KEGG   ENZYME: 1.14.14.32
Entry
EC 1.14.14.32               Enzyme                                 
Name
17alpha-hydroxyprogesterone deacetylase;
C-17/C-20 lyase;
17alpha-hydroxyprogesterone acetaldehyde-lyase;
CYP17;
CYP17A1 (gene name);
17alpha-hydroxyprogesterone 17,20-lyase
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
17alpha-hydroxyprogesterone,NADPH---hemoprotein reductase:oxygen oxidoreductase (17alpha-hydroxylating, acetate-releasing)
Reaction(IUBMB)
(1) 17alpha-hydroxyprogesterone + [reduced NADPH---hemoprotein reductase] + O2 = androstenedione + acetate + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R08518];
(2) 17alpha-hydroxypregnenolone + [reduced NADPH---hemoprotein reductase] + O2 = 3beta-hydroxyandrost-5-en-17-one + acetate + [oxidized NADPH---hemoprotein reductase] + H2O [RN:R08517]
Reaction(KEGG)
R08517 R08518
Substrate
17alpha-hydroxyprogesterone [CPD:C01176];
[reduced NADPH---hemoprotein reductase] [CPD:C03024];
O2 [CPD:C00007];
17alpha-hydroxypregnenolone [CPD:C05138]
Product
androstenedione [CPD:C00280];
acetate [CPD:C00033];
[oxidized NADPH---hemoprotein reductase] [CPD:C03161];
H2O [CPD:C00001];
3beta-hydroxyandrost-5-en-17-one [CPD:C01227]
Comment
A microsomal cytochrome P-450 (heme-thiolate) protein that catalyses two independent reactions at the same active site - the 17-hydroxylation of pregnenolone and progesterone, which is part of glucocorticoid hormones biosynthesis (EC 1.14.14.19), and the conversion of the 17-hydroxylated products via a 17,20-lyase reaction to form androstenedione and 3beta-hydroxyandrost-5-en-17-one, leading to sex hormone biosynthesis. The activity of this reaction is dependent on the allosteric interaction of the enzyme with cytochrome b5 without any transfer of electrons from the cytochrome [2,4]. The enzymes from different organisms differ in their substrate specificity. While the enzymes from pig, hamster, and rat accept both 17alpha-hydroxyprogesterone and 17alpha-hydroxypregnenolone, the enzymes from human, bovine, sheep, goat, and bison do not accept the former, and the enzyme from guinea pig does not accept the latter [1].
History
EC 1.14.14.32 created 1976 as EC 4.1.2.30, transferred 2016 to EC 1.14.14.32
Pathway
ec00140  Steroid hormone biosynthesis
ec01100  Metabolic pathways
Orthology
K00512  steroid 17alpha-monooxygenase / 17alpha-hydroxyprogesterone deacetylase
Genes
HSA1586(CYP17A1)
PTR450141(CYP17A1)
PPS100989182(CYP17A1)
GGO101152080
PON100439753
NLE100596228
MCC678693(CYP17A1)
MCF102133235(CYP17A1)
CSAB103216445(CYP17A1)
CATY105581896
PANU101026704
TGE112630974
RRO104656530
RBB108515083
TFN117067514
PTEH111538851
CJC100400572(CYP17A1)
SBQ101048584
CSYR103251416
MMUR105874387
OGA100959209
MMU13074(Cyp17a1)
MCAL110285327
MPAH110334801
RNO25146(Cyp17a1)
MCOC116101357
MUN110556807
CGE100758683
PLEU114696710
NGI103744072
HGL101726496
CPOC100729670
CCAN109691327
DORD105986673
DSP122115926
OCU100346394
OPI101532918
TUP102472543
CFA477807(CYP17A1)
VVP112917782
VLG121485837
AML100476785
UMR103681600
UAH113251880
UAR123795915
ELK111145221
LLV125084794
MPUF101671806
ORO101384623
EJU114205173
ZCA113923407
MLX118025661
FCA493967(CYP17A1)
PYU121037171
PBG122493194
PTG102966057
PPAD109272832
AJU106966901
HHV120239617
BTA112441470 112444495 281739(CYP17A1)
BOM102270241 102270532
BIU109553214 109579081
BBUB102412624 112581551
CHX102182376 102182663(CYP17)
OAS105601846(CYP17) 493968(CYP17A1)
ODA120873501
CCAD122445953 122446740
SSC403330(CYP17A1)
CFR102519078
CBAI105081696
CDK105095024
VPC102528385
BACU103007900
LVE103081477
OOR101283719
DLE111172355
PCAD102989171
PSIU116741612
ECB100034232(CYP17A1)
EPZ103558137
EAI106838161
MYB102259343
MYD102761363
MMYO118670308
MLF102417518
MNA107542528
PKL118718912
HAI109379659
DRO112300189
SHON118999460
AJM119059642
PDIC114497592
PHAS123828947
MMF118631983
RFQ117036161
PALE102884618
PGIG120609141
PVP105309652
RAY107515566
MJV108410298
TOD119234280 119234908 119253889
SARA101555669
LAV100660963
TMU101354636
DNM101441314
MDO100028896
GAS123234242
SHR100915970
PCW110194957
OAA100080906
GGA425056(CYP17A1)
PCOC116231659
MGP100540331
CJO107316091
NMEL110399428
APLA101792920
ACYG106031836
AFUL116491607
TGU100218933
LSR110473583
SCAN103813852
PMOA120502140
OTC121341799
PRUF121350302
GFR102038147
FAB101821194
PHI102104333
PMAJ107206790
CCAE111931270
CCW104695563
ETL114071768
ZAB102070509
FPG101910363
FCH102054501
CLV102093575
EGZ104125602
NNI104022305
ACUN113481735
TALA104366646
PADL103916301
ACHC115348606
AAM106494668
AROW112967993
NPD112957074
DNE112989287
ASN102372221
AMJ102567971(CYP17A1)
CPOO109323822
GGN109287570
PSS102457785
CMY102945773
CPIC101933089
TST117880996
CABI116817103
MRV120408966
ACS100553634 100553834
PVT110077624
SUND121925460
PBI103063631
PMUR107290855
TSR106541312
PGUT117678655
VKO123024050
PMUA114597528
GJA107117909
XLA100036774(cyp17a1.L)
XTR100145650(cyp17a1)
NPR108784547 108784564
RTEM120946990
BBUF121004269 121005522
BGAR122942304
DRE399692(cyp17a1) 796487(cyp17a2)
SRX107707716 107750198
SANH107673162 107695149
SGH107574436 107588661
CCAR109076732 109111078
CAUA113041336 113056832 113074379 113085111
IPU100313515(cyp17) 108275468
PHYP113530739 113542020
SMEO124396975 124398983
AMEX103036160 111194069
EEE113570353 113585465
TRU100125766(cyp17a2) 100125798(cyp17a1) 115249663
LCO104935158 104936651
NCC104957534
CGOB115019922
ELY117248465 117272651
PLEP121954365 121962489
SLUC116034661 116053620
ECRA117935140 117960349
PFLV114546162 114571983
GAT100192329(cyp17a2) 100192330(cyp17a1)
PPUG119214573 119222944
MSAM119912282 119917252
CUD121504405 121510915
MZE101475441 101477086
ONL100702216(cyp17a2) 100703469(cyp17)
OAU116332169 116335890
OLA100125816(cyp17) 101170547(cyp17a2)
OML112156384 112161529
XMA102221767 102238057
XCO114138338 114157614
XHE116712776 116732588 116732589
PRET103476526 103480951
PFOR103149115 103155787
PLAI106934850 106958972
PMEI106916522 106928572
GAF122820816 122842871
CVG107083007 107099069
CTUL119773762 119787729
GMU124858740 124881307
NFU107375507 107396730
KMR108239115 108251556
ALIM106511002 106515325
NWH119417878 119430866
AOCE111563640 111579695
CSEM103387725 103389439
POV109634757 109639880
SSEN122766283 122781515
HHIP117751868 117775903
LCF108892361 108895342
SDU111233121 111239202
SLAL111661066 111669513
XGL120796819 120797261
HCQ109516617 109523214
BPEC110156961 110160276
MALB109972947 109973668
SASA106576693 106592366
OTW112238453 112252939
OMY100137017(cyp17a1) 110509408
OGO124013898 124040788
ONE115136350
SALP111951662 112078788
SNH120017914
ELS105006241 105008018
SFM108926160 108933747
PKI111836781 111859263
AANG118218511 118231945
LOC102683310 102696373
PSPA121321480 121326245
ARUT117409034 117415544
LCM102350866 102365866
CMK103177103
RTP109937010
BFO118425323 118425478
BBEL109475258 109487130
DSV119442568
RSAN119377837 119385974 119388354
RMP119159398
BGT106073674
HRF124129732
HRJ124264060 124275507
CRG105337314 117681976
PMAX117327584
MMER123555172 123555557 123558347
OSN115223139
ATEN116286226 116287483 116289234 116292213 116292286 116300224 116300467 116304432 116305619 116307262 116308086 116309069
XEN124452194 124452197 124452291 124455834
 » show all
Reference
1  [PMID:12693981]
  Authors
Gilep AA, Estabrook RW, Usanov SA
  Title
Molecular cloning and heterologous expression in E. coli of cytochrome P45017alpha. Comparison of structural and functional properties of substrate-specific cytochromes P450 from different species.
  Journal
Biochemistry (Mosc) 68:86-98 (2003)
DOI:10.1023/a:1022101703670
  Sequence
Reference
2  [PMID:9452426]
  Authors
Auchus RJ, Lee TC, Miller WL
  Title
Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer.
  Journal
J Biol Chem 273:3158-65 (1998)
DOI:10.1074/jbc.273.6.3158
Reference
3  [PMID:26668369]
  Authors
Mak PJ, Gregory MC, Denisov IG, Sligar SG, Kincaid JR
  Title
Unveiling the crucial intermediates in androgen production.
  Journal
Proc Natl Acad Sci U S A 112:15856-61 (2015)
DOI:10.1073/pnas.1519376113
  Sequence
[hsa:1586]
Reference
4  [PMID:26587646]
  Authors
Simonov AN, Holien JK, Yeung JC, Nguyen AD, Corbin CJ, Zheng J, Kuznetsov VL, Auchus RJ, Conley AJ, Bond AM, Parker MW, Rodgers RJ, Martin LL
  Title
Mechanistic Scrutiny Identifies a Kinetic Role for Cytochrome b5 Regulation of Human Cytochrome P450c17 (CYP17A1, P450 17A1).
  Journal
PLoS One 10:e0141252 (2015)
DOI:10.1371/journal.pone.0141252
  Sequence
[hsa:1586]
Reference
5  [PMID:26976652]
  Authors
Bhatt MR, Khatri Y, Rodgers RJ, Martin LL.
  Title
Role of cytochrome b5 in the modulation of the enzymatic activities of cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450 17A1).
  Journal
J Steroid Biochem Mol Biol 170:2-18 (2017)
DOI:10.1016/j.jsbmb.2016.02.033
Other DBs
ExplorEnz - The Enzyme Database: 1.14.14.32
IUBMB Enzyme Nomenclature: 1.14.14.32
ExPASy - ENZYME nomenclature database: 1.14.14.32
BRENDA, the Enzyme Database: 1.14.14.32
CAS: 62213-24-5

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