DHSA

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).^[1] 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.

DHSA

Names
IUPAC name 3,4-Dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione
Systematic IUPAC name (3aS,4S,7aS)-4-[2-(2,3-Dihydroxy-6-methylphenyl)ethyl]-7a-methylhexahydro-1H-indene-1,5(4H)-dione
Identifiers
CAS Number	2168-61-8 N[EPA]
3D model (JSmol)	Interactive image
ChEBI	CHEBI:15896 Y
ChemSpider	389410 Y
DrugBank	DB08542 Y
KEGG	C04793
PubChem CID	440483
CompTox Dashboard (EPA)	DTXSID701028828
InChI InChI=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 Y Key: YUHVBHDSVLKFNI-NJSLBKSFSA-N Y
SMILES CC1=C(C(=C(C=C1)O)O)CCC2C3CCC(=O)C3(CCC2=O)C
Properties
Chemical formula	C19H24O4
Molar mass	316.39146
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

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.^[1] 3,4-DHSA is also produced by other bacteria such as Comamonas testosteroni.^[2][3]

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.^[1]

A crystal structure of DHSA in complex with M. tuberculosis iron-dependent extradiol dioxygenase has been determined.^[1]

Synthesis and degradation of 3,4-DHSA.^[1]

References

1. PDB: 2ZI8​; Yam KC, D'Angelo I, Kalscheuer R, Zhu H, Wang JX, Snieckus V, Ly LH, Converse PJ, Jacobs WR, Strynadka N, Eltis LD (March 2009). Ramakrishnan L (ed.). "Studies of a Ring-Cleaving Dioxygenase Illuminate the Role of Cholesterol Metabolism in the Pathogenesis of Mycobacterium tuberculosis". PLOS Pathog. 5 (3): e1000344. doi:10.1371/journal.ppat.1000344. PMC 2652662. PMID 19300498.
2. Horinouchi M, Kurita T, Yamamoto T, Hatori E, Hayashi T, Kudo T (November 2004). "Steroid degradation gene cluster of Comamonas testosteroni consisting of 18 putative genes from meta-cleavage enzyme gene tesB to regulator gene tesR". Biochem. Biophys. Res. Commun. 324 (2): 597–604. doi:10.1016/j.bbrc.2004.09.096. PMID 15474469.
3. Horinouchi M, Hayashi T, Kudo T (October 2004). "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". J. Steroid Biochem. Mol. Biol. 92 (3): 143–54. doi:10.1016/j.jsbmb.2004.09.002. PMID 15555908. S2CID 24549812.