Langbahn Team – Weltmeisterschaft

6β-Hydroxycortisol

6β-Hydroxycortisol
Names
IUPAC name
(6R,8S,9S,10R,11S,13S,14S,17R)-6,11,17-trihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one
Other names
6-beta-hydroxycortisol, 6-beta-hydroxy-cortisol, 6beta-hydroxycortisol, 6beta-hydroxy-cortisol, 6β-OH-cortisol, 6beta-OH-cortisol, 6β-OHF, 6beta-OHF, 6β,11β,17,21-tetrahydroxypregn-4-ene-3,20-dione, (6β,11β)-6,11,17,21-tetrahydroxypregn-4-ene-3,20-dione, 6β,11β,17α,21-tetrahydroxypregn-4-ene-3,20-dione
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
UNII
  • InChI=1S/C21H30O6/c1-19-5-3-11(23)7-14(19)15(24)8-12-13-4-6-21(27,17(26)10-22)20(13,2)9-16(25)18(12)19/h7,12-13,15-16,18,22,24-25,27H,3-6,8-10H2,1-2H3/t12-,13-,15+,16-,18+,19-,20-,21-/m0/s1
    Key: GNFTWPCIRXSCQF-UJXAPRPESA-N
  • InChI=1S/C21H30O6/c1-19-5-3-11(23)7-14(19)15(24)8-12-13-4-6-21(27,17(26)10-22)20(13,2)9-16(25)18(12)19/h7,12-13,15-16,18,22,24-25,27H,3-6,8-10H2,1-2H3/t12-,13-,15+,16-,18+,19-,20-,21-/m0/s1
  • C1[C@@]2([C@@]([C@@]3(C([C@@H]1O)=CC(CC3)=O)C)([C@H](C[C@@]4([C@@](CC[C@@]24[H])(O)C(CO)=O)C)O)[H])[H]
Properties
C21H30O6
Molar mass 378.46
Melting point 239-241°C
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

6β-Hydroxycortisol is an endogenous steroid. In humans, it is a metabolite of cortisol produced by cytochrome p450-3A monooxygenases, mainly, 6β-hydroxysteroid dehydrogenase (CYP3A4).[2][3][4][5] 6β-hydroxycortisol is used as a biomarker of 6β-hydroxysteroid dehydrogenase (CYP3A4) activity.[6] Drugs that induce CYP3A4 may accelerate cortisol clearance, by accelerating cortisol conversion to 6β-hydroxycortisol,[7][8] and vice versa: drugs that inhibit CYP3A4 can slow down cortisol clearance, as they reduce the conversion of cortisol to 6β-hydroxycortisol.

Biological role

Although the exact role of 6β-hydroxycortisol in the human body is not fully understood, it is believed to play an important role in the metabolism and clearance of cortisol.

6β-hydroxycortisol is a metabolite of cortisol: the enzyme 6β-hydroxysteroid dehydrogenase (CYP3A4) catalyzes the formation of 6β-hydroxycortisol from cortisol in the liver and other tissues; the resulting 6β-hydroxycortisol is excreted in urine.

6β-hydroxycortisol levels may be affected by drugs that induce or inhibit CYP3A4, thereby affecting cortisol metabolism.

Clinical significance

In normal metabolism, the level of 6β-hydroxycortisol is regulated by the activity of 6β-hydroxysteroid dehydrogenase (CYP3A4) and other enzymes involved in cortisol metabolism. Abnormal 6β-hydroxycortisol levels may indicate underlying metabolic abnormalities such as Cushing's syndrome, a condition characterized by overproduction of cortisol, or Addison's disease, a condition characterized by underproduction of cortisol.

6β-hydroxycortisol is being investigated as a potential biomarker of 6β-hydroxysteroid dehydrogenase (CYP3A4) activity and may have diagnostic or prognostic value in certain diseases. Understanding the role of 6β-hydroxycortisol in human physiology and disease may lead to the development of new diagnostic and therapeutic strategies.

In addition to cortisol, many drugs are also metabolized by CYP3A4. Examples of drugs metabolized by CYP3A4 are statins (used to lower cholesterol levels), benzodiazepines (used to treat anxiety and insomnia), calcium channel blockers (used to treat high blood pressure), etc. By measuring 6β-hydroxycortisol levels in clinical trials, researchers can assess whether certain drugs affect the activity CYP3A4 which is needed to metabolize other drugs and cortisol. Such observations bring knowledge about potentially dangerous drug interactions and help prevent life-threatening conditions in people who have impaired cortisol synthesis. One example of such dangerous interaction are modafinil (a stimulant) and hydrocortisone (an exogenous cortisol). Modafinil has the ability to induce the activity of CYP3A4 which is involved in hydrocortisone clearance and consequently decrease the bioavailability of hydrocortisone.[7]

See also

References

  1. ^ "CAS Common Chemistry 6β-Hydroxycortisol Compound Properties". Archived from the original on 21 November 2021. Retrieved 21 November 2021.
  2. ^ "PubChem 6beta-Hydroxycortisol compound summary". Archived from the original on 20 November 2021. Retrieved 21 November 2021.
  3. ^ Luceri F, Fattori S, Luceri C, Zorn M, Mannaioni P, Messeri G (December 2001). "Gas chromatography-mass spectrometry measurement of 6beta-OH-cortisol/cortisol ratio in human urine: a specific marker of enzymatic induction". Clin Chem Lab Med. 39 (12): 1234–9. doi:10.1515/CCLM.2001.198. PMID 11798083. S2CID 12216877.
  4. ^ Finken MJ, Andrews RC, Andrew R, Walker BR (September 1999). "Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11beta-hydroxysteroid dehydrogenases". J Clin Endocrinol Metab. 84 (9): 3316–21. doi:10.1210/jcem.84.9.6009. PMID 10487705.
  5. ^ Huang FR, Zhou C, Zhang XY, Shen Y, Zhang HW, Wang YQ, Sun LN (October 2021). "Impact of CYP2C19 genotype on voriconazole exposure and effect of voriconazole on the activity of CYP3A in patients with haematological malignancies". Xenobiotica. 51 (10): 1199–1206. doi:10.1080/00498254.2021.1969481. PMID 34402388. S2CID 237150260.
  6. ^ Lutz U, Bittner N, Ufer M, Lutz WK (January 2010). "Quantification of cortisol and 6 beta-hydroxycortisol in human urine by LC-MS/MS, and gender-specific evaluation of the metabolic ratio as biomarker of CYP3A activity". J Chromatogr B. 878 (1): 97–101. doi:10.1016/j.jchromb.2009.11.023. PMID 19959402.
  7. ^ a b Aquinos BM, García Arabehety J, Canteros TM, de Miguel V, Scibona P, Fainstein-Day P (2021). "[Adrenal crisis associated with modafinil use]". Medicina (B Aires) (in Spanish). 81 (5): 846–849. PMID 34633961.
  8. ^ Peng CC, Templeton I, Thummel KE, Davis C, Kunze KL, Isoherranen N (June 2011). "Evaluation of 6β-hydroxycortisol, 6β-hydroxycortisone, and a combination of the two as endogenous probes for inhibition of CYP3A4 in vivo". Clin Pharmacol Ther. 89 (6): 888–95. doi:10.1038/clpt.2011.53. PMC 3481835. PMID 21490593.
Quelle: https://en.wikipedia.org/wiki/6%CE%B2-Hydroxycortisol