Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
Metalloprotease
G-alpha
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Transporter
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
DNA
RNA
Compound
Inorganic ion
Predicted metabolite or user's structure
Reaction
Generic receptor
GPCR
Receptors with enzyme activity
Mitochondria
EPR
Golgi
Nucleus
Lysosome
Peroxisome
Cytoplasm
Extracellular

Normal process
Pathological process
Binding
Cleavage
Covalent modifications
Phosphorylation
Dephosphorylation
Transformation
Transport
Catalysis
Transcription regulation
MicroRNA binding
Competition
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Estrogen biosynthesis


Log In to Post A Comment

Estrogen biosynthesis

Estrogen biosynthesis.

The biosynthesis of estrogen is initiated by the synthesis of Androstenedione,19-carbon steroid hormone, from cholesterol. Then this compound is converted to estrogensEstrone or Estradiol, either immediately or through Testosterone,which may also be derived from cholesterol.

Reduction of Androstenedione to Testosterone requires Hydroxysteroid(17-beta) dehydrogenase 2 ( HSD17B2 ) [1], [2] andHydroxysteroid (17-beta) dehydrogenase 3 ( HSD17B3 ) [3], [4], [5]. The reverse reaction, oxidation of Testosterone at17-position to form Androstenedione, is catalyzed by monooxygenase CytochromeP450, family 2, subfamily C, polypeptide 19 ( CYP2C19 ) [6].

Androstenedione undergoes a three-step A-ring aromatization to Estronecatalyzed by monooxyganases: aromatase Cytochrome P450, family 19, subfamily A,polypeptide 1 ( CYP19 ) [7] and Cytochrome P450, family 11, subfamilyB, polypeptide 1 ( CYP11B1 ) [8]. The first intermediate reaction isthe formation of 19-Hydroxyandrostenedione [9], which then isconverted to Androst-4-en-3,17,19-trione [9], [7]followed by oxidation to Estrone [9], [7].

Another pathway of Estrone biosynthesis is oxidation of17-alpha-Estradiol by Estradiol 17a-dehydrogenase ( 1.1.1.148 ) [10].

Aromatase CYP19 also catalyzes oxidation of Testosterone toEstradiol [11], [7]. The first step is formation of19-Hydroxytestosterone [12], which in turn is oxidized to19-Oxotestosterone [11], and then to Estradiol [13],[11], similar to Androstenedione catabolism to Estrone.

Another steroid substrate, which undergoes a CYP19 -catalyzed three-steparomatization, is 16alpha-Hydroxyandrostenedione [14], [15]. The final product of that oxidation is 16alpha-Hydroxyestrone.

Interconversion of Estradiol and Estrone requires Hydroxysteroid(17-beta) dehydrogenases 1 ( HSD17B1 ) [16], 7 ( HSD17B7 )[17] and 8 ( HSD17B8 ) [18].