KEGG   ENZYME: 1.14.14.25
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
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)
R07207
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
HSA10858(CYP46A1)
PTR453154(CYP46A1)
PPS100978372(CYP46A1)
GGO101142101
PON100440873
NLE100604931
MCC705843
MCF102140307(CYP46A1)
CSAB103229682(CYP46A1)
CATY105596681
PANU101024697
TGE112628803
RRO104654463
RBB108519071
TFN117071399
PTEH111538292
CJC100403833(CYP46A1)
SBQ101048333
CSYR103252598
MMUR105861542
OGA100967073
MMU13116(Cyp46a1)
MCAL110306885
MPAH110324576
RNO362782(Cyp46a1)
MCOC116081177
MUN110566352
CGE100769865
PLEU114701904
NGI103727655
HGL101708822
CPOC100729775
CCAN109694347
DORD105984431
DSP122118796
OCU100354574
OPI101521226
TUP102499401
CFA480432(CYP46A1)
VVP112930232
VLG121492487
AML100470338
UMR103673592
UAH113267281
UAR123778173
ELK111148659
LLV125105074
MPUF101688078
ORO101365372
EJU114207104
ZCA113909603
MLX118002291
FCA101093112
PYU121032271
PBG122469524
PTG102970492
PPAD109274544
AJU106972183
HHV120245736
BTA506438(CYP46A1)
BOM102270768
BBUB102397524
CHX102178217
OAS101117622
ODA120875206
CCAD122419692
SSC100512793
CFR102522998
CBAI105079921
CDK105095410
VPC102525462
BACU103014370
LVE103068707
OOR101280175
DLE111176091
PCAD102976598
PSIU116749111
ECB100051131
EPZ103550566
EAI106839686
MYB102251844
MYD102761609
MMYO118660179
MLF102442827
MNA107542730
PKL118704261
HAI109381070
DRO112311755
SHON118976840
AJM119037986
PDIC114492701
PHAS123808339
MMF118635840
RFQ117023672
PALE102898643
PGIG120619686
PVP105302289
RAY107518577
MJV108394816
TOD119238338
SARA101559384
LAV100677635
TMU101353740
DNM101426001
SHR100926883
PCW110222404
OAA100082015
GGA423450(CYP46A1)
PCOC116228856
MGP100546708
CJO107315364
NMEL110401402
APLA101792317
ACYG106036083
AFUL116489988
TGU100221970
LSR110481165
SCAN103826433
PMOA120503858
OTC121334142
PRUF121358280
GFR102044337
FAB101816121
PHI102099615
PMAJ107206481
CCAE111929830
CCW104686436
ETL114061692
ZAB102075066
FPG101918324
FCH102060075
CLV102086481
EGZ104124527
NNI104014834
ACUN113480441
TALA104363360
PADL103920698
ACHC115352583
AAM106482958
AROW112972680
NPD112956935
DNE112989932
ASN102376314
AMJ102574122(CYP46A1)
CPOO109321748
GGN109298462
PSS102449598
CMY102937516
CPIC101950833
TST117876150
CABI116821838
MRV120402810
ACS100552409 100552607
PVT110089659 110089661
SUND121919235 121919747
PBI103060230
PMUR107291347
TSR106554955
PGUT117665976
VKO123018897 123032045
PMUA114585569 114585577 114588390
ZVI118080655 118080672
GJA107121530 107121531
XLA100126648(cyp46a1.3.L) 108704878(cyp46a1.1.L) 379470(cyp46a1.2.L)
XTR100145328 100498621 613109(cyp46a1.3) 613111(cyp46a1.1) 780005(cyp46a1.2)
NPR108790745 108795063 108795064 108795072
RTEM120920042 120920174 120920768 120920898
BBUF120982153 120982331 120982402 120982403 120982405 120982407 120982408 120982409 120982490
BGAR122921922 122921989 122922124 122922206
DRE393433(cyp46a1.2) 393451(cyp46a1.4) 553543(cyp46a1.1) 641477(zgc:123299) 692332(cyp46a1.3)
SRX107728353 107747947
SANH107678664 107678670 107679679
SGH107555298 107572123
CCAR109113289 109113290
CAUA113121257 113121258
AMEX103039880
EEE113571915 113586723
TRU101061882 101077010
LCO104926956
NCC104967646
CGOB115003685
ELY117270337 117270909
PLEP121955336 121955367
SLUC116041942 116041943 116041944
ECRA117961088
PFLV114573150 114573151 114573152 114573153
GAT120808146
PPUG119195418
MSAM119908603 119908604
CUD121510023 121521266 121521471
MZE101466901 101484290 101484552 106676579 111500322
ONL100692681 100703511 100704054 102076821 102077122
OAU116315530 116315535 116315536 116332193 116332210 120433299
OLA101165021 101165274
OML112157723 112157725
XMA102224087 106699939
XCO114158714 114158715
XHE116734217 116734218
PRET103457823 103457824
PFOR103147687 103147688
PLAI106956892 106956894
PMEI106916229 106916230
GAF122825489 122825709
CVG107097647 107097654
CTUL119784179 119784180 119784181
GMU124882165 124882166 124882576
NFU107378149 107378150
KMR108231774 108231837 108231838 112450290
ALIM106525137 106525457 106525458
NWH119418059 119418455 119418456 119418457 119418458
AOCE111578258
CSEM103380705
POV109632307
SSEN122783686
HHIP117758428
LCF108898059
SDU111240402
SLAL111672518
XGL120788907
HCQ109523501
BPEC110161286 110173902 110173912
MALB109962169 109962173 109962186 109962187
SASA106571109 106571110 106571111 106608238
OTW112235780 112249824 112249887 112249888
OMY110522567 110529322 110529323 110529324 110529326 118965490
OGO123990517 123995395
ONE115107524 115122868
SALP111954047 111972528
SNH120019174 120024159 120024160
ELS105020476 105020477 105020478 106024908 109614563
SFM114910933 114912327 114912328 114912329
PKI111850949
AANG118230143 118230144 118230145 118230146 118230147
LOC102686415
PSPA121324127
ARUT117420692 117422588
LCM102350084
CMK103191174
RTP109920427
BFO118426351
BBEL109461803
OTU111417443
MYI110442672
PMAX117323274 117323275 117323276 117323277 117323279 117323755 117324632 117327808
ATEN116288258 116291041 116301076 116301543 116301544 116302235
XEN124434130 124434667 124434668 124434669 124434670 124434671 124435711 124445703
 » show all
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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