Defective DHDDS does not elongate E,E-FPP

Stable Identifier
Reaction [transition]
Homo sapiens
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The ER membrane-associated enzyme dehydrodolichyl diphosphate synthase (DHDDS) (Endo et al. 2003) normally mediates the sequential head-to-tail cis addition of multiple isopentyl pyrophosphate (IPP) molecules to farnesyl pyrophosphate (E,E-FPP) to produce polyprenol pyrophosphate (pPPP) (Shridas et al. 2003). Dolichol in humans contain homologues ranging from 17-23 isoprene units, the most common homologues contain 19 or 20 isoprene units (Freeman et al. 1980). Dolichol is an important substrate in the N-glycosylation of proteins, including rhodopsin.

Defects in DHDDS cause retinitis pigmentosa 59 (RP59; MIM:613861), a pigment retinopathy, characterised by retinal pigment deposits (visible on fundus examination) and primary loss of rod photoreceptors followed by secondary loss of cone photoreceptors. Sufferers typically have night vision blindness and loss of mid to peripheral vision. As the condition progresses, they lose far peripheral vision and eventually central vision (Zuchner et al. 2011). The founder missense mutation K42E in Ashkenazi Jewish ethnicity can cause RP59. The Lys42 residue is highly conserved across different species and is positioned close to the catalytic centre of DHDDS and to its substrate binding site for E,E-FPP (Zuchner et al. 2011, Zelinger et al. 2011).

Literature References
PubMed ID Title Journal Year
7374371 Analysis of dolichol in human tissues by high pressure liquid chromatography

Rupar, CA, Carroll, KK, Freeman, DJ

Lipids 1980
21295282 A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews

Merin, S, Jacobson, SG, Frenkel, S, Banin, E, Schwartz, SB, Obolensky, A, Zelinger, L, Sharon, D, Bandah-Rozenfeld, D, Beryozkin, A, Cideciyan, AV, Mizrahi-Meissonnier, L, Ben-Yosef, T

Am. J. Hum. Genet. 2011
21295283 Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa

Z├╝chner, S, Buxbaum, JD, Wen, R, Vance, JM, Farooq, A, Pericak-Vance, MA, Haines, JL, Blanton, S, Peter, I, Edwards, YJ, Cai, G, Hulme, W, Dallman, J, Alfonso, E, Young, J, Naj, A, Seo, D, Lam, BL, Beecham, G, Kohli, MA, Whitehead, PL, Konidari, I

Am. J. Hum. Genet. 2011
14652022 Identification and characterization of a cDNA encoding a long-chain cis-isoprenyltranferase involved in dolichyl monophosphate biosynthesis in the ER of brain cells

Shridas, P, Waechter, CJ, Rush, JS

Biochem. Biophys. Res. Commun. 2003
12591616 Identification of human dehydrodolichyl diphosphate synthase gene

Zhang, YW, Koyama, T, Takahashi, S, Endo, S

Biochim. Biophys. Acta 2003
Catalyst Activity

transferase activity, transferring alkyl or aryl (other than methyl) groups of DHDDS K42E:NUS1 [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of DHDDS K42E:NUS1 [endoplasmic reticulum membrane]

Name Identifier Synonyms
retinitis pigmentosa DOID:10584 RP, Retinitis pigmentosa (disorder), retinitis pigmentosa-1, Retinitis pigmentosa, Retinitis pigmentosa
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