Steroid sulfatases

Another enzyme in this class is steryl sulfatase (steroid sulfatase, steryl-sulfate hydrolase, EC 3.1.6.2). The typical substrate of this enzyme is the endogenous metabolite 3/3-hydroxyandrost-5-en-17-one 3-sulfate, but the enzyme also hydrolyzes some related steryl sulfates. 

A number of enzymes known as sulfuric ester hydrolases (EC 3.1.6) are able to hydrolyze sulfuric acid esters. They comprise arylsulfatase (sulfatase, EC 3.1.6.1), steryl-sulfatase (steroid sulfatase, steryl-sulfate sulfohydrolase, arylsulfatase C, EC 3.1.6.2), choline-sulfatase (choline-sulfate sulfohydrolase, EC 3.1.6.6), and monomethyl-sulfatase (EC 3.1.6.16). Whereas mono-methyl-sulfatase is highly specific and does not act on higher homologues, arylsulfatase has a broad substrate specificity and is of particular significance in the hydrolysis of sulfate conjugates of phenols, be they endogenous compounds, drugs, or their metabolites [167-169],... 

C. J. Anderson, L. J. H. Lucas, T. S. Widlanski, Molecular Recognition in Biological Systems Phosphate Esters vs. Sulfate Esters and the Mechanism of Action of Steroid Sulfatases , J. Am. Chem. Soc. 1995,117, 3889-3890. 

A. Purohit, G. J. Williams, N. M. Howarth, B. V. L. Potter, M. J. Reed, Inactivation of Steroid Sulfatase by an Active Site-Directed Inhibitor, Estrone-3-O-sulfamate , Biochemistry 1995, 34, 11508- 11514. 

Arylsulfatase [EC 3.1.6.1 ], also known simply as sulfatase, catalyzes the hydrolysis of a phenol sulfate, thereby producing a phenol and sulfate. This enzyme classification represents a collection of enzymes with rather similar specificities. (1) Steryl-sulfatase [EC3.1.6.2],also referred to as arylsulfatase C and steroid sulfatase, catalyzes the hydrolysis of 3-j8-hydroxyandrost-5-en-17-one 3-sulfate to 3-j8-hydroxyandrost-5-en-17-one and sulfate. The enzyme utilizes other steryl sulfates as substrates. (2) Cere-broside-sulfatase [EC 3.1.6.8], or arylsulfatase A, catalyzes the hydrolysis of a cerebroside 3-sulfate to yield a cerebroside and sulfate. The enzyme will also hydrolyze the galactose 3-sulfate bond present in a number of lipids. In addition, the enzyme will also hydrolyze ascorbate 2-sulfate and other phenol sulfates. 

Recently, dual aromatase-sulfatase inhibiton (DASI) was introduced as a new targeting approach [80]. It is based on the hypothesis that additional inhibition of the steroid sulfatase (STS) should reduce estrone levels signifl-... 

Rationaie for the Use of Steroid Sulfatase Inhibitors in Cancer Treatment... 

Figure 7.14 Inhibition of the steroid sulfatase by fluorinated sulfonamides. " ...

Iversen SD 5-HT and anxiety. Neuropharmacology 23 156-164, 1984 Iwamori M, Moser HW, Kishimoto Y Steroid sulfatase in brain comparison of sulfohydrolase activities for various steroid sulfates in normal and pathological brains, including various forms of metachromatic leukodystrophy. J Neurochem 27 1389-1395, 1976... 

Recessive X-linked ichthyosis (RXLI) steroid sulfatase deficiency STS Xp22.32 308100... 

Recessive X-linked ichthyosis (RXLI) is a dermatological condition that is caused by steroid sulfatase deficiency (STSD), although the mechanism by which the deficiency causes the characteristic scaly skin has not been adequately explained. RXLI is the most common genetic disorder of steroid metabolism, affecting about 1 2000 males. Epstein and workers [16] first demonstrated that serum cholesterol sulfate was elevated in the condition, and this compound has become the preferred analyte for diagnosis. The serum level is more than tenfold greater than normal in the condition. 

Fig. 5.3.7 Disorders that affect the placental/maternal synthesis of estriol and diagnostic analytes for serum and urine. ORD Oxidoreductase deficiency, STS steroid sulfatase deficiency...

Taylor and coworkers have prepared o-fluoromethyl and o-difluoromethyl estrone sulfates82 and shown that these compounds are good substrates for steroid sulfatases.83 The phenol product of hydrolysis of o-fluoromethyl estrone sulfate undergoes heterolytic cleavage to form a quinone methide that inactivates the steroid sulfatase (Scheme 20C).83 The phenol product of hydrolysis of o-difluoromethyl estrone sulfate breaks down first to a quinone methide and then to the o-formyl estrone, which also inactivates the steroid sulfatase.83... 

Tosyliminothiochromone-2-carboxylates 585 are inhibitors of interleukin-1 and are thus useful for the treatment of rheumatoid arthritis, multiple sclerosis, diabetes mellitus, atherosclerosis and septic shock <1995WO9514670>, and thiochromones possessing a sulfamoyloxy side chain at either C-6 or C-7 behave as steroid sulfatase inhibitors < 1999W O9952890>. 

Etiology Defective keratohyaline Steroid sulfatase deficiency Transglutaminase 1-plus several deficiency (other causes) Keratin mutations... 

Shapiro, L. and Weiss, R., X-linked ichthyosis due to steroid sulfatase deficiency, Lancet, 14, 70, 1978. 

Falany, J.L. and Falany, C.N. (2007) Interactions of the human cytosolic sulfotransferases and steroid sulfatase in the metabolism of tibolone and raloxifene. The Journal of Steroid Biochemistry and Molecular Biology, 107, 202-210. 

Andria, G., Ballabio, A., Parenti, G., Di-Maio, S., and Piccirillo, A., Steroid sulfatase deficiency is present in patient with the syndrome Tchthynosis and male hypogonadism and with Rud Syndrome. /. Inherited Metah. Dis. Suppl. 2, 159-160 (1984a). 

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