Lysosomal Enzymes
Acid Vesicles

Author: Gianpiero Pescarmona
Date: 13/03/2009


SUMF1 SUMF2 activate Sulfatases (GALNS, ARSA, STS and ARSE)

Ballabio A

Sulfatase regulate lysosome acidification

Many proteins involved in lysosome function have a substantial % of Tryptophan

  • SUMF1 (ca 2,8) SUMF2 (ca 4 %)
  • Sulfatases ( ca 2,5)
  • Cathepsin (range from 0,8 to 3.5)
  • xyz


Endocrinology. 2002 Mar;143(3):814-9.
Characterization of iodothyronine sulfatase activities in human and rat liver and placenta.

Kester MH, Kaptein E, Van Dijk CH, Roest TJ, Tibboel D, Coughtrie MW, Visser TJ.

Department of Internal Medicine, Erasmus University Medical School, 3000 DR Rotterdam, The Netherlands.

In conditions associated with high serum iodothyronine sulfate concentrations, e.g. during fetal development, desulfation of these conjugates may be important in the regulation of thyroid hormone homeostasis. However, little is known about which sulfatases are involved in this process. Therefore, we investigated the hydrolysis of iodothyronine sulfates by homogenates of V79 cells expressing the human arylsulfatases

  • A (ARSA),
  • B (ARSB)
  • C (ARSC;steroid sulfatase)

as well as tissue fractions of human and rat liver and placenta. We found that only the microsomal fraction from liver and placenta hydrolyzed iodothyronine sulfates. Among the recombinant enzymes only the endoplasmic reticulum-associated ARSC showed activity toward iodothyronine sulfates; the soluble lysosomal ARSA and ARSB were inactive. Recombinant ARSC as well as human placenta microsomes hydrolyzed iodothyronine sulfates with a substrate preference for 3,3'-diiodothyronine sulfate (3,3'-T(2)S) approximately T(3) sulfate (T(3)S) >> rT(3)S approximately T(4)S, whereas human and rat liver microsomes showed a preference for 3,3'-T(2)S > T(3)S >> rT(3)S approximately T(4)S. ARSC and the tissue microsomal sulfatases were all characterized by high apparent K(m) values (>50 microM) for 3,3'-T(2)S and T(3)S. Iodothyronine sulfatase activity determined using 3,3'-T(2)S as a substrate was much higher in human liver microsomes than in human placenta microsomes, although ARSC is expressed at higher levels in human placenta than in human liver. The ratio of estrone sulfate to T(2)S hydrolysis in human liver microsomes (0.2) differed largely from that in ARSC homogenate (80) and human placenta microsomes (150). These results suggest that ARSC accounts for the relatively low iodothyronine sulfatase activity of human placenta, and that additional arylsulfatase(s) contributes to the high iodothyronine sulfatase activity in human liver. Further research is needed to identify these iodothyronine sulfatases, and to study the physiological importance of the reversible sulfation of iodothyronines in thyroid hormone metabolism.

Clin Exp Metastasis. 2009;26(6):535-45. Epub 2009 Mar 22.
Arylsulfatase B regulates colonic epithelial cell migration by effects on MMP9 expression and RhoA activation.

Bhattacharyya S, Tobacman JK.

Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

Arylsulfatase B (ASB; N-acetylgalactosamine-4-sulfatase; 4-sulfatase; ARSB) is the enzyme that removes 4-sulfate groups from N-acetylgalactosamine 4-sulfate, which combines with glucuronate to form the disaccharide unit of chondroitin-4-sulfate (C4S). In this study, we report how variation in expression of ASB affected the migration of human colonic epithelial cells. In the T84 cell line, derived from lung metastasis of malignant colonic epithelial cells, the activity of ASB, as well as steroid sulfatase, arylsulfatase A, and galactose-6-sulfatase, were significantly less than in normal, primary colonic epithelial cells and in the NCM460 cell line which was derived from normal colonocytes. In the T84 cells, matrix metalloproteinase 9 (MMP9), activated RhoA, and cell migration, as well as C4S content, were significantly more than in the NCM460 cells. Silencing and overexpression of ASB had inverse effects on MMP9, activated RhoA, and cell migration, as well as the C4S content, in the NCM460 and T84 cells.

When ASB expression was silenced by siRNA in the NCM460 cells,

  • MMP9 secretion increased to over 3 times the basal level,
  • activated RhoA increased 85%,
  • cell migration increased 52%.

Following overexpression of ASB

  • MMP9 declined 51%,
  • activated RhoA declined 51%,
  • cell migration decreased 37%.

These findings demonstrate marked effects of ASB expression on the migratory activity of colonic epithelial cells, activated RhoA, and MMP9, and suggest a potential vital role of ASB, due to its impact on chondroitin sulfation, on determination of the invasive phenotype of colonic epithelial cells.

RhoA activation depends on HMGCoA reductase activity? ASB inhibits cholesterol synthesis?

Eur J Pediatr. 1988 Aug;147(6):634-8.
Multiple sulfatase deficiency with a novel biochemical presentation.

Constantopoulos G.

Developmental and Metabolic Neurology Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20892.

Deficient activities of cerebroside-sulfatase, N-Acetylgalactosamine-4-sulfatase and iduronide 2-sulfatase in the lymphocytes of a patient suspected of metachromatic leukodystrophy, established the diagnosis of multiple sulfatase deficiency (MSD). Cultured skin fibroblasts (of early passage) from the patient had normal levels of activity for the three sulfatases. One week after the first examination, the activities of the three sulfatases in the fibroblasts of the patient declined and within a month were 4%-29% of normal. Total urinary glycosaminoglycans were within normal range. However, further examination showed an increase in the concentration of heparan sulfate, which comprised more than 50% of the total, compared with less than 20% in normal controls. Urinary sulfatides, cholesterol esters, cholesterol, and triglycerides were increased. The results from the study of this unique case of MSD suggest that time-dependent changes affect the activities of sulfatases in MSD. These results also demonstrate the necessity of assaying the sulfatases in both lymphocytes and fibroblasts from suspected cases of MSD.

Lysosomal pH and ARSB activity

Chloroquine reduces arylsulphatase B activity and increases chondroitin-4-sulphate: implications for mechanisms of action and resistance. 2009

The study data demonstrated: 1) decline in ASB activity following chloroquine exposure; 2) inverse correlation between ASB activity and C4S content; 3) increased content of chondroitin-4-sulphate disaccharides following chloroquine exposure;

Monensin stimulation of arylsulfatase B activity in human chondrocytes. 1986

Secreted and intracellular arylsulfatase B (ASB) activities were measured in normal and osteoarthritic (OA) human chondrocyte cultures in the absence and presence of monensin, ammonium chloride, and chloroquine. Of the three agents added, only monensin produced a significant stimulation of secreted enzyme activity. Osteoarthritic cells consistently exhibited a three-fold higher level of secreted specific ASB activity than did normal cells, with or without monensin. When compared with normal cells, OA cells also consistently exhibited a twofold heightened intracellular specific enzyme activity both in the absence or presence of monensin.

ARSB expression

Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice. 2009

Skin homogenates from mice treated with anti-IL5 had decreased mRNA expression of arylsulfatase B (Arsb), diamine oxidase (amiloride-binding protein 1, also called histaminase; Abp1) and Il10, which are mediators that eosinophils may release to quench inflammation


Papers arylsulfatase B cftr B+cftr

Evaluating candidate agents of selective pressure for cystic fibrosis. 2007

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