A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis.

ABSTRACT: 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-dep

SUBMITTER: Wilson MP 

PROVIDER: S-EPMC11250103 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature