DHSA
{{chembox
| verifiedrevid = 443680947
| ImageFile = DHSA.svg
| ImageSize = 120px
| IUPACName = 3,4-Dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione
| SystematicName = (3aS,4S,7aS)-4-[2-(2,3-Dihydroxy-6-methylphenyl)ethyl]-7a-methylhexahydro-1H-indene-1,5(4H)-dione
| OtherNames =
|Section1={{Chembox Identifiers
| CASNo=2168-61-8
| CASNo_Ref = {{Cascite|changed|EPA}}
| PubChem=440483
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 15896
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB08542
| KEGG = C04793
| SMILES=CC1=C(C(=C(C=C1)O)O)CCC2C3CCC(=O)C3(CCC2=O)C
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 389410
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI=1S/C19H24O4/c1-11-3-7-16(21)18(23)12(11)4-5-13-14-6-8-17(22)19(14,2)10-9-15(13)20/h3,7,13-14,21,23H,4-6,8-10H2,1-2H3/t13-,14-,19-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YUHVBHDSVLKFNI-NJSLBKSFSA-N
}}
|Section2={{Chembox Properties
| Formula=C19H24O4
| MolarMass=316.39146
| Appearance=
| Density=
| MeltingPt=
| BoilingPt=
| Solubility=
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|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
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3,4-DHSA is an organic compound which is the intermediate product of the metabolism of cholesterol, by the bacteria most commonly responsible for tuberculosis (Mycobacterium tuberculosis).{{PDB|2ZI8}}; {{cite journal | vauthors = Yam KC, D'Angelo I, Kalscheuer R, Zhu H, Wang JX, Snieckus V, Ly LH, Converse PJ, Jacobs WR, Strynadka N, Eltis LD | title = Studies of a Ring-Cleaving Dioxygenase Illuminate the Role of Cholesterol Metabolism in the Pathogenesis of Mycobacterium tuberculosis | journal = PLOS Pathog. | volume = 5 | issue = 3 | pages = e1000344 |date=March 2009 | pmid = 19300498 | pmc = 2652662 | doi = 10.1371/journal.ppat.1000344 | editor1-last = Ramakrishnan | editor1-first = Lalita | doi-access = free }} 3,4-DHSA is an acronym for 3,4-dihydroxy-9,10-seco-androst-1,3,5(10)-triene-9,17-dione, the official name of this substance. It is classified as a secosteroid, since one of the four rings of cholesterol from which it is derived is broken.
3,4-DHSA is a catecholic intermediate (a compound containing an aromatic ring with two adjacent hydroxyl groups) produced by M. tuberculosis during the breakdown of cholesterol. 3,4-DHSA is also produced by other bacteria such as Comamonas testosteroni.{{cite journal | vauthors = Horinouchi M, Kurita T, Yamamoto T, Hatori E, Hayashi T, Kudo T | title = Steroid degradation gene cluster of Comamonas testosteroni consisting of 18 putative genes from meta-cleavage enzyme gene tesB to regulator gene tesR | journal = Biochem. Biophys. Res. Commun. | volume = 324 | issue = 2 | pages = 597–604 |date=November 2004 | pmid = 15474469 | doi = 10.1016/j.bbrc.2004.09.096 }}{{cite journal | vauthors = Horinouchi M, Hayashi T, Kudo T | title = The genes encoding the hydroxylase of 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione in steroid degradation in Comamonas testosteroni TA441 | journal = J. Steroid Biochem. Mol. Biol. | volume = 92 | issue = 3 | pages = 143–54 |date=October 2004 | pmid = 15555908 | doi = 10.1016/j.jsbmb.2004.09.002 | s2cid = 24549812 }}
A particular type of enzyme known as extradiol dioxygenase is responsible for the oxidation and ring opening of 3,4-DHSA to 4,9-DSHA (see metabolic scheme below). M. tuberculosis bacteria that are deficient in this enzyme are less lethal than wild-type bacteria. 3,4-DHSA itself appears to be toxic to the bacteria while the breakdown products of 3,4-DHSA can be used as energy source by the bacteria. Hence blocking the oxidation of 3,4-DHSA by the extradiol dioxygenase enzyme may be useful in the treatment of tuberculosis.
A crystal structure of DHSA in complex with M. tuberculosis iron-dependent extradiol dioxygenase has been determined.
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