CYP19A1

CYP19A1 (Cytochrome P450 Family 19 Subfamily A Member 1) is a Protein Coding gene. Diseases associated with CYP19A1 include Aromatase Deficiency and Aromatase Excess Syndrome. Among its related pathways are Ovarian Infertility Genes and Androstenedione and testosterone biosynthesis and metabolism p.1. Gene Ontology (GO) annotations related to this gene include iron ion binding and electron transfer activity.

Cytochrome P450 Family 19 Subfamily A Member 1

A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (PubMed:27702664, PubMed:2848247).

Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid (PubMed:20385561).

Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen (PubMed:22773874).

Also displays 2-hydroxylase activity toward estrone (PubMed:22773874).

Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:20385561, PubMed:22773874).

Androgen catabolic process Source: CAFA
Estrogen biosynthetic process Source: Reactome
Female gonad development Source: GO_Central
Positive regulation of estradiol secretion Source: CAFA
Response to estradiol Source: GO_Central
Steroid biosynthetic process Source: ProtInc
Sterol metabolic process Source: Reactome

Endoplasmic reticulum membrane; Microsome membrane

Aromatase excess syndrome (AEXS):
An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females.
Aromatase deficiency (AROD):
A rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries.

Phosphorylated in vitro by PKA and PKG/PRKG1. These phosphorylations inhibit the catalytic activity as measured by estrone synthesis from androstenedione (36% decrease for PKA and 30% for PKG/PRKG1).