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PubMed2003

Prednisolone 21-sulfate sodium: a colon-specific pro-drug of prednisolone.

Prednisolone 21-sulfate sodium (PDS) was synthesized as a colon-specific pro-drug of prednisolone with the expectation that it would be stable and non-absorbable in the upper intestine and release prednisolone by the action of sulfatase once it was delivered to the colon. In-vitro/in-vivo properties were investigated using rats as test animals. PDS was chemically stable at pH 1.2, 4.5, 6.8 and 8.0, and the apparent partition coefficient was 0.11 in 1-octanol/pH 6.8 buffer solution at 37 degrees C. PDS was stable on incubation with the contents of the stomach or small intestine. When PDS (0.1 mg equiv. of prednisolone) was incubated with the caecal contents (0.05 g), prednisolone was produced to a maximum 54% of the dose in 6 h and decreased thereafter, which suggested that reduction of the A ring took place in addition to the hydrolysis by sulfatase. After oral administration of PDS, a small portion of prednisolone was recovered from the cecal contents but not from the small intestine. Neither PDS nor prednisolone was detected in the plasma, suggesting that absorption of PDS is limited. The data demonstrate that the sulfate ester can serve as a novel colon-specific pro-moiety by limiting the absorption of the pro-drug in the upper intestine and releasing the active compound by the action of microbial sulfatase in the colon.

Administration, Oral↗
PubMed1990

[Study on the local estrogen biosynthesis in human uterine leiomyoma].

The growth of uterine leiomyoma is regulated not only by the estrogen levels in blood, but also by estrogen production in the tumor itself. In this study, we investigated both the estrone formation (estrone sulfatase activity) and the transformation from estrone to estrone sulfate (estrone sulfotransferase activity) in human leiomyoma tissue. We compared them with those in the myometrium and endometrial tissues overlying and opposite a uterine leiomyoma node. We also measured the tissue concentrations of estrone, estradiol and estrone sulfate. Estrone sulfatase activity in the uterine leiomyoma was 0.49 +/- 0.08 nmol/h/mg protein (Mean +/- SE), and was lower than that in the myometrial tissue (0.76 +/- 0.09). Moreover, the enzyme activity was higher in the endometrium overlying the leiomyoma node (2.62 +/- 0.29) than in the endometrium opposite to it (2.10 +/- 0.24). On the other hand, estrone sulfotransferase activity in the myoma (20.2 +/- 2.4 pmol/h/mg protein) was higher than in myometrial tissue (16.7 +/- 2.3). The concentrations of estrone and estradiol in leiomyoma tissue were lower than in the tissues surrounding the leiomyoma. The tissue concentration of estrone sulfate was higher in leiomyoma tissues. These results suggest that estrone sulfate is hydrolyzed mainly by estrone sulfatase in the endometrium and myometrium surrounding leiomyoma nodes and the estrone formed may affect the growth of leiomyoma.

Adult↗
PubMed1981

Metabolism of fatty acid-labeled cerebroside sulfate in cultured cells from controls and metachromatic leukodystrophy patients. Use in the prenatal identification of a false positive fetus.

Metachromatic leukodystrophy is the name given to a group of diseases in patients having a deficiency of CS sulfatase activity. The diagnosis usually can be made by using leukocytes, urine, and cultured skin fibroblasts. The low level of enzyme activity can be measured with an artificial substrate, NCS, or suitably labeled CS. In a number of families, healthy carriers of this autosomal recessive disease have been found to have enzyme levels near those of affected patients. We prepared (14)C-stearic acid-labeled CS and studied its metabolism in cultured human cells from patients and controls, In vitro, CS sulfatase requires bile salts to stimulate the enzymatic reaction. The (14)C-CS also can be added to the medium on cultured cells, and its metabolism in the cells can be followed without the addition of bile salts. A child with late infantile MLD was identified by studies on urine and leukocytes. Studies on leukocytes from the parents revealed a very low enzyme level in the father (false positive) and a typical carrier level in the mother. A pregnancy in this family was monitored, and in vitro studies on cultured AFC revealed low CS and NCS sulfatase levels. However, the addition of (14)C-CS to the culture medium revealed normal metabolism in these cells. An unaffected fetus was predicted on the basis of the cell feeding studies. The couple elected to abort this pregnancy, and studies on the fetus confirmed it would not have been affected with MLD.

Amniotic Fluid↗
PubMed1997

Molecular basis of Zellweger syndrome, beta-ketothiolase deficiency and mucopolysaccharidoses.

1. A human peroxisome assembly factor-1 (PAF-1) complementary DNA has been cloned that restores the morphological and biochemical abnormalities (including defective peroxisome assembly) in fibroblasts from a patient with group F Zellweger syndrome. The cause of the syndrome in this patient was a point mutation that resulted in the premature termination of PAF-1. The homozygous patient apparently inherited the mutation from her parents, each of whom was heterozygous for that mutation. Furthermore, we cloned and characterized the rat and human cDNAs for peroxisome-assembly factor-2 (PAF-2), which restores peroxisomes of the complementary group C Zellweger cells, by functional complementation, and identified two pathogenic mutations in the PAF-2 gene in two patients. 2. Seventeen mutations have been identified in 13 mitochondrial acetoacetyl-CoA thiolase-deficient patients. 3. We purified N-acetylgalactosamine-6-sulfate (GalNAc6S) sulfatase and cloned the full-length cDNA of human N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The gene encoding GalNAc6S sulfatase has been localized by fluorescence in situ hybridization to chromosome 16q24, and the entire genomic gene structure has been characterized. About 40 different GALNS gene mutations have been identified in the patients with mucopolysaccharidosis IV A.

Acetyl-CoA C-Acyltransferase↗
PubMed1994

Programmed expression of cholesterol sulfotransferase and transglutaminase during epidermal differentiation of murine skin development.

To clarify the role of cholesterol sulfate (CS) in the process of epidermal differentiation in vivo, we investigated the concentration of CS and the specific activities of cholesterol sulfotransferase (CST), cholesterol sulfate sulfatase (CS sulfatase) and epidermal transglutaminase (ETG) in murine skin in the pre- and postnatal periods. In the skin at day 14 of gestation, CS was not detected with TLC and the specific activities of all the enzymes were low. However, concomitant with the formation of the multilayered structure of the epidermis (at day 16), the specific activities of CST steeply increased. Although the insoluble CS sulfatase in the microsomal fraction remained at a relatively constant level, the soluble CST in the cytosol fraction showed a 6-fold increase from day 14 to day 16, and the activity decreased continuously in the following period, reaching one forty-sixth of the maximum level at 4-months-old mice. Reflected by the increase in activity, CS was detected in fetal skin at day 15, and the concentration in epidermis significantly increased during the gestation period, reaching maximum level at day 17. Furthermore, the changes in the concentration of cholesterol sulfate were identical with those of N-(O-linoleoyl)-omega-hydroxy fatty acyl sphingosine and its glucosyl derivative in the epidermis. On the other hand, the specific activity of ETG increased after birth. Thus, the activation of CST and ETG was shown to occur separately in association with the formation of the multilayered structure and thickening of the stratum corneum, respectively.

Animals↗
PubMed2004

Development of a novel analytical method for determination of chondroitin sulfate using an in-capillary enzyme reaction.

A novel analytical method for determination of total amount of chondroitin sulfate (CS) based on its conversion to desulfated chondro-disaccharide via an enzyme-catalyzed reaction, was developed. Using the in-capillary enzyme reaction, the method was also applied to the successful construction of an on-line analytical system. Within this system, electrophoretic migration was used to mix zones containing the enzyme mixture (chondroitinase ABC, chondro-4-sulfatase, chondro-6-sulfatase and 2-o-sulfatase) and the substrate (CS). The reaction was then allowed to proceed in the presence of a weak electric field and, finally, the product (desulfated chondro-disaccharide) of enzyme reaction migrated to the detector under the influence of an applied electric field. A polyvinyl alcohol-coated capillary was used to reduce protein adsorption. Desulfated chondro-disaccharide was successfully migrated toward the anode in 10 mM Tris-acetate buffer (pH 7.0) under reversed polarity and detected at 232 nm. The established method was validated and demonstrated to be applicable in the determination of total amount of CS in a commercial ophthalmic solution. No interference from the formulation excipients was observed. Good linearity was obtained, with correlation coefficients above 0.999. Recoveries and precisions ranged from 100.0 to 100.5%, and from 0.2 to 0.6% of the relative standard deviation, respectively. Good agreement was obtained between the established method and traditional photometric method based on carbazole reaction. In this study, application of the method to disaccharide compositional analysis was also performed.

Chondroitin Sulfates↗
PubMed2005

Mucopolysaccharidosis type II in females: case report and review of literature.

Mucopolysaccharidosis type II (Hunter disease, iduronate-2-sulfatase deficiency) was diagnosed in a 4-year-old female by demonstrating low iduronate-2-sulfatase activity both in leukocytes and fibroblasts and by the presence of a novel, complex rearrangement of the iduronate-2-sulfatase gene in heterozygous form. Mucopolysaccharidosis type II is inherited in an X-linked recessive manner and consequently females are rare. The disease phenotype in this case is due to complete unilateral inactivation of the nonmutant paternal X chromosome of the patient. The case presented here underscores the fact that a diagnosis of mucopolysaccharidosis type II should be suspected in any female who presents with the relevant clinical symptoms.

Child, Preschool↗
PubMed1987

Steroid synthetic and prostaglandin metabolizing activity is present in different cell populations from human fetal membranes and decidua.

We examined whether different cell subpopulations from human fetal membranes and decidua produce steroids (estrone and progesterone) and metabolize prostaglandins (prostaglandin F2 alpha to 13, 14-dihydro-15-keto-prostaglandin F2 alpha and if these changed with labor. Amnion, chorion, and decidua were obtained at elective cesarean section at term or at spontaneous labor. Cells were dispersed with collagenase and separated by density on discontinuous Percoll gradients. At cesarean section there was a major broad band of cells from amnion and chorion. This band contained most of the estrone sulfatase (estrone sulfate to estrone) activity. The 3 beta-hydroxysteroid dehydrogenase (pregnenolone to progesterone conversion) and prostaglandin F2 alpha metabolizing activities were present in these cells and those that migrated at greater Percoll densities. Amnion and chorion obtained after spontaneous labor had two major bands of cells. Estrone sulfatase was present in cells from both hands, whereas progesterone output from pregnenolone and prostaglandin F2 alpha metabolism predominated in the second band of cells with greater density. This pattern was particularly apparent in chorion. Dispersed cells from decidua tended to migrate throughout the gradient. In general, estrone sulfate to estrone conversion predominated in lighter cells whereas progesterone output from pregnenolone and prostaglandin F2 alpha metabolism predominated in cells of greater density. The output of progesterone from pregnenolone was significantly lower in cell preparations from chorion and decidua at spontaneous labor compared with cesarean section. We conclude that human amnion, chorion, and decidua contain distinct cell subpopulations based on Percoll migration and that in the membranes these change between cesarean section and spontaneous labor. Partial separation of estrone sulfatase from 3 beta-hydroxysteroid dehydrogenase and prostaglandin F2 alpha metabolizing activities has been demonstrated, which raises the possibility of paracrine interactions in vivo.

Cells, Cultured↗
PubMed1986

Heparin trisaccharides with nonreducing 2-amino-2-deoxy-alpha-D-glucopyranosyl end-groups suitable as substrates for catabolic enzymes.

Heparin trisaccharides having the sequence O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-alpha-L- idopyranosyluronic acid-(1----4)-2,5-anhydro-D-[1-3H]mannitol have been prepared, as substrate models for studying sulfatases of heparan sulfate catabolism, by alpha-L-iduronidase cleavage of previously reported heparin tetrasaccharides, with additional chemical and enzymic modification as required. Three series are described, including isomeric sulfate esters of that trisaccharide with no N-substituent, with N-acetyl substitution, and with N-sulfate substitution. New features of the substrate specificity of the hydrolases used, including iduronate sulfatase, alpha-L-iduronidase, glucosamine 6-sulfate sulfatase, and heparin sulfamidase, were observed, and simple procedures for partial purification of these hydrolases are reported. The structures assigned to the trisaccharides are supported by the mode of preparation, reactions, regularities in electrophoretic behavior, and identities of the products of deamination.

Carbohydrate Sequence↗
PubMed2002

Cutaneous androgen metabolism: basic research and clinical perspectives.

The skin, especially the pilosebaceous unit composed of sebaceous glands and hair follicles, can synthesize androgens de novo from cholesterol or by locally converting circulating weaker androgens to more potent ones. As in other classical steroidogenic organs, the same six major enzyme systems are involved in cutaneous androgen metabolism, namely steroid sulfatase, 3beta-hydroxy-steroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, steroid 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase, and aromatase. Steroid sulfatase, together with P450 side chain cleavage enzyme and P450 17-hydroxylase, was found to reside in the cytoplasm of sebocytes and keratinocytes. Strong steroid sulfatase immunoreactivity was observed in the lesional skin but not in unaffected skin of acne patients. 3beta-hydroxysteroid dehydrogenase has been mainly immunolocalized to sebaceous glands, with the type 1 being the key cutaneous isoenzyme. The type 2 17beta-hydroxysteroid dehydrogenase isoenzyme predominates in sebaceous glands and exhibits greater reductive activity in glands from facial areas compared with acne nonprone areas. In hair follicles, 17beta-hydroxysteroid dehydrogenase was identified mainly in outer root sheath cells. The type 1 5alpha-reductase mainly occurs in the sebaceous glands, whereby the type II isoenzyme seems to be localized in the hair follicles. 3alpha-hydroxysteroid dehydrogenase converts dihydrotestosterone to 3alpha-androstanediol, and the use of 3alpha-androstanediol glucuronide serum level to reflect the hyperandrogenic state in hirsute women may be a reliable parameter, especially for idiopathic hirsutism. In acne patients it is still controversial if 3alpha-androstanediol glucuronide or androsterone glucuronide could serve as suitable serum markers for measuring androgenicity. Aromatase, localized to sebaceous glands and to both outer as well as inner root sheath cells of anagen terminal hair follicles, may play a "detoxifying" role by removing excess androgens. Pharmacologic development of more potent specific isoenzyme antagonists may lead to better clinical treatment or even prevention of androgen-dependent dermatoses.

Androgens↗
PubMed1980

Experimental animal model for mucopolysaccharidosis: suramin-induced glycosaminoglycan and sphingolipid accumulation in the rat.

Intracerebral injection of the trypanocidal drug suramin in rats caused the formation of membranous neuronal and neuroglial inclusions. Here we show that intravenous administration suramin, 500 mg/kg, to 2-month-old rats causes a 5- to 8-fold increase of glycosaminoglycan concentration in the liver within 10 days and a 6-fold increase in urinary glycosaminoglycan excertion. The excess glycosaminoglycans consist of heparan sulfate and dermatan sulfate. Intracerebral injection of 250 micrograms of suramin results in a small increase of glycosaminoglycan and larger increase of ganglioside GM2, GM3, and GD3 concentrations in the treated region of the brain. The activities of the lysosomal enzymes iduronate sulfatase, beta-glucuronidase, and hyaluronidase in the liver of the suramin-treated mature rats were consistently decreased, whereas those of alpha-L-iduronidase, heparan N-sulfatase, arylsulfatase B, and others were considerably increased. The activity of iduronate sulfatase was completely inhibited in vitro by suramin at concentrations of 50 microM or higher. The activity of beta-glucuronidase was also strongly inhibited by low concentrations of suramin, but this inhibition was partially decreased at higher concentrations of the drug. The inhibition of both enzymes by suramin was noncompetitive. The suramin-treated rat may be a useful experimental animal model of mucopolysaccharidosis.

Age Factors↗
PubMed1998

Arylsulfatase from Klebsiella pneumoniae carries a formylglycine generated from a serine.

Eukaryotic sulfatases share an unusual posttranslational protein modification, which converts a cysteine into alpha-formylglycine. The alpha-formylglycine is essential for the catalytic activity. Klebsiella pneumoniae expresses an inducible arylsulfatase for which the DNA predicts a serine at the position occupied by the alpha-formylglycine residue in eukaryotic sulfatases. Structural analysis showed that the majority of the arylsulfatase polypeptides from K. pneumoniae carries the alpha-formylglycine, whereas the remaining arylsulfatase polypeptides contain the predicted serine residue. This demonstrates the evolutionary conservation between prokaryotes and eukaryotes of this novel protein modification that so far has been found only in sulfatases. alpha-Formylglycine in Klebsiella is generated from a serine and not from a cysteine as in eukaryotes.

Alanine↗
PubMed2006

Localization of a lysosomal enzyme in platelets from patients with the White platelet syndrome.

The White platelet syndrome (WPS) is an autosomal dominant platelet disorder. Platelet structural abnormalities include the presence of Golgi complexes in up to 13% of their cells, frequently accompanied by centrioles, deficient numbers or absent alpha granules in 30-40% of their platelets and masses of dense tubular system (DTS) channels often forming areas of cytoplasmic sequestration. The degradation of cytoplasm and organelles in the sequestered areas suggested the possibility that hydrolytic enzymes remained in the DTS and were being transferred to sequestration vacuoles. The present study has used ultrastructural cytochemistry to localize the sites of a lysosomal enzyme, aryl sulfatase, in normal and WPS platelets. Enzyme reaction product, lead sulfide, was localized to lysosomal organelles in normal platelets, and only in rare examples appeared in the DTS. Aryl sulfatase activity was found in the Golgi complexes, a few lysosomes, much of the DTS and areas of cytoplasmic sequestration in WPS platelets. The findings indicate that aryl sulfatase, and, most likely, proteins destined for alpha granules in WPS platelets are not completely transferred from the endoplasmic reticulum to Golgi complexes, then to Golgi vesicles and finally to lysosomal and alpha granules in the parent cell before the platelets are delivered to the circulation.

Arylsulfatases↗
PubMed1993

Mutagenicity of the bile of dogs with an experimental model of an anomalous arrangement of the pancreaticobiliary duct.

To learn the reasons for the high incidence of biliary carcinoma in patients with anomalous arrangement of the pancreaticobiliary duct (APBD) mutagenicity of the bile of APBD-modeled dogs that had received a dorsal pancreatico-cholecystostomy was assayed by the Ames Salmonella mutation test. The bile from two out of 18 APBD dogs was mutagenic for Salmonella typhimurium strain TA98 under the condition of metabolic activation by rat liver S9 fraction, while the bile from 17 normal dogs was not mutagenic. Furthermore, the bile from five APBD dogs i.p. administered 1-nitropyrene (1-NP), which is a typical environmental mutagen, was more mutagenic for strain TA98 than that from 1-NP-treated normal dogs. The bile from the APBD dogs had very high amylase activity, indicating that the bile contained pancreatic juice as a result of the pancreatico-cholecystostomy. When pancreatic juice from a normal dog was added to the bile from 1-NP-treated normal dogs, mutagenicity of the bile increased 1.6- to 2.0-fold. Furthermore, sulfatase increased the mutagenic activity of the bile in the presence of the pancreatic juice. HPLC revealed that the bile from a 1-NP-treated APBD dog contained mutagenic 1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, while bile from a 1-NP-treated normal dog did not contain these deconjugated products. The pancreatic juice from a normal dog had very high gamma-glutamyltransferase (GGT) and aminopeptidase activities and low sulfatase activity, but it had no beta-glucuronidase activity. In addition, the bacteria that easily infect the biliary duct of APBD dogs, Escherichia coli, Klebsiella, Enterobacter and Proteus, had high beta-glucuronidase activity. In particular, Klebsiella showed a very high sulfatase activity. These results suggest that pancreatic juice enzymes and bacteria infecting the biliary duct deconjugate the detoxified mutagens in the bile and induce mutagenicity of the bile from APBD dogs or APBD patients.

Anastomosis, Surgical↗
PubMed1986

Heterogeneity of Morquio disease.

Further clinical heterogeneity of Morquio disease, mucopolysaccharidosis IV (MPS IV), is delineated by the observation of a 30-year-old man with unusually mild clinical manifestations. He is 156 cm tall, has comparatively mild skeletal abnormalities and fine corneal deposits. Keratosulfaturia is absent. N-Acetylgalactosamine-6-sulfate (GalNAc-6-S) sulfatase (E.C. 3.1.6.-) was markedly reduced in his fibroblasts. The residual enzyme activity exhibited a pH profile comparable to that of patients with the "classical" form of the disorder. From our observation and a review of the literature it is concluded that Morquio disease can be divided in several subgroups: besides the severe ("classical") type A there exist an intermediate and a mild form that are also caused by a GalNAc-6-S sulfatase deficiency. A late-onset variant of Morquio disease, which is due to a deficiency of beta-galactosidase, has been classified as type B. In addition, patients with mild manifestation of the disease and normal activities in fibroblasts of GalNAc-6-S sulfatase and beta-galactosidase have been observed (type C). The genetic nature of the broad clinical variability of Morquio disease is incompletely understood: it is partially caused by different enzyme defects. Other factors thought to influence the clinical expression include the pH profile of the residual enzyme activity and an additional neuraminidase defect.

Adult↗
PubMed1992

Analysis of two chondroitin sulfate utilization mutants of Bacteroides thetaiotaomicron that differ in their abilities to compete with the wild type in the gastrointestinal tracts of germfree mice.

Previously, we isolated two mutants of Bacteroides thetaiotaomicron that were unable to grow on the mucopolysaccharide chondroitin sulfate (CS). One of these mutants (46-1) was outcompeted by the wild type in the intestinal tracts of germfree mice, whereas the other mutant (46-4) competed equally with the wild type. In the present article, we report a detailed characterization of these two mutants. Assays of enzymes in the CS utilization pathway revealed that 46-1 did not express one of these enzymes, chondro-6-sulfatase. The absence of chondro-6-sulfatase activity in extracts from 46-1 allowed us to detect a previously unknown activity of another enzyme in the CS breakdown pathway, beta-glucuronidase. In addition to hydrolyzing its normal substrate (an unsulfated disaccharide), beta-glucuronidase also hydrolyzed the 6-sulfated disaccharide subunit of CS. Two-dimensional gel analysis of polypeptides produced by 46-1 showed that several proteins other than the 6-sulfatase were either missing or expressed aberrantly. Thus, 46-1 could be a regulatory mutant. Mutant 46-4 was unable to grow on CS, hyaluronic acid, or disaccharides of CS. Thus, expression of the CS pathway enzymes could not be induced. Nonetheless, the growth pattern of 46-4 and some other findings indicate that the structural genes for these enzymes were still intact. The most likely target of mutant 46-4 is a regulatory locus that is required for expression of CS utilization genes. A surprising characteristic of 46-1 was its inability to grow on heparin, a mucopolysaccharide which is structurally similar to CS but is utilized by a different pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

X-linked dominant chondrodysplasia punctata with decreased dihydroxyacetone phosphate acyltransferase activity.

BACKGROUND: We examined an 18-month-old girl with typical clinical features of X-linked dominant chondrodysplasia punctata (CDPX2) with decreased activity of dihydroxyacetone phosphate acyltransferase (DHAP-AT), previously reported in CDPX2. On the other hand, steroid sulfatase, whose activity is deficient or decreased in X-linked ichthyosis and X-linked recessive chondrodysplasia punctata, has been reported to be normal in CDPX2, although all of these diseases have ichthyotic skin changes. OBJECTIVE: We measured the activity of DHAP-AT and steroid sulfatase of the patients fibroblasts to confirm the DHAP-AT abnormality in CDPX2. RESULTS: The DHAP-AT activity was remarkably reduced, but steroid sulfatase activity was within normal levels when compared with those of 2 healthy controls. CONCLUSION: The abnormal metabolism in plasmalogen synthesis in CDPX2 was confirmed. It is, however, unknown how the decreased DHAP-AT activity is related to the skin changes.

Acyltransferases↗
PubMed1995

Genetic determinants of dopaminergic activity: potential role in blood pressure regulation.

Dopamine (DA) availability for precursor function and peripheral biological action is dependent on synthesis and inactivation enzymes, most of them have been cloned and located. An aromatic acid decarboxylase (AADC) defect has been reported in male homozygotic twins. The syndrome of complete dopamine-beta-hydroxylase deficiency with orthostatic hypotension and very high DA contributes to our understanding of the role of DA as a catecholamine with a peripheral biological action of its own. X-linked isolated monoamine oxidase A gene deficiency represents a marked disturbance of monoamine metabolism. The genes of the two major extraneuronal DA-metabolizing enzymes--catechol-O-methyl-transferase and phenolsulfotransferase (PST)-have also been defined. Of particular interest is a bidirectional shuttle system between the PST and sulfatase which have been cloned and located. DA, highly sulfoconjugated via PST, yields DA sulfate which is reconvertible by sulfatase to Free DA. A defect of sulfatase catalyzing this process results in a predominance of DA as biologically inactive DA sulfate and so attenuates the DA action. Enzymatic defects of DA synthesis and metabolism are thus genetic modulators of DA action.

Animals↗