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 incorporation or reduction of molecular oxygen;
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 enzymic degradation of cholesterol in the brain as hydroxycholesterol can pass the blood---brain barrier whereas cholesterol cannot [3].
History
EC 1.14.13.98 created 2005
Pathway
Primary bile acid biosynthesis
Orthology
K07440  
cholesterol 24(S)-hydroxylase
Genes
HSA: 
10858(CYP46A1)
PTR: 
453154(CYP46A1)
PPS: 
GGO: 
PON: 
MCC: 
MCF: 
MMU: 
13116(Cyp46a1)
RNO: 
362782(Cyp46a1)
CGE: 
HGL: 
TUP: 
CFA: 
480432(CYP46A1)
AML: 
FCA: 
PTG: 
BTA: 
506438(CYP46A1)
BOM: 
PHD: 
CHX: 
OAS: 
SSC: 
CFR: 
BACU: 
LVE: 
ECB: 
MYB: 
MYD: 
PALE: 
SHR: 
OAA: 
GGA: 
423450(CYP46A1)
MGP: 
TGU: 
FAB: 
PHI: 
APLA: 
FPG: 
FCH: 
CLV: 
ASN: 
AMJ: 
PSS: 
CMY: 
ACS: 
PBI: 
XLA: 
100126648 379470(cyp46a1)
XTR: 
DRE: 
393433(cyp46a1.2) 393451(cyp46a1.4) 553543(cyp46a1.1) 641477 692332(cyp46a1.3)
TRU: 
MZE: 
OLA: 
XMA: 
LCM: 
CMK: 
BFO: 
SPU: 
NVE: 
FME: 
 » 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.
  Sequence
[mmu:13116] [hsa:10858]
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.
  Sequence
[hsa:10858]
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.
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.
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

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