Entry
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
BRITE hierarchy
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)
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
Orthology
K00512 steroid 17alpha-monooxygenase / 17alpha-hydroxyprogesterone deacetylase
Genes
BTA : 112444495 281739(CYP17A1)
BBUB : 102412624 112581551
CHX : 102182376 102182663(CYP17A1A)
OAS : 105601846(CYP17) 493968(CYP17A1)
BTAX : 128067746 128071173
CCAD : 122445953 122446740
MBEZ : 129555394 129555959
TOD : 119234280 119234908 119253889
XLA : 100036774(cyp17a1.L)
BBUF : 121004269 121005522
DRE : 399692(cyp17a1) 796487(cyp17a2)
SANH : 107673162 107695149
CCAR : 109076732 109111078
CAUA : 113041336 113056832 113074379 113085111
CGIB : 127970183 128012018
PTET : 122334561 122356746
LROH : 127161931 127174815
PPRM : 120479844 120484073 120484098
MAMB : 125260617 125276970 125276972
CIDE : 127504550 127525002
MASI : 127413875 127418618
TROS : 130545059 130559140
MANU : 129416856 129431020
IPU : 100313515(cyp17) 108275468
PHYP : 113530739 113542020
SMEO : 124396975 124398983
AMEX : 103036160 111194069
CMAO : 118810050 118822544
CHAR : 105891434 105911586
TRU : 100125766(cyp17a2) 100125798(cyp17a1) 115249663
TBEN : 117480807 117483604
GACU : 117532575 117561641
PLEP : 121954365 121962489
SLUC : 116034661 116053620
ECRA : 117935140 117960349
PFLV : 114546162 114571983
GAT : 100192329(cyp17a2) 100192330(cyp17a1)
PPUG : 119214573 119222944
CLUM : 117743904 117747918
MSAM : 119912282 119917252
SCHU : 122870149 122883929
ALAT : 119026703 119033497
ONL : 100702216(cyp17a2) 100703469(cyp17)
OLA : 100125816(cyp17) 101170547(cyp17a2)
XHE : 116712776 116732588 116732589
PRET : 103476526 103480951
PFOR : 103149115 103155787
PLAI : 106934850 106958972
PMEI : 106916522 106928572
PPRL : 129355868 129360155 129376685
CTUL : 119773762 119787729
ALIM : 106511002 106515325
AOCE : 111563640 111579695
MCEP : 125009171 125018366
CSEM : 103387725 103389439
SSEN : 122766283 122781515
HHIP : 117751868 117775903
SLAL : 111661066 111669513
SSCV : 125978579 125992396
SBIA : 133494674 133509358
PTAO : 133472952 133485558
BPEC : 110156961 110160276
MALB : 109972947 109973668
BSPL : 114841926 114851252
SASA : 106576693 106592366
STRU : 115193858 115198019
OMY : 100137017(cyp17a1) 110509408
SALP : 111951662 112078788
CCLU : 121553719 121559195
AANG : 118218511 118231945
PSPA : 121321480 121326245
ARUT : 117409034 117415544
PMRN : 116939743 116941468
LRJ : 133345432 133345701 133346921
BBEL : 109475258 109487130
CVN : 111101403 111101451 111135334
CANU : 128160771 128161280 128167344 128185043
OED : 125646576 125646578 125646588 125663947 125675636
MMER : 123555172 123558347
ATEN : 116286226 116287483 116289234 116292213 116292286 116300224 116300467 116304432 116305619 116307262 116308086 116309069
XEN : 124452194 124452197 124452291 124455834
HSY : 130614135 130614136 130630581 130634454 130645371 130648549
» show all
Taxonomy
Reference
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
Sequence
Reference
Authors
Auchus RJ, Lee TC, Miller WL
Title
Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer.
Journal
Reference
Authors
Mak PJ, Gregory MC, Denisov IG, Sligar SG, Kincaid JR
Title
Unveiling the crucial intermediates in androgen production.
Journal
Sequence
Reference
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
Sequence
Reference
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
Other DBs