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Literature summary for 5.4.99.2 extracted from

  • Takahashi-Iniguez, T.; Gonzalez-Noriega, A.; Michalak, C.; Flores, M.E.
    Human MMAA induces the release of inactive cofactor and restores methylmalonyl-CoA mutase activity through their complex formation (2017), Biochimie, 142, 191-196 .
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
hMMAA hMCM loses activity during catalysis, but the interaction with human MMAA (hMMAA), a GTPase protein, avoids this loss or restores hMCM activity. Formation and accumulation of OH2Cbl, the oxidized form of cofactor AdoCbl formed during catalysis, is the cause of hMCM inactivation. The complex formation of hMCM/hMMAA decreases the rate of oxidized cofactor formation, protecting the hMCM enzyme. hMMAA is able to remove the damaged cofactor through GTP hydrolysis.a modification in the kinetic parameters of hMCM in presence of hMMAA is observed. No activity is recovered in the presence of hMMAAwith GMPPNP, confirming the need of GTP hydrolysis for this cofactor removal. In vivo localization of hMMAA and its colocalization with hMCM in human fibroblasts mitochondria. hMMAAis localized in both the cytoplasm and mitochondria but in less abundance and distribution than enzyme hMCM Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Michaelis-Menten kinetics Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm enzyme hMCM preferably locates in mitochondria, with small amounts of protein in the cytoplasm Homo sapiens 5737
-
mitochondrion enzyme hMCM preferably locates in mitochondria, with small amounts of protein in the cytoplasm Homo sapiens 5739
-
additional information immunohistochemic analysis of subcellular localization in fibroblasts, overview Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(R)-methylmalonyl-CoA Homo sapiens
-
succinyl-CoA
-
r

Organism

Organism UniProt Comment Textmining
Homo sapiens P22033
-
-

Source Tissue

Source Tissue Comment Organism Textmining
fibroblast
-
Homo sapiens
-
GMO2784 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(R)-methylmalonyl-CoA
-
Homo sapiens succinyl-CoA
-
r

Synonyms

Synonyms Comment Organism
hMCM
-
Homo sapiens
mitochondrial methylmalonyl-CoA mutase
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
20
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
adenosylcobalamin AdoCbl, the enzyme converts methylmalonyl-CoA to succinyl-CoA employing highly reactive radicals from its cofactor adenosylcobalamin to perform its reaction. Formation and accumulation of OH2Cbl, the oxidized form of the AdoCbl cofactor formed during catalysis, is the cause of hMCM inactivation. GTPase hMMAA is able to remove the damaged cofactor through GTP hydrolysis Homo sapiens

General Information

General Information Comment Organism
physiological function human mitochondrial methylmalonyl-CoA mutase (hMCM) is an isomerase that converts methylmalonyl-CoA to succinyl-CoA, a crucial step for the incorporation of some compounds derived from the diet into the central metabolism. hMCM employs highly reactive radicals from its cofactor (adenosylcobalamin, AdoCbl) to perform its reaction. hMCM loses activity during catalysis, but the interaction with human MMAA (hMMAA), a GTPase protein, avoids this loss or restores hMCM activity. Formation and accumulation of OH2Cbl, the oxidized form of cofactor AdoCbl formed during catalysis, is the cause of hMCM inactivation. The complex formation of hMCM/hMMAA decreases the rate of oxidized cofactor formation, protecting the hMCM enzyme. hMMAA is able to remove the damaged cofactor through GTP hydrolysis.a modification in the kinetic parameters of hMCM in presence of hMMAA is observed Homo sapiens