Adrenal and interrenal steroidogenesis

Adrenal and interrenal steroidogenic cells convert cholesterol to pregnenolone and route it into corticosteroid or androgen branches. StAR-dependent cholesterol delivery and mitochondrial CYP11A cleavage supply the common entry. HSD3B and microsomal CYP17/CYP21 activities determine intermediate routes; mitochondrial CYP11 activities produce cortisol, corticosterone or aldosterone according to enzyme specificity and tissue expression. Human, mouse and zebrafish implementations share reactions but differ in paralog use, expression and terminal products.

MODULE:adrenal_steroidogenesisCOMPLETECONCRETEMetabolic Pathwaymodules/adrenal_steroidogenesis.yaml
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
Defines the biochemical entry and canonical corticosteroid/androgen branches.
PMID:26038201
Adrenal steroidogenesis and congenital adrenal hyperplasia.
Explains tissue zonation and comparative glucocorticoid output.
PMID:25445914
Origin of the response to adrenal and sex steroids: Roles of promiscuity and co-evolution of enzymes and steroid receptors.
Provides comparative enzyme evolution context without asserting universal pathway presence.

Primary reaction evidence and comparative member reviews govern the family restrictions. Exact family labels were read from PANTHER; source-disputed placements are explicit and do not establish evolutionary relationships. No unverified PAINT ancestral node is asserted. All eleven native representatives and two comparative fish paralogs have completed individual reviews; unresolved claims remain explicit. Free-text lyase and terminal 18-oxidase activities require manual conformance review against the proposed molecular functions in gene reviews.

15Nodes
14Parts
0Variant Sets
0Variants
17Annotons
17Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:adrenal_steroidogenesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

22 gene-function check(s) reflected in core functions · 0 conflict(s) · 29 evidence or coverage gap(s) (51 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
star_step_activity STAR (human)
UniProtKB:P49675
Family Representative 		cholesterol transfer activity
GO:0120020 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11a1_step_activity CYP11A1 (human)
UniProtKB:P05108
Family Representative 		cholesterol monooxygenase (side-chain-cleaving) activity
GO:0008386 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11a1_step_activity cyp11a1.2 (DANRE)
UniProtKB:A0A8M9Q8E0
Family Representative 		cholesterol monooxygenase (side-chain-cleaving) activity
GO:0008386 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hsd3b_preg_activity HSD3B2 (human)
UniProtKB:P26439
Family Representative 		3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity
GO:0003854 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hsd3b_preg_isomerase HSD3B2 (human)
UniProtKB:P26439
Family Representative 		steroid Delta-isomerase activity
GO:0004769 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp17_preg_activity CYP17A1 (human)
UniProtKB:P05093
Family Representative 		steroid 17-alpha-monooxygenase activity
GO:0004508 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp17_preg_activity cyp17a2 (DANRE)
UniProtKB:A7U483
Family Representative 		steroid 17-alpha-monooxygenase activity
GO:0004508 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp17_prog_activity CYP17A1 (human)
UniProtKB:P05093
Family Representative 		steroid 17-alpha-monooxygenase activity
GO:0004508 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp17_prog_activity cyp17a2 (DANRE)
UniProtKB:A7U483
Family Representative 		steroid 17-alpha-monooxygenase activity
GO:0004508 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hsd3b_17oh_activity HSD3B2 (human)
UniProtKB:P26439
Family Representative 		3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity
GO:0003854 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hsd3b_17oh_isomerase HSD3B2 (human)
UniProtKB:P26439
Family Representative 		steroid Delta-isomerase activity
GO:0004769 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp17_lyase_activity CYP17A1 (human)
UniProtKB:P05093
Family Representative 		steroid 17,20-lyase activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
cyp17_lyase_activity:required_function CYP17A1 (human)
UniProtKB:P05093
Family Representative 		steroid 17,20-lyase activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
hsd3b_dhea_activity HSD3B2 (human)
UniProtKB:P26439
Family Representative 		3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity
GO:0003854 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hsd3b_dhea_isomerase HSD3B2 (human)
UniProtKB:P26439
Family Representative 		steroid Delta-isomerase activity
GO:0004769 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp21_prog_activity CYP21A2 (human)
UniProtKB:P08686
Family Representative 		progesterone 21-hydroxylase activity
GO:0106309 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp21_17oh_activity CYP21A2 (human)
UniProtKB:P08686
Family Representative 		17-hydroxyprogesterone 21-hydroxylase activity
GO:0103069 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11_cortisol_activity CYP11B1 (human)
UniProtKB:P15538
Family Representative 		steroid 11-beta-monooxygenase activity
GO:0004507 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11_cortisol_activity cyp11c1 (DANRE)
UniProtKB:A1XRK1
Family Representative 		steroid 11-beta-monooxygenase activity
GO:0004507 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11_doc_activity CYP11B1 (human)
UniProtKB:P15538
Family Representative 		steroid 11-beta-monooxygenase activity
GO:0004507 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11_doc_activity CYP11B2 (human)
UniProtKB:P19099
Family Representative 		steroid 11-beta-monooxygenase activity
GO:0004507 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11_doc_activity Cyp11b2 (MOUSE)
UniProtKB:P15539
Family Representative 		steroid 11-beta-monooxygenase activity
GO:0004507 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11_18hydroxylation_activity CYP11B2 (human)
UniProtKB:P19099
Family Representative 		corticosterone 18-monooxygenase activity
GO:0047783 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11_18hydroxylation_activity Cyp11b2 (MOUSE)
UniProtKB:P15539
Family Representative 		corticosterone 18-monooxygenase activity
GO:0047783 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cyp11_18oxidation_activity CYP11B2 (human)
UniProtKB:P19099
Family Representative 		18-hydroxycorticosterone oxidase activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
cyp11_18oxidation_activity Cyp11b2 (MOUSE)
UniProtKB:P15539
Family Representative 		18-hydroxycorticosterone oxidase activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
cyp11_18oxidation_activity:required_function CYP11B2 (human)
UniProtKB:P19099
Family Representative 		18-hydroxycorticosterone oxidase activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
cyp11_18oxidation_activity:required_function Cyp11b2 (MOUSE)
UniProtKB:P15539
Family Representative 		18-hydroxycorticosterone oxidase activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
star_step_activity StAR cholesterol-transfer proteins
PANTHER:PTHR46489:SF1
Family 		cholesterol transfer activity
GO:0120020 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR46489:SF1.
cyp11a1_step_activity CYP11A cholesterol side-chain-cleavage enzymes
PANTHER:PTHR24279:SF3
Family 		cholesterol monooxygenase (side-chain-cleaving) activity
GO:0008386 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24279:SF3.
hsd3b_preg_activity Adrenal HSD3B dehydrogenase/isomerase proteins
PANTHER:PTHR43245:SF51
Family 		3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity
GO:0003854 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43245:SF51.
hsd3b_preg_isomerase Adrenal HSD3B dehydrogenase/isomerase proteins
PANTHER:PTHR43245:SF51
Family 		steroid Delta-isomerase activity
GO:0004769 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43245:SF51.
cyp17_preg_activity Adrenal/interrenal CYP17 hydroxylases
PANTHER:PTHR24289:SF13
Family 		steroid 17-alpha-monooxygenase activity
GO:0004508 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24289:SF13.
cyp17_preg_activity Adrenal/interrenal CYP17 hydroxylases
PANTHER:PTHR24289:SF19
Family 		steroid 17-alpha-monooxygenase activity
GO:0004508 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24289:SF19.
cyp17_prog_activity Adrenal/interrenal CYP17 hydroxylases
PANTHER:PTHR24289:SF13
Family 		steroid 17-alpha-monooxygenase activity
GO:0004508 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24289:SF13.
cyp17_prog_activity Adrenal/interrenal CYP17 hydroxylases
PANTHER:PTHR24289:SF19
Family 		steroid 17-alpha-monooxygenase activity
GO:0004508 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24289:SF19.
hsd3b_17oh_activity Adrenal HSD3B dehydrogenase/isomerase proteins
PANTHER:PTHR43245:SF51
Family 		3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity
GO:0003854 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43245:SF51.
hsd3b_17oh_isomerase Adrenal HSD3B dehydrogenase/isomerase proteins
PANTHER:PTHR43245:SF51
Family 		steroid Delta-isomerase activity
GO:0004769 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43245:SF51.
cyp17_lyase_activity Adrenal CYP17 enzymes with demonstrated 17,20-lyase activity
PANTHER:PTHR24289:SF13
Family 		steroid 17,20-lyase activity
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
cyp17_lyase_activity:required_function Adrenal CYP17 enzymes with demonstrated 17,20-lyase activity
PANTHER:PTHR24289:SF13
Family 		steroid 17,20-lyase activity
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
hsd3b_dhea_activity Adrenal HSD3B dehydrogenase/isomerase proteins
PANTHER:PTHR43245:SF51
Family 		3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity
GO:0003854 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43245:SF51.
hsd3b_dhea_isomerase Adrenal HSD3B dehydrogenase/isomerase proteins
PANTHER:PTHR43245:SF51
Family 		steroid Delta-isomerase activity
GO:0004769 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR43245:SF51.
cyp21_prog_activity Steroid CYP21 21-hydroxylases
PANTHER:PTHR24289:SF17
Family 		progesterone 21-hydroxylase activity
GO:0106309 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24289:SF17.
cyp21_17oh_activity Steroid CYP21 21-hydroxylases
PANTHER:PTHR24289:SF17
Family 		17-hydroxyprogesterone 21-hydroxylase activity
GO:0103069 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24289:SF17.
cyp11_cortisol_activity Corticosteroid 11beta-hydroxylases with cortisol output
PANTHER:PTHR24279:SF115
Family 		steroid 11-beta-monooxygenase activity
GO:0004507 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24279:SF115.
cyp11_cortisol_activity Corticosteroid 11beta-hydroxylases with cortisol output
PANTHER:PTHR24279:SF1
Family 		steroid 11-beta-monooxygenase activity
GO:0004507 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24279:SF1.
cyp11_doc_activity CYP11 enzymes converting deoxycorticosterone to corticosterone
PANTHER:PTHR24279:SF115
Family 		steroid 11-beta-monooxygenase activity
GO:0004507 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24279:SF115.
cyp11_doc_activity CYP11 enzymes converting deoxycorticosterone to corticosterone
PANTHER:PTHR24279:SF1
Family 		steroid 11-beta-monooxygenase activity
GO:0004507 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24279:SF1.
cyp11_18hydroxylation_activity CYP11 enzymes with demonstrated aldosterone-synthesis chemistry
PANTHER:PTHR24279:SF1
Family 		corticosterone 18-monooxygenase activity
GO:0047783 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR24279:SF1.
cyp11_18oxidation_activity CYP11 enzymes with demonstrated aldosterone-synthesis chemistry
PANTHER:PTHR24279:SF1
Family 		18-hydroxycorticosterone oxidase activity
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.
cyp11_18oxidation_activity:required_function CYP11 enzymes with demonstrated aldosterone-synthesis chemistry
PANTHER:PTHR24279:SF1
Family 		18-hydroxycorticosterone oxidase activity
No function ID 		No Function Id
The family function has no GO identifier for comparison; prose is not matched.

Gene-review completeness (11/11 grounded genes reviewed)

6 complete review(s) · 0 with deep research · 0 missing review · 11 reviewed but lacking deep research

Gene Review Complete Deep research
CYP11A1 P05108 ✓ ✓ ✗
cyp11a1.2 A0A8M9Q8E0 ✓ ✓ ✗
CYP11B1 P15538 ✓ 40/46 ✗
Cyp11b2 P15539 ✓ 45/46 ✗
CYP11B2 P19099 ✓ 54/55 ✗
cyp11c1 A1XRK1 ✓ 8/9 ✗
CYP17A1 P05093 ✓ ✓ ✗
cyp17a2 A7U483 ✓ ✓ ✗
CYP21A2 P08686 ✓ ✓ ✗
HSD3B2 P26439 ✓ ✓ ✗
STAR P49675 ✓ 43/44 ✗

Details

Context
VertebrataNCBITaxon:7742

Vertebrata is a non-universal envelope for a repertoire of adrenal/interrenal reactions, not a claim that each vertebrate produces every endpoint. Native exemplars are human, mouse and zebrafish. Individual branches require the appropriate enzyme specificity and tissue expression.

Adrenal/interrenal steroidogenic reaction networkMetabolic Pathwayadrenal_steroidogenesis
Context
VertebrataNCBITaxon:7742

Vertebrata is a non-universal envelope for a repertoire of adrenal/interrenal reactions, not a claim that each vertebrate produces every endpoint. Native exemplars are human, mouse and zebrafish. Individual branches require the appropriate enzyme specificity and tissue expression.

The two entry steps are shared; optional downstream parts encode alternative branches in a species/tissue-specific realization, not dispensability of a reaction within a chosen branch. Display order is not a single linear chronology. HSD3B reactions are split by substrate and by dehydrogenase/isomerase activity so the graph does not imply an artificial CYP17-HSD3B cycle. CYP17A2 has hydroxylase activity without lyase; CYP11C1 is not an aldosterone synthase merely because it shares a named PANTHER subfamily. Redox partners (POR, ferredoxin reductase and ferredoxin, with cytochrome b5 modulation) are required biochemical context outside the present member boundary. Cortisol/cortisone interconversion, steroid sulfation, aromatization, backdoor and downstream 11-oxygenated androgen pathways are outside scope. The normal adult mouse/rat corticosterone pattern has a documented fetal mouse CYP17 exception. The two additional reviewed zebrafish paralogs cyp11a1.1 and cyp17a1 are comparative evidence, not asserted interrenal representatives.

Connections

star_step -> cyp11a1_step Provides Input For
cholesterol connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through cholesterol.
cyp11a1_step -> hsd3b_preg Provides Input For
pregnenolone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through pregnenolone.
cyp11a1_step -> cyp17_preg Provides Input For
pregnenolone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through pregnenolone.
hsd3b_preg -> cyp17_prog Provides Input For
progesterone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through progesterone.
hsd3b_preg -> cyp21_prog Provides Input For
progesterone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through progesterone.
cyp17_preg -> hsd3b_17oh Provides Input For
17alpha-hydroxypregnenolone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through 17alpha-hydroxypregnenolone.
cyp17_preg -> cyp17_lyase Provides Input For
17alpha-hydroxypregnenolone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through 17alpha-hydroxypregnenolone.
cyp17_prog -> cyp21_17oh Provides Input For
17alpha-hydroxyprogesterone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through 17alpha-hydroxyprogesterone.
hsd3b_17oh -> cyp21_17oh Provides Input For
17alpha-hydroxyprogesterone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through 17alpha-hydroxyprogesterone.
cyp17_lyase -> hsd3b_dhea Provides Input For
dehydroepiandrosterone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through dehydroepiandrosterone.
cyp21_prog -> cyp11_doc Provides Input For
11-deoxycorticosterone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through 11-deoxycorticosterone.
cyp21_17oh -> cyp11_cortisol Provides Input For
11-deoxycortisol connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The source describes the precursor-product relation through 11-deoxycortisol.
cyp11_doc -> cyp11_18hydroxylation Provides Input For
corticosterone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:2256920
Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.
The source describes the precursor-product relation through corticosterone.
18-hydroxycorticosterone connects these reactions in realizations expressing the required enzymes in compatible tissue and cellular contexts.
PMID:2256920
Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.
The source describes the precursor-product relation through 18-hydroxycorticosterone.
Part 1: Cholesterol delivery to the inner mitochondrial membrane
Cholesterol delivery to the inner mitochondrial membraneReactionstar_step
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The review distinguishes acute StAR-dependent cholesterol delivery from CYP11A1 catalysis.
PMID:12372832
Transfer of cholesterol between phospholipid vesicles mediated by the steroidogenic acute regulatory protein (StAR).
Purified StAR transfers cholesterol between artificial membranes, supporting a direct transfer activity rather than only a requirement inferred from steroid output.
PMID:7761400
Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13.
Coexpression of human StAR with P450scc and adrenodoxin increases pregnenolone synthesis, linking transfer to the downstream steroidogenic reaction.
PMID:12530629
The steroidogenic acute regulatory protein, StAR, works only at the outer mitochondrial membrane.
Membrane-targeted StAR constructs identify the outer mitochondrial membrane as the site of productive activity.

Annotons

Cholesterol delivery to the inner mitochondrial membrane
star_step_activity
Participant: Family: StAR cholesterol-transfer proteins
Family:
StAR cholesterol-transfer proteins The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: STAR (human)UniProtKB:P49675
Required Function:
cholesterol transfer activityGO:0120020

Function

cholesterol transfer activityGO:0120020
Substrates: cholesterol at the outer mitochondrial membrane
Products: cholesterol accessible to CYP11A

Locations

mitochondrial outer membraneGO:0005741

StAR promotes acute mitochondrial cholesterol availability for CYP11A catalysis; it does not cleave cholesterol.

Part 2: Cholesterol to pregnenolone
Cholesterol to pregnenoloneReactioncyp11a1_step
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
The review describes mitochondrial cholesterol cleavage to pregnenolone and the requirement for ferredoxin/redox partners.
PMID:31693487
The P450 side-chain cleavage enzyme Cyp11a2 facilitates steroidogenesis in zebrafish.
Stable zebrafish cyp11a2 mutants have glucocorticoid and androgen deficiencies, supporting interrenal and gonadal steroidogenesis by the gene now named cyp11a1.2.
PMID:21636783
Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.
Human CYP11A1/ferredoxin structures and substrate/intermediate complexes support sequential cholesterol hydroxylations and side-chain cleavage, with redox partners required for catalysis.

NADPH-derived electrons are supplied through ferredoxin reductase and ferredoxin; these partners are required context outside this module membership boundary.

Annotons

Cholesterol to pregnenolone
cyp11a1_step_activity
Participant: Family: CYP11A cholesterol side-chain-cleavage enzymes
Family:
CYP11A cholesterol side-chain-cleavage enzymes The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: CYP11A1 (human)UniProtKB:P05108 cyp11a1.2 (DANRE)UniProtKB:A0A8M9Q8E0
Required Function:
cholesterol monooxygenase (side-chain-cleaving) activityGO:0008386

Function

cholesterol monooxygenase (side-chain-cleaving) activityGO:0008386
Substrates: cholesterol molecular oxygen reduced ferredoxin
Products: pregnenolone 4-methylpentanal

Locations

mitochondrial inner membraneGO:0005743

CYP11A performs sequential oxidations and side-chain cleavage. The zebrafish representative is the paralog now named cyp11a1.2, supported in native interrenal steroidogenesis.

Part 3: pregnenolone to progesterone (optional)
pregnenolone to progesteroneReactionhsd3b_preg
PMID:1944309
Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads.
Expression of human HSD3B isoenzymes establishes NAD+-dependent pregnenolone and DHEA conversion and predominant type II expression in adrenal and gonadal tissue.
PMID:21930695
Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis.
Human HSD3B2 supplies dehydrogenase and isomerase reactions and can associate peripherally with the inner mitochondrial membrane facing the intermembrane space; its location is not restricted to the ER.

Annotons

pregnenolone to progesterone
hsd3b_preg_activity
Participant: Family: Adrenal HSD3B dehydrogenase/isomerase proteins
Family:
Adrenal HSD3B dehydrogenase/isomerase proteins The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded. Source disagreement: UniProt places HSD3B2 in PTHR43245:SF51, while the pinned PANTHER classification places it in PTHR10366:SF784. The selected ID records the UniProt assignment, not a resolved evolutionary judgment; no ancestral transfer is inferred.
Representative Members: HSD3B2 (human)UniProtKB:P26439
Required Function:
3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activityGO:0003854

Function

3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activityGO:0003854
Substrates: pregnenolone NAD+
Products: pregn-5-ene-3,20-dione NADH

Locations

endoplasmic reticulum membraneGO:0005789 mitochondrial inner membraneGO:0005743

HSD3B couples NAD+-dependent oxidation of pregnenolone to pregn-5-ene-3,20-dione with Delta5-to-Delta4 isomerization yielding progesterone.

pregnenolone to progesterone
hsd3b_preg_isomerase
Participant: Family: Adrenal HSD3B dehydrogenase/isomerase proteins
Family:
Adrenal HSD3B dehydrogenase/isomerase proteins The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded. Source disagreement: UniProt places HSD3B2 in PTHR43245:SF51, while the pinned PANTHER classification places it in PTHR10366:SF784. The selected ID records the UniProt assignment, not a resolved evolutionary judgment; no ancestral transfer is inferred.
Representative Members: HSD3B2 (human)UniProtKB:P26439
Required Function:
steroid Delta-isomerase activityGO:0004769

Function

steroid Delta-isomerase activityGO:0004769
Substrates: pregn-5-ene-3,20-dione
Products: progesterone

Locations

endoplasmic reticulum membraneGO:0005789 mitochondrial inner membraneGO:0005743

HSD3B couples NAD+-dependent oxidation of pregnenolone to pregn-5-ene-3,20-dione with Delta5-to-Delta4 isomerization yielding progesterone.

Connections

pregn-5-ene-3,20-dione is the intermediate connecting dehydrogenation and isomerization.
PMID:1944309
Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads.
Expression of human HSD3B isoenzymes establishes NAD+-dependent pregnenolone and DHEA conversion and predominant type II expression in adrenal and gonadal tissue.
PMID:21930695
Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis.
Human HSD3B2 supplies dehydrogenase and isomerase reactions and can associate peripherally with the inner mitochondrial membrane facing the intermembrane space; its location is not restricted to the ER.
Part 4: Pregnenolone 17alpha-hydroxylation (optional)
Pregnenolone 17alpha-hydroxylationReactioncyp17_preg
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
Human CYP17A1 hydroxylates pregnenolone at C17 as one route into corticosteroid or androgen synthesis.
PMID:25533464
Structural and kinetic basis of steroid 17α,20-lyase activity in teleost fish cytochrome P450 17A1 and its absence in cytochrome P450 17A2.
Purified zebrafish CYP17A1 performs hydroxylase and lyase reactions, whereas CYP17A2 performs hydroxylation without lyase activity even with cytochrome b5.
PMID:35733778
Characterization of the Interrenal Gland and Sexual Traits Development in cyp17a2-Deficient Zebrafish.
Loss of zebrafish cyp17a2 reduces adult cortisol and alters interrenal/HPI function, establishing native corticosteroid-pathway participation beyond the purified-enzyme comparison.

Annotons

Pregnenolone 17alpha-hydroxylation
cyp17_preg_activity
Participant: Family: Adrenal/interrenal CYP17 hydroxylases
Family:
Adrenal/interrenal CYP17 hydroxylases The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: CYP17A1 (human)UniProtKB:P05093 cyp17a2 (DANRE)UniProtKB:A7U483
Required Function:
steroid 17-alpha-monooxygenase activityGO:0004508

Function

steroid 17-alpha-monooxygenase activityGO:0004508
Substrates: pregnenolone molecular oxygen reducing equivalents from POR
Products: 17alpha-hydroxypregnenolone

Locations

endoplasmic reticulum membraneGO:0005789

CYP17A1 or the hydroxylase-only fish Cyp17a2 hydroxylates pregnenolone at C17. Hydroxylation does not imply subsequent lyase competence. ER-membrane localization is comparative mammalian pathway context; the zebrafish Cyp17a2 gene review supports membrane localization only, with no direct ER-localization assay.

Part 5: Progesterone 17alpha-hydroxylation (optional)
Progesterone 17alpha-hydroxylationReactioncyp17_prog
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
Human CYP17A1 hydroxylates progesterone at C17 as an alternative route to 17alpha-hydroxyprogesterone.
PMID:25533464
Structural and kinetic basis of steroid 17α,20-lyase activity in teleost fish cytochrome P450 17A1 and its absence in cytochrome P450 17A2.
Purified zebrafish CYP17A1 performs hydroxylase and lyase reactions, whereas CYP17A2 performs hydroxylation without lyase activity even with cytochrome b5.

Annotons

Progesterone 17alpha-hydroxylation
cyp17_prog_activity
Participant: Family: Adrenal/interrenal CYP17 hydroxylases
Family:
Adrenal/interrenal CYP17 hydroxylases The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: CYP17A1 (human)UniProtKB:P05093 cyp17a2 (DANRE)UniProtKB:A7U483
Required Function:
steroid 17-alpha-monooxygenase activityGO:0004508

Function

steroid 17-alpha-monooxygenase activityGO:0004508
Substrates: progesterone molecular oxygen reducing equivalents from POR
Products: 17alpha-hydroxyprogesterone

Locations

endoplasmic reticulum membraneGO:0005789

CYP17 hydroxylation of progesterone supplies the 17-hydroxylated corticosteroid branch. Adult mouse/rat adrenal expression differs from fetal mouse and human expression. ER-membrane localization is comparative mammalian pathway context; the zebrafish Cyp17a2 gene review supports membrane localization only, with no direct ER-localization assay.

Part 6: 17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone (optional)
17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesteroneReactionhsd3b_17oh
PMID:21930695
Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis.
Human HSD3B2 supplies dehydrogenase and isomerase reactions and can associate peripherally with the inner mitochondrial membrane facing the intermembrane space; its location is not restricted to the ER.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
HSD3B dehydrogenation and isomerization convert 17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone.

Annotons

17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone
hsd3b_17oh_activity
Participant: Family: Adrenal HSD3B dehydrogenase/isomerase proteins
Family:
Adrenal HSD3B dehydrogenase/isomerase proteins The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded. Source disagreement: UniProt places HSD3B2 in PTHR43245:SF51, while the pinned PANTHER classification places it in PTHR10366:SF784. The selected ID records the UniProt assignment, not a resolved evolutionary judgment; no ancestral transfer is inferred.
Representative Members: HSD3B2 (human)UniProtKB:P26439
Required Function:
3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activityGO:0003854

Function

3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activityGO:0003854
Substrates: 17alpha-hydroxypregnenolone NAD+
Products: 17alpha-hydroxypregn-5-ene-3,20-dione NADH

Locations

endoplasmic reticulum membraneGO:0005789 mitochondrial inner membraneGO:0005743

HSD3B couples NAD+-dependent oxidation of 17alpha-hydroxypregnenolone to 17alpha-hydroxypregn-5-ene-3,20-dione with Delta5-to-Delta4 isomerization yielding 17alpha-hydroxyprogesterone.

17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone
hsd3b_17oh_isomerase
Participant: Family: Adrenal HSD3B dehydrogenase/isomerase proteins
Family:
Adrenal HSD3B dehydrogenase/isomerase proteins The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded. Source disagreement: UniProt places HSD3B2 in PTHR43245:SF51, while the pinned PANTHER classification places it in PTHR10366:SF784. The selected ID records the UniProt assignment, not a resolved evolutionary judgment; no ancestral transfer is inferred.
Representative Members: HSD3B2 (human)UniProtKB:P26439
Required Function:
steroid Delta-isomerase activityGO:0004769

Function

steroid Delta-isomerase activityGO:0004769
Substrates: 17alpha-hydroxypregn-5-ene-3,20-dione
Products: 17alpha-hydroxyprogesterone

Locations

endoplasmic reticulum membraneGO:0005789 mitochondrial inner membraneGO:0005743

HSD3B couples NAD+-dependent oxidation of 17alpha-hydroxypregnenolone to 17alpha-hydroxypregn-5-ene-3,20-dione with Delta5-to-Delta4 isomerization yielding 17alpha-hydroxyprogesterone.

Connections

17alpha-hydroxypregn-5-ene-3,20-dione is the intermediate connecting dehydrogenation and isomerization.
PMID:21930695
Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis.
Human HSD3B2 supplies dehydrogenase and isomerase reactions and can associate peripherally with the inner mitochondrial membrane facing the intermembrane space; its location is not restricted to the ER.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
HSD3B dehydrogenation and isomerization convert 17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone.
Part 7: 17alpha-Hydroxypregnenolone to DHEA (optional)
17alpha-Hydroxypregnenolone to DHEAReactioncyp17_lyase
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
Human CYP17A1 cleaves 17alpha-hydroxypregnenolone to DHEA; the lyase reaction is distinct from the preceding hydroxylation.
PMID:40340376
Similar Rates of Second Electron Transfer and Single-Turnover Dehydroepiandrosterone Formation for Oxyferrous Human Cytochrome P450 17A1 (Steroid 17-Hydroxylase/17,20-lyase)-17-hydroxypregnenolone Complex with Either Human Cytochrome P450-Oxidoreductase or Human Cytochrome b(5).
Reduced human cytochrome b5 can supply the second electron for CYP17A1 lyase turnover in a defined reconstituted assay; an exclusively non-redox mechanism is too strong.

Cytochrome b5 stimulates lyase activity and can provide the second electron in reconstituted assays; it is not described as exclusively allosteric. No specific GO lyase identifier is asserted. The weak human delta4 lyase route is not the principal androgen branch shown here.

Annotons

17alpha-Hydroxypregnenolone to DHEA
cyp17_lyase_activity
Participant: Family: Adrenal CYP17 enzymes with demonstrated 17,20-lyase activity
Family:
Adrenal CYP17 enzymes with demonstrated 17,20-lyase activity The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: CYP17A1 (human)UniProtKB:P05093
Required Function:
steroid 17,20-lyase activity

Function

steroid 17,20-lyase activity
Substrates: 17alpha-hydroxypregnenolone molecular oxygen reducing equivalents
Products: dehydroepiandrosterone acetate

Locations

endoplasmic reticulum membraneGO:0005789

Human CYP17A1 oxidative C17-C20 cleavage produces DHEA. This activity is distinct from GO:0004508 hydroxylation and is not supplied by fish Cyp17a2.

Part 8: dehydroepiandrosterone to androstenedione (optional)
dehydroepiandrosterone to androstenedioneReactionhsd3b_dhea
PMID:1944309
Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads.
Expression of human HSD3B isoenzymes establishes NAD+-dependent pregnenolone and DHEA conversion and predominant type II expression in adrenal and gonadal tissue.
PMID:21930695
Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis.
Human HSD3B2 supplies dehydrogenase and isomerase reactions and can associate peripherally with the inner mitochondrial membrane facing the intermembrane space; its location is not restricted to the ER.

Annotons

dehydroepiandrosterone to androstenedione
hsd3b_dhea_activity
Participant: Family: Adrenal HSD3B dehydrogenase/isomerase proteins
Family:
Adrenal HSD3B dehydrogenase/isomerase proteins The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded. Source disagreement: UniProt places HSD3B2 in PTHR43245:SF51, while the pinned PANTHER classification places it in PTHR10366:SF784. The selected ID records the UniProt assignment, not a resolved evolutionary judgment; no ancestral transfer is inferred.
Representative Members: HSD3B2 (human)UniProtKB:P26439
Required Function:
3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activityGO:0003854

Function

3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activityGO:0003854
Substrates: dehydroepiandrosterone NAD+
Products: androst-5-ene-3,17-dione NADH

Locations

endoplasmic reticulum membraneGO:0005789 mitochondrial inner membraneGO:0005743

HSD3B couples NAD+-dependent oxidation of dehydroepiandrosterone to androst-5-ene-3,17-dione with Delta5-to-Delta4 isomerization yielding androstenedione.

dehydroepiandrosterone to androstenedione
hsd3b_dhea_isomerase
Participant: Family: Adrenal HSD3B dehydrogenase/isomerase proteins
Family:
Adrenal HSD3B dehydrogenase/isomerase proteins The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded. Source disagreement: UniProt places HSD3B2 in PTHR43245:SF51, while the pinned PANTHER classification places it in PTHR10366:SF784. The selected ID records the UniProt assignment, not a resolved evolutionary judgment; no ancestral transfer is inferred.
Representative Members: HSD3B2 (human)UniProtKB:P26439
Required Function:
steroid Delta-isomerase activityGO:0004769

Function

steroid Delta-isomerase activityGO:0004769
Substrates: androst-5-ene-3,17-dione
Products: androstenedione

Locations

endoplasmic reticulum membraneGO:0005789 mitochondrial inner membraneGO:0005743

HSD3B couples NAD+-dependent oxidation of dehydroepiandrosterone to androst-5-ene-3,17-dione with Delta5-to-Delta4 isomerization yielding androstenedione.

Connections

androst-5-ene-3,17-dione is the intermediate connecting dehydrogenation and isomerization.
PMID:1944309
Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads.
Expression of human HSD3B isoenzymes establishes NAD+-dependent pregnenolone and DHEA conversion and predominant type II expression in adrenal and gonadal tissue.
PMID:21930695
Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis.
Human HSD3B2 supplies dehydrogenase and isomerase reactions and can associate peripherally with the inner mitochondrial membrane facing the intermembrane space; its location is not restricted to the ER.
Part 9: Progesterone to deoxycorticosterone (optional)
Progesterone to deoxycorticosteroneReactioncyp21_prog
PMID:16984992
Four novel missense mutations in the CYP21A2 gene detected in Russian patients suffering from the classical form of congenital adrenal hyperplasia: identification, functional characterization, and structural analysis.
Functional CYP21A2 assays test both progesterone-to-deoxycorticosterone and 17-hydroxyprogesterone-to-11-deoxycortisol conversion.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
CYP21 21-hydroxylation of progesterone produces deoxycorticosterone.

Annotons

Progesterone to deoxycorticosterone
cyp21_prog_activity
Participant: Family: Steroid CYP21 21-hydroxylases
Family:
Steroid CYP21 21-hydroxylases The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded. Source disagreement: UniProt places CYP21A2 in PTHR24289:SF17, while the pinned PANTHER classification places it in PTHR24281:SF83. The selected ID records the UniProt assignment, not a resolved evolutionary judgment; no ancestral transfer is inferred.
Representative Members: CYP21A2 (human)UniProtKB:P08686
Required Function:
progesterone 21-hydroxylase activityGO:0106309

Function

progesterone 21-hydroxylase activityGO:0106309
Substrates: progesterone molecular oxygen reducing equivalents from POR
Products: 11-deoxycorticosterone

Locations

endoplasmic reticulum membraneGO:0005789

CYP21 21-hydroxylation supplies deoxycorticosterone for corticosterone or aldosterone synthesis, according to the terminal enzymes and tissue context.

Part 10: 17alpha-Hydroxyprogesterone to 11-deoxycortisol (optional)
17alpha-Hydroxyprogesterone to 11-deoxycortisolReactioncyp21_17oh
PMID:16984992
Four novel missense mutations in the CYP21A2 gene detected in Russian patients suffering from the classical form of congenital adrenal hyperplasia: identification, functional characterization, and structural analysis.
Functional CYP21A2 assays test both progesterone-to-deoxycorticosterone and 17-hydroxyprogesterone-to-11-deoxycortisol conversion.
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
CYP21 21-hydroxylation of 17alpha-hydroxyprogesterone produces 11-deoxycortisol.

Annotons

17alpha-Hydroxyprogesterone to 11-deoxycortisol
cyp21_17oh_activity
Participant: Family: Steroid CYP21 21-hydroxylases
Family:
Steroid CYP21 21-hydroxylases The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded. Source disagreement: UniProt places CYP21A2 in PTHR24289:SF17, while the pinned PANTHER classification places it in PTHR24281:SF83. The selected ID records the UniProt assignment, not a resolved evolutionary judgment; no ancestral transfer is inferred.
Representative Members: CYP21A2 (human)UniProtKB:P08686
Required Function:
17-hydroxyprogesterone 21-hydroxylase activityGO:0103069

Function

17-hydroxyprogesterone 21-hydroxylase activityGO:0103069
Substrates: 17alpha-hydroxyprogesterone molecular oxygen reducing equivalents from POR
Products: 11-deoxycortisol

Locations

endoplasmic reticulum membraneGO:0005789

CYP21 21-hydroxylation of 17alpha-hydroxyprogesterone supplies the immediate cortisol precursor.

Part 11: 11-Deoxycortisol to cortisol (optional)
11-Deoxycortisol to cortisolReactioncyp11_cortisol
PMID:21051590
The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.
Human CYP11B1 converts 11-deoxycortisol to cortisol through 11beta-hydroxylation.
PMID:1741400
Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans.
Human CYP11B2 and CYP11B1 are distinct gene products; recombinant CYP11B2 makes aldosterone while the assayed CYP11B1 does not complete that pathway.
PMID:32222764
Zebrafish cyp11c1 Knockout Reveals the Roles of 11-ketotestosterone and Cortisol in Sexual Development and Reproduction.
Zebrafish cyp11c1 loss disrupts cortisol and 11-oxygenated androgen production; terminal 11-ketotestosterone oxidation is a downstream reaction outside this enzyme and module.
PMID:32805708
11β-Hydroxylase loss disrupts steroidogenesis and reproductive function in zebrafish.
An independent zebrafish cyp11c1 mutant study corroborates cortisol deficiency. Its reproductive consequences are distinct from the directly modeled hydroxylation step.

The inner-mitochondrial-membrane location is established human CYP11 biochemistry and family-level context; the fish review leaves target-specific experimental membrane localization unresolved. GO:0004507 is broader than the stated substrate, so the explicit 11-deoxycortisol substrate restriction remains essential.

Annotons

11-Deoxycortisol to cortisol
cyp11_cortisol_activity
Participant: Family: Corticosteroid 11beta-hydroxylases with cortisol output
Family:
Corticosteroid 11beta-hydroxylases with cortisol output The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: CYP11B1 (human)UniProtKB:P15538 cyp11c1 (DANRE)UniProtKB:A1XRK1
Required Function:
steroid 11-beta-monooxygenase activityGO:0004507

Function

steroid 11-beta-monooxygenase activityGO:0004507
Substrates: 11-deoxycortisol molecular oxygen reduced ferredoxin
Products: cortisol

Locations

mitochondrial inner membraneGO:0005743

Cortisol-producing CYP11 enzymes perform terminal 11beta-hydroxylation. Fish Cyp11c1 is selected for this reaction, not for aldosterone production.

Part 12: Deoxycorticosterone to corticosterone (optional)
Deoxycorticosterone to corticosteroneReactioncyp11_doc
PMID:2256920
Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.
Recombinant human aldosterone synthase converts deoxycorticosterone through corticosterone and 18-hydroxycorticosterone to aldosterone, separating intermediate hydroxylations from terminal oxidation.
PMID:7588219
Developmentally regulated expression of adrenal 17 alpha-hydroxylase cytochrome P450 in the mouse embryo.
Mouse fetal adrenal Cyp17 expression and hydroxylase activity are transient; adult mouse and rat corticosterone predominance must not be generalized to all developmental stages.
PMID:1686470
Different isozymes of mouse 11 beta-hydroxylase produce mineralocorticoids and glucocorticoids.
Mouse Cyp11b2 expression in COS-7 cells supports aldosterone synthesis, in contrast to the Cyp11b1 comparator.
PMID:15731365
Homeostatic responses in the adrenal cortex to the absence of aldosterone in mice.
Disruption of mouse Cyp11b2 eliminates detectable circulating aldosterone, confirming the native adrenal requirement alongside direct enzyme evidence.

CYP11B1 and CYP11B2 can perform this chemical step. The edge onward to aldosterone describes continued CYP11B2 chemistry in the appropriate context, not obligatory transport from a CYP11B1-expressing zone.

Annotons

Deoxycorticosterone to corticosterone
cyp11_doc_activity
Participant: Family: CYP11 enzymes converting deoxycorticosterone to corticosterone
Family:
CYP11 enzymes converting deoxycorticosterone to corticosterone The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: CYP11B1 (human)UniProtKB:P15538 CYP11B2 (human)UniProtKB:P19099 Cyp11b2 (MOUSE)UniProtKB:P15539
Required Function:
steroid 11-beta-monooxygenase activityGO:0004507

Function

steroid 11-beta-monooxygenase activityGO:0004507
Substrates: 11-deoxycorticosterone molecular oxygen reduced ferredoxin
Products: corticosterone

Locations

mitochondrial inner membraneGO:0005743

11beta-Hydroxylation yields corticosterone, a glucocorticoid endpoint in adult mice/rats and an intermediate for aldosterone where the subsequent chemistry occurs.

Part 13: Corticosterone to 18-hydroxycorticosterone (optional)
Corticosterone to 18-hydroxycorticosteroneReactioncyp11_18hydroxylation
PMID:2256920
Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.
Recombinant human aldosterone synthase converts deoxycorticosterone through corticosterone and 18-hydroxycorticosterone to aldosterone, separating intermediate hydroxylations from terminal oxidation.
PMID:23322723
Structural insights into aldosterone synthase substrate specificity and targeted inhibition.
Human CYP11B2 structural and biochemical data explain substrate recognition, release of reaction intermediates and the additional terminal C18 oxidation relative to CYP11B1.
PMID:1686470
Different isozymes of mouse 11 beta-hydroxylase produce mineralocorticoids and glucocorticoids.
Mouse Cyp11b2 expression in COS-7 cells supports aldosterone synthesis, in contrast to the Cyp11b1 comparator.
PMID:15731365
Homeostatic responses in the adrenal cortex to the absence of aldosterone in mice.
Disruption of mouse Cyp11b2 eliminates detectable circulating aldosterone, confirming the native adrenal requirement alongside direct enzyme evidence.

Annotons

Corticosterone to 18-hydroxycorticosterone
cyp11_18hydroxylation_activity
Participant: Family: CYP11 enzymes with demonstrated aldosterone-synthesis chemistry
Family:
CYP11 enzymes with demonstrated aldosterone-synthesis chemistry The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: CYP11B2 (human)UniProtKB:P19099 Cyp11b2 (MOUSE)UniProtKB:P15539
Required Function:
corticosterone 18-monooxygenase activityGO:0047783

Function

corticosterone 18-monooxygenase activityGO:0047783
Substrates: corticosterone molecular oxygen reduced ferredoxin
Products: 18-hydroxycorticosterone

Locations

mitochondrial inner membraneGO:0005743

C18 hydroxylation supplies the immediate substrate for aldosterone-forming oxidation. This step alone is insufficient to establish aldosterone synthase competence.

Part 14: 18-Hydroxycorticosterone to aldosterone (optional)
18-Hydroxycorticosterone to aldosteroneReactioncyp11_18oxidation
PMID:2256920
Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.
Recombinant human aldosterone synthase converts deoxycorticosterone through corticosterone and 18-hydroxycorticosterone to aldosterone, separating intermediate hydroxylations from terminal oxidation.
PMID:23322723
Structural insights into aldosterone synthase substrate specificity and targeted inhibition.
Human CYP11B2 structural and biochemical data explain substrate recognition, release of reaction intermediates and the additional terminal C18 oxidation relative to CYP11B1.
PMID:32196091
Elaboration of the Corticosteroid Synthesis Pathway in Primates through a Multistep Enzyme.
Ancestral reconstruction and functional assays support retention of multistep activity by primate CYP11B2 and specialization of CYP11B1 after duplication; these experiments do not establish a single mammal-wide duplication.
PMID:1686470
Different isozymes of mouse 11 beta-hydroxylase produce mineralocorticoids and glucocorticoids.
Mouse Cyp11b2 expression in COS-7 cells supports aldosterone synthesis, in contrast to the Cyp11b1 comparator.
PMID:15731365
Homeostatic responses in the adrenal cortex to the absence of aldosterone in mice.
Disruption of mouse Cyp11b2 eliminates detectable circulating aldosterone, confirming the native adrenal requirement alongside direct enzyme evidence.

The specific activity is represented by its descriptive name because no established specific GO identifier is asserted. Requiring only the preceding 18-monooxygenase activity would incorrectly admit enzymes unable to finish aldosterone synthesis.

Annotons

18-Hydroxycorticosterone to aldosterone
cyp11_18oxidation_activity
Participant: Family: CYP11 enzymes with demonstrated aldosterone-synthesis chemistry
Family:
CYP11 enzymes with demonstrated aldosterone-synthesis chemistry The official PANTHER label is not a functional assertion. Selection also requires the stated reaction and the appropriate steroidogenic tissue context. Subfamily members with a different substrate specificity or expression pattern are excluded.
Representative Members: CYP11B2 (human)UniProtKB:P19099 Cyp11b2 (MOUSE)UniProtKB:P15539
Required Function:
18-hydroxycorticosterone oxidase activity

Function

18-hydroxycorticosterone oxidase activity
Substrates: 18-hydroxycorticosterone molecular oxygen reduced ferredoxin
Products: aldosterone

Locations

mitochondrial inner membraneGO:0005743

Terminal oxidative conversion of the C18 hydroxymethyl group to the aldehyde completes aldosterone synthesis. Human CYP11B1 and the selected fish Cyp11c1 do not establish this activity.