The lysine degradation pathway: Subcellular compartmentalization and enzyme deficiencies.
Amino Acid Metabolism, Inborn Errors
/ genetics
Brain Diseases, Metabolic
/ genetics
Cytosol
/ metabolism
Epilepsy
/ genetics
Glutaryl-CoA Dehydrogenase
/ deficiency
Humans
Lysine
/ analogs & derivatives
Metabolic Networks and Pathways
/ genetics
Mitochondria
/ genetics
Organ Specificity
/ genetics
Peroxisomes
/ genetics
Inborn errors
Lysine degradation
Mitochondria
Pipecolic acid pathway
Saccharopine pathway
Substrate reduction therapy
Journal
Molecular genetics and metabolism
ISSN: 1096-7206
Titre abrégé: Mol Genet Metab
Pays: United States
ID NLM: 9805456
Informations de publication
Date de publication:
Historique:
received:
03
06
2020
revised:
24
07
2020
accepted:
25
07
2020
pubmed:
10
8
2020
medline:
1
7
2021
entrez:
10
8
2020
Statut:
ppublish
Résumé
Lysine degradation via formation of saccharopine is a pathway confined to the mitochondria. The second pathway for lysine degradation, the pipecolic acid pathway, is not yet fully elucidated and known enzymes are localized in the mitochondria, cytosol and peroxisome. The tissue-specific roles of these two pathways are still under investigation. The lysine degradation pathway is clinically relevant due to the occurrence of two severe neurometabolic disorders, pyridoxine-dependent epilepsy (PDE) and glutaric aciduria type 1 (GA1). The existence of three other disorders affecting lysine degradation without apparent clinical consequences opens up the possibility to find alternative therapeutic strategies for PDE and GA1 through pathway modulation. A better understanding of the mechanisms, compartmentalization and interplay between the different enzymes and metabolites involved in lysine degradation is of utmost importance.
Identifiants
pubmed: 32768327
pii: S1096-7192(20)30179-7
doi: 10.1016/j.ymgme.2020.07.010
pii:
doi:
Substances chimiques
Glutaryl-CoA Dehydrogenase
EC 1.3.8.6
Lysine
K3Z4F929H6
saccharopine
WBQ73O8W32
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
14-22Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.