KEGG   ENZYME: 1.14.13.98Help
Entry
EC 1.14.13.98               Enzyme                                 
Name
cholesterol 24-hydroxylase;
cholesterol 24-monooxygenase;
CYP46;
CYP46A1;
cholesterol 24S-hydroxylase;
cytochrome P450 46A1
Class
Oxidoreductases;
Acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
cholesterol,NADPH:oxygen oxidoreductase (24-hydroxylating)
Reaction(IUBMB)
cholesterol + NADPH + H+ + O2 = (24S)-24-hydroxycholesterol + NADP+ + H2O [RN:R07207]
Reaction(KEGG)
Substrate
cholesterol [CPD:C00187];
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007]
Product
(24S)-24-hydroxycholesterol [CPD:C13550];
NADP+ [CPD:C00006];
H2O [CPD:C00001]
Comment
A heme-thiolate protein (P-450). The enzyme can also produce 25-hydroxycholesterol. In addition, it can further hydroxylate the product to 24,25-dihydroxycholesterol and 24,27-dihydroxycholesterol [2]. This reaction is the first step in the enzymatic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood---brain barrier whereas cholesterol cannot [3].
Pathway
Primary bile acid biosynthesis
Orthology
K07440  
cytochrome P450, family 46, subfamily A (cholesterol 24(S)-hydroxylase)
Genes
HSA: 
10858(CYP46A1)
PTR: 
453154(CYP46A1)
PPS: 
GGO: 
PON: 
MCC: 
MMU: 
13116(Cyp46a1)
RNO: 
362782(Cyp46a1)
CFA: 
480432(CYP46A1)
AML: 
FCA: 
101093112
BTA: 
506438(CYP46A1)
SSC: 
100512793
ECB: 
100051131
SHR: 
100926883
OAA: 
100082015
GGA: 
423450(CYP46A1)
MGP: 
100546708
TGU: 
100221970
ACS: 
100552607
XLA: 
100126648 379470(cyp46a1)
XTR: 
100498621 613109 780005(cyp46a1)
DRE: 
553543(cyp46a1)
TRU: 
101077010
OLA: 
101165021 101165274
BFO: 
BRAFLDRAFT_125530
SPU: 
575475
NVE: 
NEMVE_v1g101023
 » show all
Taxonomy
Reference
1  [PMID:10377398]
  Authors
Lund EG, Guileyardo JM, Russell DW.
  Title
cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 7238-43.
  Organism
Mus musculus [GN:mmu]
Reference
2  [PMID:14640697]
  Authors
Mast N, Norcross R, Andersson U, Shou M, Nakayama K, Bjorkhem I, Pikuleva IA.
  Title
Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.
  Journal
Biochemistry. 42 (2003) 14284-92.
  Organism
Homo sapiens [GN:hsa]
Reference
3  [PMID:12686551]
  Authors
Lund EG, Xie C, Kotti T, Turley SD, Dietschy JM, Russell DW.
  Title
Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover.
  Journal
J. Biol. Chem. 278 (2003) 22980-8.
  Organism
Homo sapiens [GN:hsa], Mus musculus [GN:mmu]
Reference
4  [PMID:11698143]
  Authors
Bogdanovic N, Bretillon L, Lund EG, Diczfalusy U, Lannfelt L, Winblad B, Russell DW, Bjorkhem I.
  Title
On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells.
  Journal
Neurosci. Lett. 314 (2001) 45-8.
  Organism
Homo sapiens [GN:hsa]
Reference
5  [PMID:12543708]
  Authors
Russell DW.
  Title
The enzymes, regulation, and genetics of bile acid synthesis.
  Journal
Annu. Rev. Biochem. 72 (2003) 137-74.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
50812-30-1 213327-78-7
DBGET integrated database retrieval system