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
HSA: 1586(CYP17A1)
PTR: 450141(CYP17A1)
PPS: 100989182
GGO: 101152080
PON: 100439753
NLE: 100596228
MCC: 678693(CYP17A1)
MCF: 102133235(CYP17)
CSAB: 103216445(CYP17A1)
RRO: 104656530
RBB: 108515083
CJC: 100400572(CYP17A1)
SBQ: 101048584
MMU: 13074(Cyp17a1)
MCAL: 110285327
MPAH: 110334801
RNO: 25146(Cyp17a1)
MUN: 110556807
CGE: 100758683
NGI: 103744072
HGL: 101726496
CCAN: 109691327
OCU: 100346394
TUP: 102472543
CFA: 477807(CYP17A1)
VVP: 112917782
AML: 100476785
UMR: 103681600
UAH: 113251880
ORO: 101384623
ELK: 111145221
FCA: 493967(CYP17A1)
PTG: 102966057
PPAD: 109272832
AJU: 106966901
BTA: 112441470 112444495 281739(CYP17A1)
CHX: 102182376 102182663(CYP17)
OAS: 105601846(CYP17) 493968(CYP17A1)
SSC: 403330(CYP17A1)
CFR: 102519078
CDK: 105095024
BACU: 103007900
LVE: 103081477
OOR: 101283719
DLE: 111172355
PCAD: 102989171
ECB: 100034232(CYP17A1)
EPZ: 103558137
EAI: 106838161
MYB: 102259343
MYD: 102761363
MNA: 107542528
HAI: 109379659
DRO: 112300189
PALE: 102884618
RAY: 107515566
MJV: 108410298
LAV: 100660963
TMU: 101354636
MDO: 100028896
SHR: 100915970
PCW: 110194957
OAA: 100080906
GGA: 425056(CYP17A1)
MGP: 100540331
CJO: 107316091
NMEL: 110399428
APLA: 101792920
ACYG: 106031836
TGU: 100218933
LSR: 110473583
SCAN: 103813852
GFR: 102038147
FAB: 101821194
PHI: 102104333
PMAJ: 107206790
CCAE: 111931270
CCW: 104695563
ETL: 114071768
FPG: 101910363
FCH: 102054501
CLV: 102093575
EGZ: 104125602
NNI: 104022305
ACUN: 113481735
PADL: 103916301
AAM: 106494668
ASN: 102372221
AMJ: 102567971(CYP17A1)
PSS: 102457785
CMY: 102945773
CPIC: 101933089
PVT: 110077624
PBI: 103063631
PMUR: 107290855
TSR: 106541312
PMUA: 114597528
GJA: 107117909
XLA: 100036774(cyp17a1.L)
XTR: 100145650(cyp17a1)
DRE: 399692(cyp17a1) 796487(cyp17a2)
IPU: 100313515(cyp17) 108275468
TRU: 100125766(cyp17a2) 100125798(cyp17a1) 115249663
NCC: 104957534
ONL: 100702216(cyp17a2) 100703469(cyp17)
OLA: 100125816(cyp17) 101170547(cyp17a2)
OTW: 112252939
RTP: 109937010
SPU: 581339
FCD: 110861649
 » 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 (2016)
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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