Aromatase

From Citizendium, the Citizens' Compendium
Jump to: navigation, search
This article is a stub and thus not approved.
Main Article
Talk
Related Articles  [?]
Bibliography  [?]
External Links  [?]
Citable Version  [?]
 
This editable Main Article is under development and not meant to be cited; by editing it you can help to improve it towards a future approved, citable version. These unapproved articles are subject to a disclaimer.
(CC) Image: David E. Volk
Human placental aromatase bound to ligands androstenedione (cyan) and heme (yellow). Coordinates obtained from the RCSB Protein Data Bank (3EQM).

Aromatase, the 503-amino acid long protein product of the CYP19A1 gene on chromosome 15q21.1, is an enzyme that removes the C-19 methyl group via two oxidation steps and oxidizes the 3- and 17-positions of androgenic steroids to convert them into estrogenic steroids (estrogen). It oonverts androstenedione, testosterone and 16-hydroxytestosterone into estrogen, 17-estradiol and 17-,16--estriol, respectively.[1], [2], [3] Because some tumors are estrogen-sensitive, aromatase inhibitors are sometimes used to treat cancer, mostly in post-menopausal women because aromatase inhibitors do not block estrogen synthesis in the ovaries.

Structure and function

(CC) Image: David E. Volk

Aromatase is the only enzyme in vertibrates that is capable of synthesizing all of the estrogen steroids from androgens, and has therefore been of great interest as a treatment for estrogen-sensitive tumors. Despite decades of research into aromatase, its structure was only determined in 2009. The structure of human placental aromatase cytochrome P450 bound to ligands androstenedione (cyan) and heme (yellow) was determined by x-ray crystallography.[4]



References

  1. (1974) "Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione". J. Biol. Chem. 249: 5364-5372.
  2. (1994) "Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis". Endocr. Rev 15: 342-355.
  3. (1998) "Aromatase inhibitors". Crit. Rev. Biochem. Mol. Biol. 33: 375-405.
  4. (January 8) "Structural Basis for Androgen Specificity and Estrogen Synthesis in Human Aromatase". Nature 457: 219-225. DOI:10.1038/nature07614. Research Blogging.