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Inborn disorders of the malate aspartate shuttle
- Source :
- Journal of Inherited Metabolic Disease
- Publication Year :
- 2021
-
Abstract
- Over the last few years, various inborn disorders have been reported in the malate aspartate shuttle (MAS). The MAS consists of 4 metabolic enzymes and 2 transporters, one of them having two isoforms that are expressed in different tissues. Together they form a biochemical pathway that shuttles electrons from the cytosol into mitochondria, as the inner mitochondrial membrane is impermeable to the electron carrier NADH. By shuttling NADH across the mitochondrial membrane in the form of a reduced metabolite (malate), the MAS plays an important role in mitochondrial respiration. In addition, the MAS maintains the cytosolic NAD+ /NADH redox balance, by using redox reactions for the transfer of electrons. This explains why the MAS is also important in sustaining cytosolic redox-dependent metabolic pathways, such as glycolysis and serine biosynthesis. The current review provides insights into the clinical and biochemical characteristics of MAS deficiencies. To date, 5 out of 7 potential MAS deficiencies have been reported. Most of them present with a clinical phenotype of infantile epileptic encephalopathy. Although not specific, biochemical characteristics include high lactate, high glycerol 3-phosphate, a disturbed redox balance, TCA abnormalities, high ammonia and low serine, which may be helpful in reaching a diagnosis in patients with an infantile epileptic encephalopathy. Current implications for treatment include a ketogenic diet, as well as serine and vitamin B6 supplementation. This article is protected by copyright. All rights reserved.
- Subjects :
- Cell Respiration
Malates
Malate-aspartate shuttle
Review Article
Mitochondrion
GOT2
AGC1
AGC2
malate aspartate shuttle
Serine
inborn metabolic disorder
Malate Dehydrogenase
Genetics
Animals
Humans
Glycolysis
Aspartate Aminotransferases
Inner mitochondrial membrane
Review Articles
Genetics (clinical)
Aspartic Acid
Chemistry
NAD(H)
Infant
Mitochondria
Metabolic pathway
Biochemistry
redox
lipids (amino acids, peptides, and proteins)
NAD+ kinase
MDH2
Spasms, Infantile
Metabolism, Inborn Errors
MDH1
Subjects
Details
- ISSN :
- 15732665
- Volume :
- 44
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of inherited metabolic disease
- Accession number :
- edsair.doi.dedup.....20454fda26e7149cef981f0ce36e1980