The Metabolic Map into the Pathomechanism and Treatment of PGM1-CDG
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F19%3A10399148" target="_blank" >RIV/00064165:_____/19:10399148 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/19:10399148
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=qoK-UFTDmL" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=qoK-UFTDmL</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ajhg.2019.03.003" target="_blank" >10.1016/j.ajhg.2019.03.003</a>
Alternative languages
Result language
angličtina
Original language name
The Metabolic Map into the Pathomechanism and Treatment of PGM1-CDG
Original language description
Phosphoglucomutase 1 (PGM1) encodes the metabolic enzyme that interconverts glucose-6-P and glucose-1-P. Mutations in PGM1 cause impairment in glycogen metabolism and glycosylation, the latter manifesting as a congenital disorder of glycosylation (CDG). This unique metabolic defect leads to abnormal N-glycan synthesis in the endoplasmic reticulum (ER) and the Golgi apparatus (GA). On the basis of the decreased galactosylation in glycan chains, galactose was administered to individuals with PGM1-CDG and was shown to markedly reverse most disease-related laboratory abnormalities. The disease and treatment mechanisms, however, have remained largely elusive. Here, we confirm the clinical benefit of galactose supplementation in PGM1-CDG-affected individuals and obtain significant insights into the functional and biochemical regulation of glycosylation. We report here that, by using tracer-based metabolomics, we found that galactose treatment of PGM1-CDG fibroblasts metabolically re-wires their sugar metabolism, and as such replenishes the depleted levels of galactose-1-P, as well as the levels of UDP-glucose and UDP-galactose, the nucleotide sugars that are required for ER- and GA-linked glycosylation, respectively. To this end, we further show that the galactose in UDP-galactose is incorporated into mature, de novo glycans. Our results also allude to the potential of monosaccharide therapy for several other CDG.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10600 - Biological sciences
Result continuities
Project
<a href="/en/project/NV16-31932A" target="_blank" >NV16-31932A: Molecular mechanisms of congenital disorders of glycosylation</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
The American Journal of Human Genetics
ISSN
0002-9297
e-ISSN
—
Volume of the periodical
104
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
835-846
UT code for WoS article
000466608700005
EID of the result in the Scopus database
2-s2.0-85064951105