Template talk:Estradiol metabolism

Feedback

@Medgirl131: I've made the changes you indicated. If you have any other suggestions/feedback for the background image file, feel free to follow up via email and let me know; if you think it looks good now, I'll start annotating wikitext. Seppi333 (Insert 2¢) 19:23, 8 August 2018 (UTC)

I went ahead and added the annotations since I'd still be using the same approximate coordinates for an annotation regardless of whether I end up swapping one compound with another. The enzyme labels still need to be added; a few minor tweaks the the enzyme annotation coordinates will probably be necessary once that's done. Seppi333 (Insert 2¢) 22:18, 8 August 2018 (UTC)

BRENDA ligand entries for Homo sapiens

Listing what I find on catalyzing enzymes from a database search in this section. Seppi333 (Insert 2¢) 17:39, 10 August 2018 (UTC)

17β-Estradiol → Estrone

Comprehensive search with commentary on isoenzymes: [1]

• EC 1.1.1.35 - [2]
• EC 1.1.1.50 - [3]
• EC 1.1.1.51 - [4]
• EC 1.1.1.62 - [5]: indicates 17β-HSD2, 17β-HSD4, and 17β-HSD5 are involved in this reaction and 17β-HSD1 is the predominant mediator of the reverse reaction.
• EC 1.1.1.239 - [6]
• EC 1.1.1.357 - [7]

Estrone

Comprehensive search with commentary on isoenzymes: [8]

• EC 1.1.1.62 - [9]: indicates 17β-HSD1 is the predominant mediator of Estrone → 17β-Estradiol.
• EC 1.1.1.239 - [10]
• EC 1.1.1.357 - [11]

Estrone sulfation:

• EC 2.8.2.2 [12]
• EC 2.8.2.4: "high activity by SULT1E1, low activity by phenol sulfotransferase SULT1A1, EC 2.8.2.1" (SULT1E1 = EST) - [13]

Estrone glucuronidation:

• EC 2.4.1.17: "glucuronidated by UGT1A3 and HGT1A9" - [14]

@Boghog: This link refers to proteins called "HGT1A9" and "HGT2B7" (you'd need to click the "show all entries" button in the top right corner to see those comments). Are these typos and/or synonyms for UGT1A9 and UGT2B7? Googling "HGT1A9" showed just 7 irrelevant results. Seppi333 (Insert 2¢) 20:02, 10 August 2018 (UTC)

They are almost certainly typos. Follow the links from the Brenda page to 488781 and 488794. Boghog (talk) 20:36, 10 August 2018 (UTC)

Ah, yeah I probably should've just checked the sources; I'm a bit tired from doing so many database searches. Anyway, thanks for pointing that out! Seppi333 (Insert 2¢) 21:42, 10 August 2018 (UTC)

Estrone 2-hydroxylation:

•  Nothing listed – look for pathway in a textbook or review

Estrone 4-hydroxylation:

•  Nothing listed – look for pathway in a textbook or review

Estrone 16α-hydroxylation:

•  Nothing listed – look for pathway in a textbook or review

Estrone sulfate

Desulfation:

• EC 3.1.6.2 (STS / steroid sulfatase) - [15]

16α-Hydroxyestrone

→17-Epiestriol:

•  Nothing listed – look for pathway in a textbook or review

→Estriol:

•  Nothing listed – look for pathway in a textbook or review

→16-Epiestriol:

•  Nothing listed – look for pathway in a textbook or review

Human Metabolome Database entries

Estradiol: [16]

• 17β-HSD1 (listed as gene: HSD17B1) [Catalyzed reactions link: [17]]
• 17β-HSD2 (listed as gene: HSD17B2) [Catalyzed reactions link: [18]]
• 17β-HSD6 (listed as gene: HSD17B6) [Catalyzed reactions link: [19]]
• 17β-HSD7 (listed as gene: HSD17B7) [Catalyzed reactions link: [20]]
• 17β-HSD8 (listed as gene: HSD17B8) [Catalyzed reactions link: [21]]
• 17β-HSD11 (listed as gene: HSD17B11) [Catalyzed reactions link: [22]]
• 17β-HSD12 (listed as gene: HSD17B12) [Catalyzed reactions link: [23]]

Estrone: [24]

CYP450:

• CYP1A1
• CYP1A2
• CYP1B1
• CYP2A7
• CYP2A13
• CYP2B6
• CYP2C8
• CYP2C9
• CYP2C19
• CYP2D6
• CYP2E1
• CYP2F1
• CYP2J2
• CYP2S1
• CYP3A4
• CYP4B1
• CYP4Z1
• CYP19A1C

... I think I'm just going to list "CYP450". Seppi333 (Insert 2¢) 18:32, 10 August 2018 (UTC)

• 16-Epiestriol - no enzymes listed
• 17-Epiestriol - no enzymes listed
• Estriol - metabolized into 16β-Hydroxyestrone by various 17β-HSD isoenzymes. No synthesizing enzymes listed.
• 2-Hydroxyestrone - COMT is listed as a metabolizing enzyme; no synthesizing enzymes listed.
• 4-Hydroxyestrone - no enzymes listed
• 16α-Hydroxyestrone - enzymes are listed but don't indicate reversibility (specifies estriol → 16α-Hydroxyestrone by four 17β-HSD isoenzymes).
• 16β-Hydroxyestrone - enzymes are listed, but as above, the specified reactions don't indicate reversibility (specifies estriol → 16β-Hydroxyestrone by six 17β-HSD isoenzymes, including the same four for 16α-Hydroxyestrone).
  • BRENDA lists 16-hydroxysteroid epimerase as an enzyme the catalyzes the biotransformation of 16α-Hydroxyestrone into 16β-Hydroxyestrone (see this link for details).