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Literature summary for 1.2.1.25 extracted from

  • Sperringer, J.E.; Addington, A.; Hutson, S.M.
    Branched-chain amino acids and brain metabolism (2017), Neurochem. Res., 42, 1697-1709 .
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
genes BCKDHA and BCKDHB, encoding the subunits BCKDHA and BCKDHB if the E1 component, located on chromosome 19q13.2 and 6q14.1, respectively Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3-methyl-2-oxobutanoate + CoA + NAD+ Rattus norvegicus
-
2-methylpropanoyl-CoA + CO2 + NADH + H+
-
ir
3-methyl-2-oxobutanoate + CoA + NAD+ Homo sapiens
-
2-methylpropanoyl-CoA + CO2 + NADH + H+
-
ir
3-methyl-2-oxopentanoate + CoA + NAD+ Rattus norvegicus
-
2-methylbutanoyl-CoA + CO2 + NADH + H+
-
ir
3-methyl-2-oxopentanoate + CoA + NAD+ Homo sapiens
-
2-methylbutanoyl-CoA + CO2 + NADH + H+
-
ir
4-methyl-2-oxopentanoate + CoA + NAD+ Rattus norvegicus
-
3-methylbutanoyl-CoA + CO2 + NADH + H+
-
ir
4-methyl-2-oxopentanoate + CoA + NAD+ Homo sapiens
-
3-methylbutanoyl-CoA + CO2 + NADH + H+
-
ir

Organism

Organism UniProt Comment Textmining
Homo sapiens P12694 AND P21953 subunits BCKDHA and BCKDHB of the E1 component, cf. EC 1.2.4.4
-
Rattus norvegicus
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein BCKDC activity is controlled via its phosphorylation state of the E1 subunits, with the phosphorylated form rendering the complex inactive Rattus norvegicus
phosphoprotein BCKDC activity is controlled via its phosphorylation state of the E1 subunits, with the phosphorylated form rendering the complex inactive Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
endothelium
-
Rattus norvegicus
-
endothelium
-
Homo sapiens
-
heart
-
Rattus norvegicus
-
heart
-
Homo sapiens
-
kidney
-
Rattus norvegicus
-
kidney
-
Homo sapiens
-
Kupffer cell
-
Homo sapiens
-
liver
-
Rattus norvegicus
-
liver
-
Homo sapiens
-
additional information BCKDC activity is highest in liver but present in all tissues tested. In the liver, BCKDC activity is high, with moderate activity in the kidney and heart, and limited active enzyme in skeletal muscle Rattus norvegicus
-
additional information BCKDC activity is highest in liver but present in all tissues tested. In the liver, BCKDC activity is high, with moderate activity in the kidney and heart, and limited active enzyme in skeletal muscle Homo sapiens
-
skeletal muscle
-
Rattus norvegicus
-
skeletal muscle
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3-methyl-2-oxobutanoate + CoA + NAD+
-
Rattus norvegicus 2-methylpropanoyl-CoA + CO2 + NADH + H+
-
ir
3-methyl-2-oxobutanoate + CoA + NAD+
-
Homo sapiens 2-methylpropanoyl-CoA + CO2 + NADH + H+
-
ir
3-methyl-2-oxopentanoate + CoA + NAD+
-
Rattus norvegicus 2-methylbutanoyl-CoA + CO2 + NADH + H+
-
ir
3-methyl-2-oxopentanoate + CoA + NAD+
-
Homo sapiens 2-methylbutanoyl-CoA + CO2 + NADH + H+
-
ir
4-methyl-2-oxopentanoate + CoA + NAD+
-
Rattus norvegicus 3-methylbutanoyl-CoA + CO2 + NADH + H+
-
ir
4-methyl-2-oxopentanoate + CoA + NAD+
-
Homo sapiens 3-methylbutanoyl-CoA + CO2 + NADH + H+
-
ir

Synonyms

Synonyms Comment Organism
BCKDC
-
Rattus norvegicus
BCKDC
-
Homo sapiens
BCKDHA
-
Homo sapiens
BCKDHB
-
Homo sapiens
branched-chain alpha-keto acid dehydrogenase complex
-
Rattus norvegicus
branched-chain alpha-keto acid dehydrogenase complex
-
Homo sapiens
E1alpha subunit
-
Homo sapiens
E1beta subunit
-
Homo sapiens
More cf. EC 1.2.4.4 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
CoA
-
Rattus norvegicus
CoA
-
Homo sapiens
NAD+
-
Rattus norvegicus
NAD+
-
Homo sapiens

General Information

General Information Comment Organism
malfunction maple syrup urine disease (MSUD) results from one or more functional mutations in the E1alpha or E1beta subunit proteins of E1 enzyme or E2 enzyme protein of BCKDC Rattus norvegicus
malfunction maple syrup urine disease (MSUD) results from one or more functional mutations in the E1alpha or E1beta subunit proteins of E1 enzyme or E2 enzyme protein of BCKDC, phenotype, overview Homo sapiens
metabolism the initial step in the catabolism of BCAAs is reversible transamination of Leu, Ile, and Val with alpha-oxoglutarate to produce their respective branched-chain alpha-oxo acids (BCKAs), alpha-oxoisocaproate, 2-oxo-beta-methylvalerate, and 2-oxoisovalerate (KIC, KMV, and KIV, respectively) and Glu via the branched-chain aminotransferase (BCAT) isozymes. The second step is the oxidative decarboxylation of the BCKAs to produce their respective branched-chain acyl-CoA derivatives by the BCKDC. Oxidative decarboxylation of the BCKAs is highly regulated, because it commits the carbon skeleton of these amino acids to irreversible catabolism, which permits net transfer of BCAA nitrogen to Glu. BCAA catabolic pathway, overview. Mitochondrial BCATm, but not cytosolic BCATc, binds and forms a metabolon with GDH or BCKDC Rattus norvegicus
metabolism the initial step in the catabolism of BCAAs is reversible transamination of Leu, Ile, and Val with alpha-oxoglutarate to produce their respective branched-chain alpha-oxo acids (BCKAs), alpha-oxoisocaproate, 2-oxo-beta-methylvalerate, and 2-oxoisovalerate (KIC, KMV, and KIV, respectively) and Glu via the branched-chain aminotransferase (BCAT) isozymes. The second step is the oxidative decarboxylation of the BCKAs to produce their respective branched-chain acyl-CoA derivatives by the BCKDC. Oxidative decarboxylation of the BCKAs is highly regulated, because it commits the carbon skeleton of these amino acids to irreversible catabolism, which permits net transfer of BCAA nitrogen to Glu. BCAA catabolic pathway, overview. Mitochondrial BCATm, but not cytosolic BCATc, binds and forms a metabolon with GDH or BCKDC Homo sapiens
physiological function branched-chain amino acids are key nitrogen donors involved in interorgan and intercellular nitrogen shuttling, and Leu is an important nutrient signal. Unlike most other essential amino acids, BCAAs are initially transaminated in extrahepatic tissues via the branched-chain aminotransferases (BCAT) isozymes, followed by irreversible oxidative decarboxylation of the 2-oxo acid products, catalyzed by the branched-chain 2-oxo acid dehydrogenase enzyme complex (BCKDC), where liver is thought to be a primary site of oxidation. The BCKDC consists of multiple copies of three enzymes: (1) branched-chain 2-oxo acid dehydrogenase (E1-12 copies), (2) dihydrolipoyl transacylase (E2-24 copies), and (3) dihydrolipoyl dehydrogenase (E3-6 copies). The latter is common to all three dehydrogenase complexes. BCKDC activity is controlled via its phosphorylation state of the E1 subunits, with the phosphorylated form rendering the complex inactive. The interorgan/tissue shuttling of BCKA (and other metabolites) for complete oxidation allows for nitrogen transfer and oxidation to occur in different tissues or cells within a tissue, depending on their need for energy, metabolites, or amino acids Rattus norvegicus
physiological function branched-chain amino acids are key nitrogen donors involved in interorgan and intercellular nitrogen shuttling, and Leu is an important nutrient signal. Unlike most other essential amino acids, BCAAs are initially transaminated in extrahepatic tissues via the branched-chain aminotransferases (BCAT) isozymes, followed by irreversible oxidative decarboxylation of the 2-oxo acid products, catalyzed by the branched-chain 2-oxo acid dehydrogenase enzyme complex (BCKDC), where liver is thought to be a primary site of oxidation. The BCKDC consists of multiple copies of three enzymes: (1) branched-chain 2-oxo acid dehydrogenase (E1-12 copies), (2) dihydrolipoyl transacylase (E2-24 copies), and (3) dihydrolipoyl dehydrogenase (E3-6 copies). The latter is common to all three dehydrogenase complexes. BCKDC activity is controlled via its phosphorylation state of the E1 subunits, with the phosphorylated form rendering the complex inactive. The interorgan/tissue shuttling of BCKA (and other metabolites) for complete oxidation allows for nitrogen transfer and oxidation to occur in different tissues or cells within a tissue, depending on their need for energy, metabolites, or amino acids Homo sapiens