Enzyme sulfatase

The first step in the complete biodegradation of primary alcohol sulfates seems to be the hydrolysis to yield alcohol. Sulfatases are able to hydrolyze primary alcohol sulfates. Different authors have isolated and used several sulfia-tase enzymes belonging to Pseudomonas species. The alcohol obtained as a result of the hydrolysis, provided that dehydrogenases have been removed to avoid the oxidation of the alcohol, was identified by chromatography and other methods [388-394]. The absence of oxygen uptake in the splitting of different primary alcohol sulfates also confirms the hydrolysis instead of oxidation [395, 396]. The hydrolysis may acidify the medium and stop the bacterial growth in the absence of pH control [397-399]. 

Recksiek M, T Selmer, T Dierks, B Schmidt, K von Figura (1998) Sulfatases, trapping of the sulfonated enzyme intermediate by substituting the active site formylglycine. J Biol Chem 273 6096-6103. 

Based on the data from animal studies, diisopropyl methylphosphonate is principally excreted in the urine as the metabolite IMPA (Hart 1976 Ivie 1980). Chromatographic behavior of urinary metabolites does not change after the urine is treated with glucuronidase and sulfatase, so there is no conjugation of diisopropyl methylphosphonate or IMPA by microsomal enzymes (Hart 1976). There was minimal excretion of diisopropyl methylphosphonate metabolites in bile (Hart 1976) or in the milk of a lactating cow (<1%) (Palmer et al. 1979). 

The final step is a hydrolyzing step with sulfatase enzymes (E.C. number 3.1.6.1), such as limpet sulfatase, Aerobacter aerogenes sulfatase, Abalone entrail sulfatase, or Helixpomatia sulfatase. This step was suggested to be carried out in a CSTR or fluidized bed reactors, with counter-current flow between the aqueous and the oil phase. A more efficient removal of the sulfate into the aqueous stream is expected to occur in this cross-flow manner. A final separation of the reacting mixture was suggested to obtain sulfur-free product and aqueous enzyme solution for recycle. 

Dierks, T., Schmidt, B., Borissenko, L. V. et al. Multiple sulfatase deficiency is caused by mutations in the gene encoding the human Ca-formylglycine generating enzyme. Cell 113 435-444, 2003. 

There are also numerous enzymes anchored in membranes of the microsomal cell fraction that participate in the metabolism of steroid hormones. Thus, those of the p450 family, which carry out molecular oxidation, or the sulfatases and sulfotransferases, more or less specific to several hormones (Pasqualini et al. 1995). The affinity of steroid hormones for proteins of the membrane (Kd between 10 and 100 nM) is frequently greater than that which some of these enzymes present for their substrates (Luzardo et al. 2000). Therefore, it is unlikely that a part of the proteins of the membrane that bind steroids is in reality enzymes metabolizing these hormones. 

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],... 

Gadler, P. and Faber, K., New enzymes for biotransformations microbial alkyl sulfatases displaying stereo- and enantioselectivity. Trends Biotechnol., 2007, 25, 83. 

In chymotrypsin and other serine proteases the imidazole moiety of histidine acts as a general base not as a nucleophile as is probably the case in the catalysis of activated phenyl ester hydrolysis by (26). With this idea in mind, Kiefer et al. 40) studied the hydrolysis of 4-nitrocatechol sulfate in the presence of (26) since aryl sulfatase, the corresponding enzyme, has imidazole at the active center. Dramatic results were obtained. The substrate, nitrocatechol sulfate, is very stable in water at room temperature. Even the presence of 2M imidazole does not produce detectable hydrolysis. In contrast (26) cleaves the substrate at 20°C. Michaelis-Menten kinetics were obtained the second-order rate constant for catalysis by (26) is 10 times... 

An exo-linker according to Fig. 10.1 must contain an enzyme labile group R, which is recognized and attacked by the biocatalyst Possible combinations could be phenylacetamide/penicillin amidase, ester/esterase, monosaccharide/glycosid-ase, phosphate/phosphatase, sulfate/sulfatase and peptides/peptidases [41]. The following systems have been worked out (Tab. 10.2). 

This enzyme [EC 3.1.6.14] catalyzes the hydrolysis of the 6-sulfate moieties of the A-acetylglucosamine 6-sulfate subunits of heparan sulfate and keratan sulfate. It has been suggested that this enzyme might be identical to A-sulfoglucosamine-6-sulfatase. 

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. 

This enzyme [EC 3.1.6.18], also known as glucuronate-2-sulfatase and chondro-2-sulfatase, catalyzes the hydrolysis of the 2-sulfate groups of the 2-O-sulfo-D-glucuro-nate residues of chondroitin sulfate, heparin, and hepari-tin sulfate. The enzyme does not act on iduronate 2-sulfate residues. 

A major class of enzymes that catalyze hydrolytic cleavage reactions. Examples include esterases, phosphatases, sulfatases, nucleases, glycosidases, peptidases, protein-ases, and amidases. 

This enzyme [EC 3.1.6.13], also known as iduronate-2-sulfate sulfatase and chondroitinsulfatase, catalyzes the... 

AMINOCYCLORRORANE-L-CARBOXYLATE OXIDASE ETIOCHOLANOLONE SULFATASE Evolution of enzyme catalysis,... 

The biologically inactive estrone sulfate (EIS) and dehydro-epiandrosterone-sulfate (DHEAS) are the most abundant circulating estrogenic precursors in the plasma of post-menopausal women [103]. Desulfation of inactive steroid-3-0-sulfates by estrone-sulfatase (STS) plays a key role in the regulation of levels of receptor-active estrogenic steroids (estradiol and androstenediol) in breast cancer cells (Fig. 9). There is strong evidence suggesting that estrone sulfatase (STS) and DHEA-sulfatase are the same enzyme [103]. 

For cells with /1-galactosidase deficiency (GM1 gangliosidosis or Morquio type as well as I-cell disease), the measured enzyme activity will be significantly lower than the true enzyme activity. In addition, cases of multiple sulfatase deficiency will also show low N-acetylgalactosamine-6-sulfatase activity. Therefore, arylsulfatase A or another sulfatase, as well as /1-galactosidase activities should also be determined in case of suspicious results. To exclude poor sample quality, the determination of a-mannosidase is recommended. 

In case of a deficiency of arylsulfatase A, at least one other sulfatase should be measured to exclude multiple sulfatase deficiency (see Chap. 4.1 for the assays of arylsulfatase and other sulfatases). Sulfatide excretion in urine should be measured (see assay below) and/or mutation analysis should to performed to confirm the diagnosis, especially if the clinical symptoms are atypical and in order to exclude a pseudodeficiency of arylsulfatase A. The enzyme should always be measured in the parents to check for the presence of compound heterozygosity of a metachromatic leukodystrophy and a pseudodeficiency allele. This is very important for the interpretation of the results of arylsulfatase A assays, especially when performed in asymptomatic or presymptomatic siblings or in the context of a prenatal diagnosis. Sulfatide should also be measured in case a normal arylsulfatase A activity is found in a patient with symptoms characteristic of (juvenile) metachromatic leukodystrophy. Increased urinary sulfatide excretion is indicative of an activator protein/saposin deficiency (Fig. 4.4.1). 

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