Defective CYP27A1 does not 27-hydroxylate 5β-CHOL3α,7α,24(s)-triol

Stable Identifier
R-HSA-9035960
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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CYP27A1, a mitochondrial matrix sterol hydroxylase, catalyses the 27-hydroxylation of side-chains of sterol intermediates (Cali et al. 1991). In the bile acid synthesis pathway, CYP27A1 catalyses the first step in the oxidation of the side chain of sterol intermediates such as 5β-cholestan-3α, 7α, 24(s)-triol (5β-CHOL3α, 7α, 24(s)-triol) (Pikuleva et al. 1998). Defects in CYP27A1 can cause Cerebrotendinous xanthomatosis (CTX; MIM:213700), a rare sterol storage disorder characterised by progressive neurologic dysfunction, premature atherosclerosis and cataracts (Cali et al. 1991b). Mutations that have a relatively high frequency in some ethnic groups are T339M (Dutch) (Guyant-Marechal et al. 2005), R474(Q-W) (Japanese) (Kim et al. 1994) and A216P (Italian) (Garuti et al. 1996).

Literature References
PubMed ID Title Journal Year
9660774 Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways

Pikuleva, IA, Babiker, A, Waterman, MR, Bjorkhem, I

J Biol Chem 1998
7915755 Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX)

Kim, KS, Kubota, S, Kuriyama, M, Fujiyama, J, Björkhem, I, Eggertsen, G, Seyama, Y

J. Lipid Res. 1994
8827518 Cerebrotendinous xanthomatosis caused by two new mutations of the sterol-27-hydroxylase gene that disrupt mRNA splicing

Garuti, R, Lelli, N, Barozzini, M, Tiozzo, R, Dotti, MT, Federico, A, Ottomano, AM, Croce, A, Bertolini, S, Calandra, S

J. Lipid Res. 1996
1708392 Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis.

Cali, JJ, Russell, DW

J Biol Chem 1991
16278884 Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype

Guyant-Maréchal, L, Verrips, A, Girard, C, Wevers, RA, Zijlstra, F, Sistermans, E, Vera, P, Campion, D, Hannequin, D

Am. J. Med. Genet. A 2005
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
steroid hydroxylase activity of CYP27A1 mutants [mitochondrial matrix]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
cerebrotendinous xanthomatosis 4810 cerebrotendinous xanthomatosis, Cholestanol storage disease (disorder)
Authored
Reviewed
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