Biochemical characterization of chitotriosidase enzyme: comparison between normal individuals and patients with Gaucher and with Niemann–Pick diseases

Wajner, Alessandro; Michelin, Kristiane; Burin, Maira Graeff; Pires, Ricardo Flores; Pereira, Maria Luiza Saraiva; Giugliani, Roberto; Coelho, Janice Carneiro

doi:10.1016/j.clinbiochem.2004.06.008

Cited by 52 publications

(44 citation statements)

References 17 publications

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“…Our results showed that the ChT activity was higher in most GD type 1 patients analyzed than in the healthy controls, which is in accordance with previous studies (Hollak et al 1994;Ries et al 2006;Wajner et al 2004Wajner et al , 2007. colleagues (2004, 2007) reported that the ChT activity was around 600-fold greater in untreated GD patients of Brazilian origin than in healthy individuals.…”

Section: Discussionsupporting

confidence: 93%

Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

et al. 2012

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Section: Discussionsupporting

confidence: 93%

Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

et al. 2012

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“…Gaucher's disease (13), sarcoidosis (14,15), cardiovascular risk (16), coronary artery disease 79 (17), primary prostate cancer and benign prostatic hyperplasia (18), nonalcoholic 80 steatohepatitis (19), and Niemann-Pick disease (20). The only currently known physiological 81 implications of the elevated HCHT levels are a better defense against chitin-containing 82 pathogens (4) and the triggering of human macrophage activation by HCHT-mediated chitin 83 and chitosan degradation (21).…”

Section: Hcht Is Up-regulated In a Series Of Diseases And Medical Conmentioning

confidence: 99%

Human Chitotriosidase-Catalyzed Hydrolysis of Chitosan

et al. 2011

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 ABSTRACT: Chitotriosidase (HCHT) is one of two family 18 chitinases produced by 45 humans, the other being acidic mammalian chitinase (AMCase). The enzyme is thought to be 46 part of the human defense mechanism against fungal parasites, but its precise role and the 47 details of its enzymatic properties have not yet been fully unraveled. We have studied 48properties of HCHT by analyzing how the enzyme acts on high molecular-weight chitosans, 49 soluble co-polymers of β-1,4-linked N-acetylglucosamine (GlcNAc, A) and glucosamine 50 (GlcN, D). Using methods for in-depth studies of the chitinolytic machinery of bacterial 51 family 18 enzymes, we show that HCHT degrades chitosan primarily via an endo-processive 52 mechanism, as would be expected on the structural features of its substrate-binding cleft. The 53 preferences of HCHT subsites for acetylated versus non-acetylated sugars were assessed by 54 sequence analysis of obtained oligomeric products showing a very strong, absolute, and a 55 relative weak preference for an acetylated unit in the -2, -1, +1 subsite, respectively. The 56 latter information is important for the design of inhibitors that are specific for the human 57 chitinases and also provide insight into what kind of products may be formed in vivo upon 58 administration of chitosan-containing medicines or food products. 59 KEYWORDS: Human chitinase; chitosan; chitin; processivity; chitotriosidase. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 4 Chitin, an insoluble linear polysaccharide consisting of repeated units of β-1,4-N-66 linked acetylglucosamine [(GlcNAc) n ], is common as a structural polymer in crustaceans, 67 arthropods, fungi, and parasitic nematodes. The metabolism of chitin in nature is controlled 68 by enzymatic systems that produce and break down chitin, primarily chitin synthases and 69 chitinases, respectively. Chitinases are thought to play important roles in anti-parasite 70 responses in several life forms, including humans (1-4). Even though chitin and chitin 71 synthases have not been found in humans, we produce two active chitinases that are 72 categorized as family 18 chitinases based on sequence-based classification of glycoside 73 hydrolases (5). These two enzymes are called acidic mammalian chitinase (AMCase) (6) and 74 human chitotriosidase (HCHT) (7) and both are believed to play roles in anti-parasite 75 responses (8, 9). While AMCase is found in the stomach (6), in tears (10), sinus mucosa (11), 76 and lungs (12), HCHT is primarily expressed in activated human macrophages (13). 77HCHT is up-regulated in a series of diseases and medical conditions such as 78Ga...

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“…Human chitotriosidase is a member of the chitinase protein family and is involved in the defense against pathogens containing chitin, such as fungi, nematodes and insects [1]. Research into Gaucher disease led to the discovery of this endogenous chitinase in humans [2], which is selectively expressed in chronically activated tissue macrophages [1] and regarded as a biochemical marker of macrophage activation [3, 4].…”

Section: Introductionmentioning

confidence: 99%

“…Research into Gaucher disease led to the discovery of this endogenous chitinase in humans [2], which is selectively expressed in chronically activated tissue macrophages [1] and regarded as a biochemical marker of macrophage activation [3, 4]. Assay of chitotriosidase activity is used to monitor Gaucher disease patients on enzyme replacement therapy [2, 4].…”

Section: Introductionmentioning

confidence: 99%

Chitotriosidase Activity in the Serum of Patients with Sarcoidosis and Pulmonary Tuberculosis

Bargagli

Margollicci²,

Nikiforakis³

et al. 2007

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Background: Human chitotriosidase is a chitinase selectively expressed by activated macrophages. An increase in chitotriosidase activity was previously described by us in the serum and bronchoalveolar lavage of sarcoidosis patients. Objective: The aim of the present study was to analyze serum chitotriosidase activity in a larger number of sarcoidosis patients to verify the reported increase with respect to controls and to compare serum chitotriosidase levels in patients with sarcoidosis and tuberculosis, two granulomatous disorders of different etiology. Methods: Chitotriosidase activity was measured in the serum of 96 sarcoidosis patients, 15 pulmonary tuberculosis patients and 30 healthy controls. Results: We found significantly higher serum chitotriosidase activity in sarcoidosis patients than controls (p < 0.01) and in sarcoidosis patients than tuberculosis patients (p < 0.01), confirming a striking elevation of chitotriosidase activity (>10 times greater than normal) in pulmonary sarcoidosis patients. This is the first time that chitotriosidase activity has been analyzed in the serum of patients with pulmonary tuberculosis; it was found to be significantly lower than in sarcoidosis patients and not significantly greater than in controls. Conclusion: Although the mechanisms leading to the increase in chitotriosidase activity in sarcoidosis are still unknown, this enzyme may be specifically involved in the pathogenesis of the disease. Further studies with a greater number of patients are needed to confirm these results and to determine whether chitotriosidase could be a marker with diagnostic or prognostic value in sarcoidosis.

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Biochemical characterization of chitotriosidase enzyme: comparison between normal individuals and patients with Gaucher and with Niemann–Pick diseases

Cited by 52 publications

References 17 publications

Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

Human Chitotriosidase-Catalyzed Hydrolysis of Chitosan

Chitotriosidase Activity in the Serum of Patients with Sarcoidosis and Pulmonary Tuberculosis

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