactome)
AFXBO-SG,AFNBO-SGR-HSA-5433072 (Reactome)
AFXBO-SG,AFNBO-SGR-HSA-5490230 (Reactome)
AFXBO:DNAArrowR-HSA-5423632 (Reactome)
AFXBOArrowR-HSA-156526 (Reactome)
AFXBOArrowR-HSA-5423728 (Reactome)
AFXBOR-HSA-5423632 (Reactome)
AFXBOR-HSA-5423656 (Reactome)
AFXBOR-HSA-5423728 (Reactome)
AKR dimersmim-catalysisR-HSA-5423637 (Reactome)
Ac-CoAR-HSA-5433066 (Reactome)
CH3COO-ArrowR-HSA-5433074 (Reactome)
CH3COO-ArrowR-HSA-9638046 (Reactome)
CYP1A2,3A4,3A5,2A13mim-catalysisR-HSA-156526 (Reactome)
CYP1A2,3A4mim-catalysisR-HSA-5423672 (Reactome)
CYP1A2mim-catalysisR-HSA-5423678 (Reactome)
CYP2A13mim-catalysisR-HSA-5423647 (Reactome)
CYP3A4,5mim-catalysisR-HSA-5423664 (Reactome)
CoA-SHArrowR-HSA-5433066 (Reactome)
DNAR-HSA-5423632 (Reactome)
DPEP1,2,3 dimersmim-catalysisR-HSA-5433067 (Reactome)
GGT dimersmim-catalysisR-HSA-5433072 (Reactome)
GSHR-HSA-5423653 (Reactome)
GlyArrowR-HSA-5433067 (Reactome)
H+R-HSA-156526 (Reactome)
H+R-HSA-5423637 (Reactome)
H+R-HSA-5423647 (Reactome)
H+R-HSA-5423664 (Reactome)
H+R-HSA-5423672 (Reactome)
H+R-HSA-5423678 (Reactome)
H2OArrowR-HSA-156526 (Reactome)
H2OArrowR-HSA-5423647 (Reactome)
H2OArrowR-HSA-5423664 (Reactome)
H2OArrowR-HSA-5423672 (Reactome)
H2OArrowR-HSA-5423678 (Reactome)
H2OR-HSA-5423656 (Reactome)
H2OR-HSA-5423694 (Reactome)
H2OR-HSA-5433072 (Reactome)
H2OR-HSA-5433074 (Reactome)
H2OR-HSA-9638046 (Reactome)
L-GluArrowR-HSA-5433072 (Reactome)
MGST trimersmim-catalysisR-HSA-5423653 (Reactome)
NADP+ArrowR-HSA-156526 (Reactome)
NADP+ArrowR-HSA-5423637 (Reactome)
NADP+ArrowR-HSA-5423647 (Reactome)
NADP+ArrowR-HSA-5423664 (Reactome)
NADP+ArrowR-HSA-5423672 (Reactome)
NADP+ArrowR-HSA-5423678 (Reactome)
NADPHR-HSA-156526 (Reactome)
NADPHR-HSA-5423637 (Reactome)
NADPHR-HSA-5423647 (Reactome)
NADPHR-HSA-5423664 (Reactome)
NADPHR-HSA-5423672 (Reactome)
NADPHR-HSA-5423678 (Reactome)
O2R-HSA-156526 (Reactome)
O2R-HSA-5423647 (Reactome)
O2R-HSA-5423664 (Reactome)
O2R-HSA-5423672 (Reactome)
O2R-HSA-5423678 (Reactome)
R-HSA-156526 (Reactome) Aflatoxin B1 (AFB1) requires microsomal oxidation to produce epoxides which cause the toxic and carcinogenic effects. In humans, cytochrome P450 enzymes produce epoxide stereoisomers of AFB1, the most potent being aflatoxin exo-8,9-oxide (AFXBO). This conversion is carried out by at least four P450s; 1A2, 3A4, 3A5 and 2A13. CYP3A4 mainly produces the exo form whereas CYP1A2 produces a racemic mixture of exo and endo forms (Gallagher et al. 1996, He et al. 2006).
R-HSA-5423632 (Reactome) Aflatoxin B1 (AFB1), a category I known human carcinogen and the most potent genotoxic agent, is mutagenic in many model systems. Aflatoxin B1 exo-8,9-epoxide (AFXBO) binds to DNA to form the predominant 8,9-dihydro-8-(N7 guanyl)-9-hydroxy-AFB1 (AFB1-N7-Gua) adduct. AFB1-N7-Gua confers the mutagenic properties of the compound (Raney et al. 1993, Bedard & Massey 2006).
R-HSA-5423637 (Reactome) Aflatoxin B1 aldehyde reductases (AKR7A2, AKR7A3 and AKR7L) are dimeric, cytosolic, NADPH-dependent enzymes able to catalyse the reduction of aflatoxin B1 dialdehyde (AFBDHO) to aflatoxin B1-6,8-dialcohol (AFBDOH) (Ellis et al. 2003, Bodreddigari et al. 2008, Ireland et al. 1998, Guengerich et al. 2001). AKRs can turnover a vast range of substrates, including drugs, carcinogens, and reactive aldehydes. They play central roles in the metabolism of these agents, leading to either their bioactivation or detoxication (Jin & Penning 2007). The dialcohol is excreted in urine by conjugation with glucuronide (not shown here).
R-HSA-5423647 (Reactome) Cytochrome P450 2A13 is able to oxidise aflatoxin M1 (AFM1) to the reactive aflatoxin M1 epoxide (AFM1E) (He et al. 2006). AFM1E is less carcinogenic or mutagenic than aflatoxin B1-exo-8,9-epoxide (AFBO), but is equally toxic. AFM1E would usually be detoxified by conjugation with glutathione, eventually excreted in urine as a mercapturic acid (not shown here).
R-HSA-5423653 (Reactome) The microsomal glutathione S-transferases (MGSTs) catalyse the nucleophilic attack by reduced glutathione (GSH) on nonpolar compounds that contain an electrophilic C, N, or S atom. Three major families of proteins are widely distributed in nature. The cytosolic and mitochondrial GST families comprise soluble enzymes that are only distantly related whilst the third family comprises microsomal GST, referred to as membrane-associated proteins in eicosanoid and glutathione (MAPEG) metabolism. Three members of this family function as detoxification enzymes, MGST1-3 (DeJong et al. 1988, Kelner et al. 1996, Jakobsson et al. 1996, Jakobsson et al. 1997). Electron crystallography studies in rat Mgst1 indicate these enzymes function as homotrimers (Holm et al. 2002). Both aflatoxin B1 exo- and endo-epoxides (AFXBO and AFNBO) conjugate with glutathione. These conjugates are eventually excreted in urine as mercapturic acids.
R-HSA-5423656 (Reactome) The exo- and endo-epoxides of aflatoxin B1 are unstable in water and can undergo rapid non-enzymatic hydrolysis to AFB1-8,9-dihydrodiol (AFBDHD) (Johnson et al. 1997, Guengerich et al. 1998).
R-HSA-5423664 (Reactome) Metabolites that are formed from aflatoxin B1 (AFB1) include AFQ1, AFM1 and AFP1 (Gallagher et al. 1996). These metabolites and other naturally occurring aflatoxins (G1, B2 and G2) are poorer substrates for epoxidation and, consequently, are less mutagenic, carcinogenic and toxic than AFB1. AFB1 metabolites can be useful biomarkers of human exposure to aflatoxins and AFM1, AFQ1 and AFP1 have all been detected in human urine samples (Groopman et al. 1985). Cytochrome P450 3A4 and 3A5 are the predominant enzymes involved in AFQ1 (3-hydroxy aflatoxin) production (Raney et al. 1992).
R-HSA-5423672 (Reactome) Aflatoxin B1 (AFB1) requires microsomal oxidation to produce epoxides which cause the toxic and carcinogenic effects. In humans, cytochrome P450 enzymes produce epoxide stereoisomers of AFB1, the most potent being aflatoxin exo-8,9-oxide (AFNBO). CYP3A4 and CYP1A2 can also produce aflatoxin B1-endo-8,9-epoxide (Raney et al. 1992, Ueng et al. 1995).
R-HSA-5423678 (Reactome) Aflatoxin B1 (AFB1) undergoes extensive oxidation, which is catalysed by cytochrome P450s. In addition to formation of the 8,9-oxide, oxidation by CYP1A2 yields a stable metabolite, aflatoxin M1 (AFM1), that is excreted in milk and urine (Ueng et al. 1995). AFM1 is less carcinogenic or mutagenic than AFB1, but is equally toxic.
R-HSA-5423694 (Reactome) Aflatoxin B1-8,9-dihydrodiol (AFBDHD) undergoes base-catalysed rearrangement to aflatoxin B1 dialdehyde (AFBDHO) that can react with protein lysine residues (not shown here) (Guengerich et al. 1998).
R-HSA-5423728 (Reactome) For the reactive metabolite aflatoxin B1-exo-8,9-epoxide (AFBO) to react with DNA, it must translocate to the nucleus. This mechanism of translocation is thought to be simple diffusion (Guengerich et al. 1998).
R-HSA-5433066 (Reactome) An unknown cysteine-S-conjugate N-acetyltransferase (NAT) catalyses the transfer of an acetyl group from acetyl CoA (Ac-CoA) to the exo and endo forms of aflatoxin B1-cysteinyl conjugates (AFXBO-C, AFNBO-C). The resultant N-acetylcysteine-S-conjugate is termed a mercapturic acid which is readily excreted in urine (Hinchman & Ballatori 1994).
R-HSA-5433067 (Reactome) In the formation of mercapturic acid from glutathione conjugates, first a glutamate residue is hydrolysed from the conjugate then a glycine residue (Gly). The dipeptidases 1,2 and 3 (DPEP1,2,3) perform this second hydrolysis. They are membrane-bound, homodimeric enzymes which require zinc ions for activity. DPEP1 has been characterised (Satoh et al. 1993, 1994, Nitanai et al. 2002) whereas DPEP2 and 3 are thought to function as DPEP1 based on similarity.
R-HSA-5433072 (Reactome) To be excreted in urine, glutathione conjugates undergo several hydrolysis steps to form mercapturic acids which are readily excreted. The first step is the hydrolysis of a gamma-glutamyl residue from the conjugate catalysed by gamma-glutamyltransferases (GGTs). These are membrane-bound, heterodimeric enzymes composed of light and heavy peptide chains. GGT1 and 2 are well characterised while GGT3P, 5, 6 and 7 are putative transferases. Extracellular glutathione or its conjugates can be hydrolysed to give cysteinylglycine (CG, or CG conjugates) and free glutamate (L-Glu) (Heisterkamp et al. 2008, Tate & Ross 1977, Pawlak et al. 1989).
R-HSA-5433074 (Reactome) Cytosolic aminocyclases 1 and 3 (ACY1,3) can hydrolyse N-acylated amino acids and N-acylcysteine-S-conjugates (Lindner et al. 2003). They are functional as dimers and utilise zinc as a cofactor.
R-HSA-5490230 (Reactome) As glutathione conjugates of aflatoxin exo-and endo-epoxides are secreted from the cell, they undergo several hydrolysis steps before they form the mercapturic acid form which is excreted in urine (Heisterkamp et al. 2008). The mechanism of translocation is unknown.
R-HSA-5490269 (Reactome) To be transformed into mercapturic acids, the endo and exo forms of aflatoxin B1 cysteine-S-conjugates (AFNBO-C, AFXBO-C) translocate into cells (Guengerich et al. 1998, Wu et al. 2009). The mechanism of translocation is unknown.
R-HSA-9638046 (Reactome) Cytosolic aminocyclases 1 and 3 (ACY1,3) can hydrolyse N-acylated amino acids and N-acylcysteine-S-conjugates (Lindner et al. 2003). They are functional as dimers and utilise zinc as a cofactor.
unknown NATmim-catalysisR-HSA-5433066 (Reactome)
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