KEGG   ENZYME: 1.14.14.25Help
Entry
EC 1.14.14.25               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 reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
Sysname
cholesterol,NADPH---hemoprotein reductase:oxygen oxidoreductase (24-hydroxylating)
Reaction(IUBMB)
cholesterol + [reduced NADPH---hemoprotein reductase] + O2 = (24S)-cholest-5-ene-3beta,24-diol + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R07207]
Reaction(KEGG)
Substrate
cholesterol [CPD:C00187];
[reduced NADPH---hemoprotein reductase] [CPD:C03024];
O2 [CPD:C00007]
Product
(24S)-cholest-5-ene-3beta,24-diol [CPD:C13550];
[oxidized NADPH---hemoprotein reductase] [CPD:C03161];
H2O [CPD:C00001]
Comment
A P-450 heme-thiolate protein. 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]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase [3].
History
EC 1.14.14.25 created 2005 as EC 1.14.13.98, transferred 2016 to EC 1.14.14.25
Pathway
ec00120  Primary bile acid biosynthesis
Orthology
K07440  cholesterol 24-hydroxylase
Genes
HSA: 10858(CYP46A1)
PTR: 453154(CYP46A1)
PPS: 100978372
GGO: 101142101
PON: 100440873
NLE: 100604931
MCC: 705843
MCF: 102140307
CSAB: 103229682(CYP46A1)
RRO: 104654463
RBB: 108519071
CJC: 100403833(CYP46A1)
SBQ: 101048333
MMU: 13116(Cyp46a1)
MCAL: 110306885
MPAH: 110324576
RNO: 362782(Cyp46a1)
MUN: 110566352
CGE: 100769865
NGI: 103727655
HGL: 101708822
CCAN: 109694347
OCU: 100354574
TUP: 102499401
CFA: 480432(CYP46A1)
VVP: 112930232
AML: 100470338
UMR: 103673592
UAH: 113267281
ORO: 101365372
ELK: 111148659
FCA: 101093112
PTG: 102970492
PPAD: 109274544
AJU: 106972183
BTA: 506438(CYP46A1)
BOM: 102270768
BIU: 109575242
BBUB: 102397524
CHX: 102178217
OAS: 101117622
SSC: 100512793
CFR: 102522998
CDK: 105095410
BACU: 103014370
LVE: 103068707
OOR: 101280175
DLE: 111176091
PCAD: 102976598
ECB: 100051131
EPZ: 103550566
EAI: 106839686
MYB: 102251844
MYD: 102761609
MNA: 107542730
HAI: 109381070
DRO: 112311755
PALE: 102898643
RAY: 107518577
MJV: 108394816
LAV: 100677635
TMU: 101353740
PCW: 110222404
OAA: 100082015
GGA: 423450(CYP46A1)
MGP: 100546708
CJO: 107315364
NMEL: 110401402
APLA: 101792317
ACYG: 106036083
TGU: 100221970
LSR: 110481165
SCAN: 103826433
GFR: 102044337
FAB: 101816121
PHI: 102099615
PMAJ: 107206481
CCAE: 111929830
CCW: 104686436
ETL: 114061692
FPG: 101918324
FCH: 102060075
CLV: 102086481
EGZ: 104124527
NNI: 104014834
ACUN: 113480441
PADL: 103920698
AAM: 106482958
ASN: 102376314
AMJ: 102574122(CYP46A1)
PSS: 102449598
CMY: 102937516
CPIC: 101950833
PBI: 103060230
PMUR: 107291347
TSR: 106554955
XLA: 100126648 108704878 379470(cyp46a1.L)
XTR: 100145328 100498621 613109(cyp46a1.3) 613111(cyp46a1.1) 780005(cyp46a1.2)
DRE: 393433(cyp46a1.2) 393451(cyp46a1.4) 553543(cyp46a1.1) 641477(zgc:123299) 692332(cyp46a1.3)
AMEX: 103039880
LCO: 104926956
NCC: 104967646
AOCE: 111578258
POV: 109632307
LCF: 108898059
SDU: 111240402
SLAL: 111672518
HCQ: 109523501
PKI: 111850949
LCM: 102350084
CMK: 103191174
RTP: 109920427
SKO: 102809914
 » 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 96:7238-43 (1999)
DOI:10.1073/pnas.96.13.7238
  Sequence
[hsa:10858] [mmu:13116]
Reference
2  [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 314:45-8 (2001)
DOI:10.1016/S0304-3940(01)02277-7
  Sequence
[hsa:10858]
Reference
3  [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 42:14284-92 (2003)
DOI:10.1021/bi035512f
  Sequence
[hsa:10858]
Reference
4  [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 278:22980-8 (2003)
DOI:10.1074/jbc.M303415200
Reference
5  [PMID:12543708]
  Authors
Russell DW.
  Title
The enzymes, regulation, and genetics of bile acid synthesis.
  Journal
Annu Rev Biochem 72:137-74 (2003)
DOI:10.1146/annurev.biochem.72.121801.161712
Other DBs
ExplorEnz - The Enzyme Database: 1.14.14.25
IUBMB Enzyme Nomenclature: 1.14.14.25
ExPASy - ENZYME nomenclature database: 1.14.14.25
BRENDA, the Enzyme Database: 1.14.14.25
CAS: 50812-30-1 213327-78-7

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