A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10483328" target="_blank" >RIV/00216208:11110/24:10483328 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/24:10483328
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=J1ZHjO198v" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=J1ZHjO198v</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cell.2024.04.041" target="_blank" >10.1016/j.cell.2024.04.041</a>
Alternative languages
Result language
angličtina
Original language name
A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis
Original language description
Dolichol is a lipid critical for N-glycosylation as a carrier for activated sugars and nascent oligosaccharides. It is commonly thought to be directly produced from polyprenol by the enzyme SRD5A3. Instead, we found that dolichol synthesis requires a three-step detour involving additional metabolites, where SRD5A3 catalyzes only the second reaction. The first and third steps are performed by DHRSX, whose gene resides on the pseudoautosomal regions of the X and Y chromosomes. Accordingly, we report a pseudoautosomal-recessive disease presenting as a congenital disorder of glycosylation in patients with missense variants in DHRSX (DHRSX-CDG). Of note, DHRSX has a unique dual substrate and cofactor specificity, allowing it to act as a NAD +-dependent dehydrogenase and as a NADPH-dependent reductase in two non-consecutive steps. Thus, our work reveals unexpected complexity in the terminal steps of dolichol biosynthesis. Furthermore, we provide insights into the mechanism by which dolichol metabolism defects contribute to disease.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30100 - Basic medicine
Result continuities
Project
<a href="/en/project/NU22-07-00474" target="_blank" >NU22-07-00474: Molecular genetic causes and biochemical consequences of Congenital disorders of glycosylation</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell
ISSN
0092-8674
e-ISSN
1097-4172
Volume of the periodical
187
Issue of the periodical within the volume
14
Country of publishing house
US - UNITED STATES
Number of pages
40
Pages from-to
3585-"3601.e22"
UT code for WoS article
001272252900001
EID of the result in the Scopus database
2-s2.0-85195665598