Methylmalonic aciduria type A protein (MMAA) (Dobson et al. 2002) is thought to act as a chaperone to MUT and is suggested to play a dual role with regards to MUT protection and reactivation.
Defects in MMAA cause methylmalonic aciduria type cblA (MMAA aka methylmalonic aciduria type A or vitamin B12-responsive methylmalonicaciduria of cblA complementation type; MIM:251100). Affected individuals accumulate methylmalonic acid in the blood and urine and are prone to potentially life threatening acidotic crises in infancy or early childhood (Dobson et al. 2002, Lerner-Ellis et al. 2004).",
"cellular_location": "mitochondrial matrix",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q8IVH4-1",
"P22033-1"
],
"evidence": [
{
"id": "R-HSA-3159259",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-3159259"
}
]
},
{
"id": "R-HSA-3322135",
"name": "Defective MMAA does not protect MUT",
"equation": "",
"summary": "Methylmalonic aciduria type A protein (MMAA) is thought to act as a chaperone to MUT, the enzyme which utilises adenosylcobalamin (AdoCbl) as a cofactor. MMAA is suggested to play a dual role with regards to MUT protection and reactivation. Some AdoCbl-dependent enzymes undergo suicide inactivation after catalysis due to the oxidative inactivation of Cbl. MMAA is thought to play a protective role to prevent MUT being inactivated in this way. Defects in MMAA cause methylmalonic aciduria type cblA (cblA aka methylmalonic aciduria type A or vitamin B12-responsive methylmalonicaciduria of cblA complementation type; MIM:251100). Affected individuals accumulate methylmalonic acid in the blood and urine and are prone to potentially life threatening acidotic crises in infancy or early childhood. Mutations causing cblA include MMAA Q95*, R145*, Y207C and D87Ifs*11 (Dobson et al. 2002, Lerner-Ellis et al. 2004).",
"cellular_location": "mitochondrial matrix",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q8IVH4-1",
"P22033-1"
],
"evidence": [
{
"id": "R-HSA-3322135",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-3322135"
}
]
},
{
"id": "R-HSA-3322971",
"name": "Defective MUT does not isomerise L-MM-CoA to SUCC-CoA",
"equation": "",
"summary": "Methylmalonyl CoA mutase (MUT aka MCM) (Jansen et al. 1989) utilises adenosylcobalamin (AdoCbl) as a cofactor catalyzes interchange of a carbonylCoA group and a hydrogen atom in conversion of methylmalonyl CoA to form succinyl CoA, a precursor for the citric acid cycle. MUT has a homodimeric structure and is located in the mitochondrial matrix. Defects in MUT cause methylmalonic aciduria, mut type (MMAM; MIM:251000), an often fatal disorder of organic acid metabolism (Worgan et al. 2006). Patients with no residual MUT activity are defined as MMA mut(0); those with some residual MUT activity are defined as MMA mut(-). Mutations causing MMA mut(0) type of disorder include Q17*, W105R, A378E, R93H, G623R, G703R, N219Y, R108C and G215S (Ledley et al. 1990, Jansen & Ledley 1990, Raff et al 1991, Ledley & Rosenblatt 1997, Qureshi et al. 1994, Acquaviva et al. 2001, Acquaviva et al. 2005, Berger et al. 2001, Worgan et al. 2006, Cavicchi et al. 2006).",
"cellular_location": "mitochondrial matrix",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q8IVH4-1",
"P22033-1"
],
"evidence": [
{
"id": "R-HSA-3322971",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-3322971"
}
]
},
{
"id": "R-HSA-71010",
"name": "MUT isomerises L-MM-CoA to SUCC-CoA",
"equation": "",
"summary": "Methylmalonyl CoA mutase (MUT aka MCM) (Jansen et al. 1989) utilises adenosylcobalamin (AdoCbl) as a cofactor and catalyzes interchange of a carbonyl-CoA group and a hydrogen atom in conversion of methylmalonyl CoA to form succinyl CoA, a precursor for the citric acid cycle. MUT has a homodimeric structure and is located in the mitochondrial matrix. Defects in MUT cause methylmalonic aciduria, mut type (MMAM; MIM:251000), an often fatal disorder of organic acid metabolism (Worgan et al. 2006).
Methylmalonic aciduria type A protein (MMAA) is thought to act as a chaperone to MUT, the enzyme which utilises adenosylcobalamin (AdoCbl) as a cofactor. MMAA is suggested to play a dual role with regards to MUT protection and reactivation. Some AdoCbl-dependent enzymes undergo suicide inactivation after catalysis due to the oxidative inactivation of Cbl. MMAA is thought to play a protective role to prevent MUT being inactivated in this way. After the catalytic cycle when MUT is inactive, MMAA increases the enzymatic activity of MUT through exchange of the damaged cofactor. Whether this happens via GTP-mediated hydrolysis is unknown at present (Takahashi-Iniguez et al. 2011, Froese et al. 2010). Bacterial AdoCbl-containing enzymes possess reactivating factors which release the inactivated cofactor to allow the resulting apoenzyme to reconstitute into an active form. A bacterial orthologue of MMAA, MeaB, forms a stable complex with MUT and plays a role in its protection and reactivation (Padovani & Banerjee 2006).
Defects in MMAA cause methylmalonic aciduria type cblA (cblA aka methylmalonic aciduria type A or vitamin B12-responsive methylmalonicaciduria of cblA complementation type; MIM:251100). Affected individuals accumulate methylmalonic acid in the blood and urine and are prone to potentially life threatening acidotic crises in infancy or early childhood (Dobson et al. 2002, Lerner-Ellis et al. 2004).",
"cellular_location": "mitochondrial matrix",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q8IVH4-1",
"P22033-1"
],
"evidence": [
{
"id": "R-HSA-71010",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-71010"
}
]
}
],
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{
"uniprot_ac": "D3ZKG1",
"gene_name": "Mmut",
"activity": [
{
"ec_number": "5.4.99.2",
"activity": "(R)-methylmalonyl-CoA = succinyl-CoA.",
"evidence": [
{
"id": "D3ZKG1",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprot/D3ZKG1"
}
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},
{
"ec_number": "5.4.99.2",
"activity": "",
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"url": "https://www.uniprot.org/uniprot/D3ZKG1"
}
]
}
]
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{
"uniprot_ac": "P16332",
"gene_name": "Mmut",
"activity": [
{
"ec_number": "5.4.99.2",
"activity": "(R)-methylmalonyl-CoA = succinyl-CoA.",
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"id": "P16332",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprot/P16332"
}
]
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{
"ec_number": "5.4.99.2",
"activity": "",
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}
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}
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{
"ec_number": "5.4.99.2",
"activity": "(R)-methylmalonyl-CoA = succinyl-CoA.",
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}
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}
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{
"ec_number": "3.6.-.-",
"activity": "",
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"id": "Q8IVH4",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprot/Q8IVH4"
}
]
}
]
}
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{
"name": "homologset.mgi",
"label": "MGI Homologs"
},
{
"name": "homologset.oma",
"label": "OMA Homologs"
}
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