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Flux analysis of inborn errors of metabolism
#MMPMID29318410
Reijngoud DJ
J Inherit Metab Dis
2018[May]; 41
(3
): 309-328
PMID29318410
show ga
Patients with an inborn error of metabolism (IEM) are deficient of an enzyme
involved in metabolism, and as a consequence metabolism reprograms itself to
reach a new steady state. This new steady state underlies the clinical phenotype
associated with the deficiency. Hence, we need to know the flux of metabolites
through the different metabolic pathways in this new steady state of the
reprogrammed metabolism. Stable isotope technology is best suited to study this.
In this review the progress made in characterizing the altered metabolism will be
presented. Studies done in patients to estimate the residual flux through the
metabolic pathway affected by enzyme deficiencies will be discussed. After this,
studies done in model systems will be reviewed. The focus will be on glycogen
storage disease type I, medium-chain acyl-CoA dehydrogenase deficiency, propionic
and methylmalonic aciduria, urea cycle defects, phenylketonuria, and combined
D,L-2-hydroxyglutaric aciduria. Finally, new developments are discussed, which
allow the tracing of metabolic reprogramming in IEM on a genome-wide scale. In
conclusion, the outlook for flux analysis of metabolic derangement in IEMs looks
promising.
|Animals
[MESH]
|Humans
[MESH]
|Metabolic Networks and Pathways/*physiology
[MESH]
free
free
free
