Leucine, isoleucine and valine metabolism (WP4686)

Homo sapiens

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This pathway shows disorders related to leucine, isoleusine and valine metabolism. These three substrates are part of a group of chemicals called Branched-chain amino acids (BCAAs), which are essential nutrients and can be found in meat, dairy, and legumes. BCAAs stimulate the building of protein in muscle and possibly reduce muscle breakdown. 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)).

For a description of pathway objects, see the WikiPathways Legend.

Authors

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

Activity

last edited

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Organisms

Homo sapiens

Communities

Inherited Metabolic Disorders (IMD) Pathways Rare Diseases

Annotations

Pathway Ontology

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

Disease Ontology

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

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
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.
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-Methylcrotonylglycine Metabolite chebi:68499
3-Methylglutaconate Metabolite chebi:133513
3-Methylglutarylcarnitine Metabolite chebi:70857
3-Methylglutarate Metabolite chemspider:11781
3-Hydroxy-3-methylglutarate Metabolite chebi:30920
3-Hydroxyhexanoyl-carnitine Metabolite pubchem.compound:131770386
Ketone Bodies Metabolite chebi:73693
Ethylmalonic acid Metabolite chebi:741548
Methylmalonic acid Metabolite chebi:30860
Malonylcarnitine Metabolite chebi:73028
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
2-Methylacetoacetic acid Metabolite chebi:37079
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
3-Aminoisobutyric acid Metabolite chebi:27389
3-Hydroxypropionic acid Metabolite chebi:33404
Beta-alanine Metabolite chebi:16958
3-Hydroxypropionate Metabolite chebi:16510
Propionylglycine Metabolite chebi:89836
Propionylcarnitine Metabolite chebi:28867
R,S-Methylcitrate Metabolite chebi:10860 aka (2R,3S)-2-methylcitrate(3−)
Methylmalonylcarnitine Metabolite chebi:73031
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.
MCC alpha Protein uniprot:Q9HCC0
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