Cerebral organic acidurias, including diseases (WP4519)

This pathway shows disorders related to the accumulation of organic acids in body fluids, resulting in cerebral organic acidurias. Symptoms often include mental or motor retardation, difficulties while moving and epilepsy. For all but one disorder, current treatment options have been proven ineffective. Disorders resulting from an enzyme defect are highlighted in pink. This pathway was inspired by Chapter 8 of the book of Blau (ISBN 3642403360 (978-3642403361)).
last edited

Authors

BrittPieters, DeSl, EviSchoenmaker, IreneHemel, Egonw, MaintBot, Fehrhart, Eweitz, and Finterly

Cited In

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Organism

Homo sapiens

Communities

Inborn Errors of Metabolism (IEM) Pathways Rare Diseases

Annotations

Disease Ontology: Canavan disease organic acidemia 2-hydroxyglutaric aciduria D-2-hydroxyglutaric aciduria

Pathway Ontology: lysine degradation pathway glutaric aciduria type I pathway disease pathway

Participants

Label Type Compact Identifier
hydroxylysine Metabolite chebi:60175
Antiquitin Protein ensembl:ENSG00000164904
Tryptophan Metabolite chebi:16828
Glutaric acid Metabolite chebi:17859
Glutaconyl coenzyme A Metabolite pubchem.compound:9543050
3-Hydroxyglutaric acid Metabolite hmdb:HMDB0000428
FAD Metabolite chebi:16238
TCA cycle Pathway wikipathways:WP78
NADPH Metabolite chebi:16474
IDH2 Protein ensembl:ENSG00000182054
D-2-hydroxyglutarate dehydrogenase Protein uniprot:B5MCV2
Acetyl coenzyme A Metabolite chebi:15351
glutaryl-coenzyme A Metabolite chebi:15524
L-2-Aminoadipic acid Metabolite chebi:37024
FADH2 Metabolite chebi:17877
Glutaconic acid Metabolite chebi:24309
NADPH+ Metabolite hmdb:HMDB0000221
L-2-Hydroxyglutaric acid Metabolite hmdb:HMDB0000694
NADH Metabolite chebi:16908
2-Oxoadipic acid Metabolite chebi:15753
L2HGDH Protein ensembl:ENSG00000087299
L-N-Acetylaspartate Metabolite chebi:21547
H+ Metabolite chebi:15378
L-malDH Protein uniprot:A0A024R4K3
Saccharopine pathway Pathway wikipathways:WP4228
Hydroxyacid-oxoacid transhydrogenase Protein uniprot:B4DFI7
Aspartate Metabolite chebi:17053
Glutaryl-Coenzyme A dehydrogenase Protein uniprot:A0A024R7F9
Coenzyme A Metabolite chebi:15346
lysine Metabolite chebi:25094
2-Ketoglutaric acid Metabolite chebi:30915
Aminoacylase-2 Protein uniprot:A0A1B0GTG3
CROTONYL COENZYME A Metabolite chebi:15473
NAD+ Metabolite chebi:15846
D-2-Hydroxyglutaric acid Metabolite hmdb:HMDB0000606
Pipecolic acid pathway Pathway wikipathways:WP4228
2-aminoadipic semialdehyde Metabolite chebi:61515
Aspartate Metabolite chebi:17053
H+ Metabolite chebi:15378
Acetyl coenzyme A Metabolite chebi:15351
glutarylcarnitine Metabolite chebi:73040
3-hydroxyglutaryl coenzyme a Metabolite pubchem.compound:445127
Glutaryl-Coenzyme A dehydrogenase Protein uniprot:A0A024R7F9

References

  1. Kvittingen EA, Guldal G, Børsting S, Skalpe IO, Stokke O, Jellum E. N-acetylaspartic aciduria in a child with a progressive cerebral atrophy. Clin Chim Acta. 1986 Aug 15;158(3):217–27. PubMed Europe PMC Scholia
  2. Chalmers RA, Lawson AM, Watts RW, Tavill AS, Kamerling JP, Hey E, et al. D-2-hydroxyglutaric aciduria: case report and biochemical studies. J Inherit Metab Dis. 1980;3(1):11–5. PubMed Europe PMC Scholia
  3. Hoffmann GF, Böhles HJ, Burlina A, Duran M, Herwig J, Lehnert W, et al. Early signs and course of disease of glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 1995;18(2):173–6. PubMed Europe PMC Scholia
  4. BANKER BQ, ROBERTSON JT, VICTOR M. SPONGY DEGENERATION OF THE CENTRAL NERVOUS SYSTEM IN INFANCY. Neurology. 1964 Nov;14:981–1001. PubMed Europe PMC Scholia
  5. Rzem R, Van Schaftingen E, Veiga-da-Cunha M. The gene mutated in l-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase. Biochimie. 2006 Jan;88(1):113–6. PubMed Europe PMC Scholia
  6. Hedlund GL, Longo N, Pasquali M. Glutaric acidemia type 1. Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):86–94. PubMed Europe PMC Scholia
  7. Arun P, Moffett JR, Namboodiri AMA. Evidence for mitochondrial and cytoplasmic N-acetylaspartate synthesis in SH-SY5Y neuroblastoma cells. Neurochem Int. 2009 Sep;55(4):219–25. PubMed Europe PMC Scholia
  8. Kranendijk M, Struys EA, van Schaftingen E, Gibson KM, Kanhai WA, van der Knaap MS, et al. IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. Science. 2010 Oct 15;330(6002):336. PubMed Europe PMC Scholia
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