Leucine, isoleucine and valine metabolism (WP4686)

Homo sapiens

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This pathway shows disorders related to leucine, isoleusine and valine metabolism. Disorders resulting from an enzyme defect are highlighted in pink. This pathway was inspired by Chapter 7 of the book of Blau (ISBN 3642403360 (978-3642403361)).

Authors

Amy Kutmon , Denise Slenter , Lauren J. Dupuis , Eric Weitz , Finterly Hu , and Sam Drabbe

Activity

last edited

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Organisms

Homo sapiens

Communities

Inherited Metabolic Disorders (IMD) Pathways Rare Diseases

Annotations

Disease Ontology

maple syrup urine disease isovaleric acidemia propionic acidemia 3-Methylcrotonyl-CoA carboxylase deficiency methylmalonic acidemia 3-methylglutaconic aciduria type 4 inherited metabolic disorder

Pathway Ontology

leucine metabolic pathway methylmalonic acidemia pathway isovaleric acidemia pathway methylmalonate semialdehyde dehydrogenase deficiency pathway propionic acidemia pathway 3-hydroxy-3-methylglutaryl-CoA lyase deficiency pathway isoleucine metabolic pathway isobutyryl-CoA dehydrogenase deficiency pathway valine metabolic pathway maple syrup urine disease pathway malonic aciduria pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
Methylmalonate Metabolite chebi:17453
alloisoleucine Metabolite chebi:43433 Connection of this metabolite to pathway is unclear, figure in book links this to the protein?)
Assumed to be the L-form, according to [https://en.wikipedia.org/wiki/Isoleucine] Table with isomers, where the synonym of L-alloisoleucine is alloisoleucine.
Biotin Metabolite chebi:15956 'alpha subunit is covalently bound to biotin, which is essential for the ATP-dependent carboxylation'. Source: [https://en.wikipedia.org/wiki/Methylcrotonyl-CoA_carboxylase#Protein]
3-Methylcrotonyl-CoA Metabolite chebi:57344
3-Hydroxybutyrate Metabolite chebi:37054
2-Oxoisovalerate Metabolite chebi:11851
Isobutyrylcarnitine Metabolite chebi:73017
Methylmalonate Metabolite chebi:17453
3-Hydroxy-3-methylglutaryl-CoA Metabolite chebi:43074
Isoleucine Metabolite chebi:24898
3-Hydroxyisobutyrate Metabolite chebi:62638
Malonic acid Metabolite chebi:30794
L-Valine Metabolite chebi:57762
Isobutyrylglycine Metabolite chebi:70979
2-Hydroxyisovalerate Metabolite chebi:64669 aka 2-hydroxy-3-methylbutyrate
S-2-carboxypropylcysteine Metabolite pubchem.compound:129651610 AKA S-2-carboxypropyl-cysteine; annotated based on closest match in PubChem compound (carboxypropyl-cysteine, which doesn't specifiy the location and orientation of the carboxypropyl group).
Malonate Metabolite chebi:15792
Methylmalonyl-CoA Metabolite chebi:57327
3-Hydroxyisobutyrylcarnitine Metabolite pubchem.compound:129692225 aka 3-Hydroxyisobutyryl-carnitine
Acetoacetate Metabolite chebi:13705
2-Methylaceto-acetyl-CoA Metabolite chebi:57335 AKA 2-methyl-3-oxobutanoyl-CoA
2-Methyl-3-hydroxy-butyryl-CoA Metabolite chebi:165613
Valine Metabolite chebi:27266
Tiglyl-CoA Metabolite chebi:15478 AKA 2-methylcrotonoyl-CoA
L-Isoleucine Metabolite chebi:17191
2-Methylbutyryl-CoA Metabolite chebi:57336 AKA 2-methylbutanoyl-CoA
2-Hydroxyisovalerate Metabolite chebi:64669
2-Oxo-3-methylvalerate Metabolite chebi:28654 AKA 3-methyl-2-oxovalerate, a Branched-chain-keto acid (BCKA)
L-Leucine Metabolite chebi:15603
Acetyl-CoA Metabolite chebi:57288
2-Oxoisocaproate Metabolite chebi:17865
S-2-carboxypropylcysteamine Metabolite chebi:184285
Malonyl-CoA Metabolite chebi:15531 Potentially interesting Rhea ID: https://www.rhea-db.org/rhea/18817 , for reaction with malonate and Acetyl-CoA, however no directionality known.
2-Oxoisocaproate Metabolite chebi:17865
Isovaleryl-CoA Metabolite chebi:57345
Methacrylyl-CoA Metabolite chebi:62500 AKA (2E)-2-methylpropenoyl-CoA (Rhea match)
Isobutyryl-CoA Metabolite chebi:15479
2-Oxo-isovalerate Metabolite chebi:11851
Succinyl-CoA Metabolite chebi:57292
Propionyl-CoA Metabolite chebi:57392 AKA propanoyl-CoA in Rhea
Methylmalonate semialdehyde Metabolite chebi:62413
3-Hydroxyisobutyrate Metabolite chebi:62638 AKA (S)-3-hydroxy-2-methylpropanoate in Rhea
3-Hydroxyiso-butyryl-CoA Metabolite chebi:62611
2-Hydroxyisocaproate Metabolite chebi:133577
3-Hydroxyisovalerate Metabolite chebi:82957
Leucine Metabolite chebi:25017
Isovalerylglycine Metabolite chebi:70984
Isovaleryglucuronide Metabolite pubchem.compound:137383
Isovaleric acid Metabolite chebi:28484
4-Hydroxyisovaleric acid Metabolite pubchem.compound:131760
Isovalerylcarnitine Metabolite chebi:73025
3-Hydroxyisovalerate Metabolite chebi:82957
3-Methylcrotonylglycine Metabolite chebi:68499
3-Methylglutaconate Metabolite chebi:133513
3-Methylglutarylcarnitine Metabolite chebi:70857
3-Hydroxyisovalerate Metabolite chebi:82957
3-Methylglutarate Metabolite chemspider:11781
3-Methylglutaconate Metabolite chebi:133513
3-Hydroxyisovalerate Metabolite chebi:82957
3-Methylglutarate Metabolite chemspider:11781
3-Hydroxy-3-methylglutarate Metabolite chebi:30920
3-Methylcrotonylglycine Metabolite chebi:68499
3-Hydroxyhexanoyl-carnitine Metabolite pubchem.compound:131770386
Ketone Bodies Metabolite chebi:73693
Malonic acid Metabolite chebi:30794
Ethylmalonic acid Metabolite chebi:741548
Methylmalonic acid Metabolite chebi:30860
Malonylcarnitine Metabolite chebi:73028
2-Oxo-3-methylvalerate Metabolite chebi:28654 AKA 3-methyl-2-oxovalerate, a Branched-chain-keto acid (BCKA)
2-Methylbutyrylcarnitine Metabolite chebi:73026
2-Hydroxy-3-methylvalerate Metabolite pubchem.compound:10796774 aka 2-hydroxy-3-methylpentanoic acid
2-Methylbutyrylglycine Metabolite chebi:86366 AKA N-(2-methylbutanoyl)glycine
2-Ethylhydracrylic acid Metabolite chebi:82956
Tiglylglycine Metabolite chebi:73018
Tiglylgycine Metabolite chebi:73018
Tiglylglycine Metabolite chebi:73018
2-Methylacetoacetic acid Metabolite chebi:37079
2-Methyl-3-hydroxybutyrate Metabolite chebi:78554
2-Methyl-3-hydroxybutyrate Metabolite chebi:78554
Tiglylcarnitine Metabolite chebi:71179
Tiglycarnitine Metabolite chebi:71179
2-Methyl-3-hydroxybutyryl-carnitine Metabolite pubchem.compound:129663780 aka 2-Methyl-3-hydroxybutyrylcarnitine, 2-Methyl-3-hydroxy-butyrylcarnitine, 2-Methyl-3-hydroxy-butyryl-carnitine, 2-Methyl-3-hydroxybutyryl-carnitine, 2-Methyl-3-hydroxybutyryl carnitine
2-Methyl-3-hydroxy-butyrylcarnitine Metabolite pubchem.compound:129663780 aka 2-Methyl-3-hydroxybutyrylcarnitine, 2-Methyl-3-hydroxy-butyrylcarnitine, 2-Methyl-3-hydroxy-butyryl-carnitine, 2-Methyl-3-hydroxybutyryl-carnitine, 2-Methyl-3-hydroxybutyryl carnitine
2-Hydroxyisovalerate Metabolite chebi:64669
3-Hydroxyisobutyrylcarnitine Metabolite pubchem.compound:129692225 aka 3-Hydroxyisobutyryl-carnitine
3-Aminoisobutyric acid Metabolite chebi:27389
3-Hydroxyisobutyrate Metabolite chebi:62638
3-Hydroxypropionic acid Metabolite chebi:33404
Ethylmalonic acid Metabolite chebi:741548
Beta-alanine Metabolite chebi:16958
3-Hydroxypropionate Metabolite chebi:16510
Propionylglycine Metabolite chebi:89836
Tiglylglycine Metabolite chebi:73018
Propionylcarnitine Metabolite chebi:28867
R,S-Methylcitrate Metabolite chebi:10860 aka (2R,3S)-2-methylcitrate(3−)
R,S-Methylcitrate Metabolite chebi:10860 aka (2R,3S)-2-methylcitrate(3−)
3-Hydroxypropionate Metabolite chebi:16510
Propionylcarnitine Metabolite chebi:28867
Methylmalonylcarnitine Metabolite chebi:73031
Methylmalonic acid Metabolite chebi:30860
Malonylcarnitine Metabolite chebi:73028
3-Methyl-glutaconyl-CoA Metabolite chebi:57346
PCCB Protein uniprot:P05166
E1 (alpha) Protein uniprot:P12694 E1 uses thiamine pyrophosphate (TPP) as a catalytic cofactor.
BCAT1 Protein uniprot:P54687
E2 (aka DBT) Protein uniprot:P11182
Hydratase Protein uniprot:Q13825 AKA Methylglutaconyl-CoA hydratase
MCC alpha Protein uniprot:Q96RQ3 'alpha subunit is covalently bound to biotin, which is essential for the ATP-dependent carboxylation'. Source: [https://en.wikipedia.org/wiki/Methylcrotonyl-CoA_carboxylase#Protein]
IVD Protein uniprot:P26440
Malonyl-CoA decarboxylase Protein uniprot:O95822 AKA MLYCD
ACSF3 Protein uniprot:Q4G176
Aminotransferase Protein eccode:2.6.1.42
MHBD Protein uniprot:Q99714
HMG-CoA lyase Protein uniprot:Q8TB92
ACADSB Protein uniprot:P45954 MBD is abbreviation for disorder, not for the protein/gene
Beta-ketothiolase Protein uniprot:P24752 AKA ACAT1, confirmed with disorder Table from book and link to UniProt from Rhea
E3 (aka DLD) Protein uniprot:P09622
HIBCH Protein uniprot:Q6NVY1
SCEH Protein uniprot:P30084 aka ECHS1, protein confirmed by Rhea and UniProt
IBD Protein uniprot:Q9UKU7
PCCA Protein uniprot:P05165
MMSDH Protein uniprot:Q02252 AKA ALDH6A1
HIBADH Protein uniprot:P31937
Mutase Protein uniprot:P22033 AKA MMUT, confired by Rhea linking to UniProt and Table in book on disorders.
E1 (beta) Protein uniprot:P21953 E1 uses thiamine pyrophosphate (TPP) as a catalytic cofactor.
E2 (aka DBT) Protein uniprot:P11182
E3 (aka DLD) Protein uniprot:P09622
E1 (alpha) Protein uniprot:P12694 E1 uses thiamine pyrophosphate (TPP) as a catalytic cofactor.
E1 (beta) Protein uniprot:P21953 E1 uses thiamine pyrophosphate (TPP) as a catalytic cofactor.
E2 (aka DBT) Protein uniprot:P11182
E3 (aka DLD) Protein uniprot:P09622
E1 (alpha) Protein uniprot:P12694 E1 uses thiamine pyrophosphate (TPP) as a catalytic cofactor.
E1 (beta) Protein uniprot:P21953 E1 uses thiamine pyrophosphate (TPP) as a catalytic cofactor.
MCC alpha Protein uniprot:Q9HCC0
BCAT2 Protein uniprot:O15382
BCAT1 Protein uniprot:P54687
Aminotransferase Protein eccode:2.6.1.42
BCAT2 Protein uniprot:O15382
BCAT1 Protein uniprot:P54687
Aminotransferase Protein eccode:2.6.1.42
BCAT2 Protein uniprot:O15382

References

  1. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Springer; 2014. 0 p. Available from: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
  2. Enoyl-CoA hydratase. reaction, mechanism, and inhibition. Agnihotri G, Liu H wen. Bioorg Med Chem. 2003 Jan 2;11(1):9–20. PubMed Europe PMC Scholia
  3. Expression, purification, characterization of human 3-methylcrotonyl-CoA carboxylase (MCCC). Chu CH, Cheng D. Protein Expr Purif. 2007 Jun;53(2):421–7. PubMed Europe PMC Scholia