Reactome | SRD5A3 reduces polyprenal to dolichal

SRD5A3 reduces polyprenal to dolichal

Stable Identifier

R-HSA-9937295

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytoplasmic side of endoplasmic reticulum membrane, cytosol, endoplasmic reticulum membrane

Synonyms

a di-trans,poly-cis-polyprenal + NADPH + H(+) => a di-trans,poly-cis-dolichal + NADP(+)

ReviewStatus

5/5

Locations in the PathwayBrowser

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Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Asparagine N-linked glycosylation (Homo sapiens)
    - Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (Homo sapiens)
      - Synthesis of substrates in N-glycan biosythesis (Homo sapiens)
        
        Synthesis of dolichyl-phosphate (Homo sapiens)
        
        SRD5A3 reduces polyprenal to dolichal (Homo sapiens)

General

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SRD5A3 (Polyprenal reductase) associated with the cytoplasmic face of the ER membrane, catalyzes the reduction of polyprenal (pPNAL) to dolichal (DCHAL) coupled to the oxidation of NADPH + H+ to NADP+ (Wilson et al. 2024).

Defects in SRD5A3 cause congenital disorder of glycosylation 1q (SRD5A3-CDG, CDG1Q; MIM:612379), a neurodevelopmental disorder characterised by under-glycosylated serum glycoproteins resulting in nervous system development, psychomotor retardation, hypotonia, coagulation disorders and immunodeficiency (Cantagrel et al. 2010, Kasapkara et al. 2012). Defects in SRD5A3 can also cause Kahrizi syndrome (KHRZ; MIM:612713), a neurodevelopmental disorder characterised by mental retardation, cataracts, coloboma, kyphosis, and coarse facial features (Kahrizi et al. 2011).

Literature References

PubMed ID	Title	Journal	Year
38821050	A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis Wilson, MP, Kentache, T, Althoff, CR, Schulz, C, de Bettignies, G, Mateu Cabrera, G, Cimbalistiene, L, Burnyte, B, Yoon, G, Costain, G, Vuillaumier-Barrot, S, Cheillan, D, Rymen, D, Rychtarova, L, Hansikova, H, Bury, M, Dewulf, JP, Caligiore, F, Jaeken, J, Cantagrel, V, Van Schaftingen, E, Matthijs, G, Foulquier, F, Bommer, GT	Cell	2024
20700148	Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3 Kahrizi, K, Hu, CH, Garshasbi, M, Abedini, SS, Ghadami, S, Kariminejad, R, Ullmann, R, Chen, W, Ropers, HH, Kuss, AW, Najmabadi, H, Tzschach, A	Eur. J. Hum. Genet.	2011
20637498	SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder Cantagrel, V, Lefeber, DJ, Ng, BG, Guan, Z, Silhavy, JL, Bielas, SL, Lehle, L, Hombauer, H, Adamowicz, M, Swiezewska, E, De Brouwer, AP, Blümel, P, Sykut-Cegielska, J, Houliston, S, Swistun, D, Ali, BR, Dobyns, WB, Babovic-Vuksanovic, D, van Bokhoven, H, Wevers, RA, Raetz, CR, Freeze, HH, Morava, E, Al-Gazali, L, Gleeson, JG	Cell	2010
22240719	SRD5A3-CDG: a patient with a novel mutation Kasapkara, CS, Tümer, L, Ezgü, FS, Hasanoğlu, A, Race, V, Matthijs, G, Jaeken, J	Eur. J. Paediatr. Neurol.	2012