Carboxylic Ester Hydrolases

Publication Title: 
Biotechnology and Applied Biochemistry

Statistically based experimental designs were applied to the optimization of cultural conditions for tannase production, an enzyme of great importance, from Penicillium variable. First, D-optimal design was used to evaluate the effects of variables, including concentrations of substrate (chebulic myrobalan, fruits of the tree Terminalia chebula ), pH, inoculum density, agitation and incubation period, on tannase production. The optimum value of pH and inoculum density thus obtained was 5.0 and 5 x 10(7) spores/50 ml respectively.

Author(s): 
Saxena, Shashi
Saxena, Rajendra K.
Publication Title: 
Journal of Basic Microbiology

Modified solid-state fermentation (MSSF) of tannin-rich substrates for production of tannase and gallic acid was carried out using two fungal cultures, Rhizopus oryzae (RO IIT RB-13, NRRL 21498) and Aspergillus foetidus (GMRB013 MTCC 3557). The tannin rich substrates included powdered fruits of Terminalia chebula and Caesalpinia digyna pod cover powder. The different environmental parameters for the maximum production of tannase and gallic acid were optimized through media engineering.

Author(s): 
Mukherjee, Gargi
Banerjee, Rintu
Publication Title: 
Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan

Senescence Marker Protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases with aging. Recently, we identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonases (GNL) of animal species. GNL was a key enzyme which involved in vitamin C biosynthesis, and the essential role of SMP30 in this synthetic process was verified by a nutritional study. SMP30 knockout mice developed symptoms of scurvy when fed a vitamin C-deficient diet, verifying the pivotal role of SMP30 in vitamin C biosynthesis.

Author(s): 
Ishigami, Akihito
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Aspirin (acetylsalicylic acid) and clopidogrel are two major antithrombogenic agents that are widely used for the treatment and prevention of cerebro- and cardiovascular conditions such as stroke. Combined use produces enhanced therapeutic effect. Aspirin and clopidogrel both are esters, and hydrolysis leads to decreased or inactivated therapeutic activity. The aim of the study was to determine whether aspirin and clopidogrel are hydrolyzed by the same enzyme(s), thus reciprocally prolonging the antithrombogenic activity.

Author(s): 
Tang, Man
Mukundan, Madhu
Yang, Jian
Charpentier, Nathan
LeCluyse, Edward L.
Black, Chris
Yang, Dongfang
Shi, Deshi
Yan, Bingfang
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Oseltamivir is the main medicine recommended by the World Health Organization in anticipation of next influenza pandemic. This anti-influenza viral agent is an ester prodrug, and the antiviral activity is achieved by its hydrolytic metabolite: oseltamivir carboxylate. In this study, we report that the hydrolytic activation is catalyzed by carboxylesterase human carboxylesterase (HCE) 1. Liver microsomes rapidly hydrolyzed oseltamivir, but no hydrolysis was detected with intestinal microsomes or plasma.

Author(s): 
Shi, Deshi
Yang, Jian
Yang, Dongfang
LeCluyse, Edward L.
Black, Chris
You, Li
Akhlaghi, Fatemeh
Yan, Bingfang
Publication Title: 
Molecular Pharmacology

Carboxylesterases constitute a class of enzymes that play important roles in the hydrolytic metabolism of drugs and other xenobiotics. Patients with liver conditions such as cirrhosis show increased secretion of proinflammatory cytokines [e.g., interleukin-6 (IL-6)] and decreased capacity of hydrolysis. In this study, we provide a molecular explanation linking cytokine secretion directly to the decreased capacity of hydrolytic biotransformation.

Author(s): 
Yang, Jian
Shi, Deshi
Yang, Dongfang
Song, Xiulong
Yan, Bingfang
Publication Title: 
Diabetes, Obesity & Metabolism

AIM: To elucidate the mechanism by which rosiglitazone regulates adipose triglyceride lipase (ATGL). METHODS: Male C57Bl/6 mice were treated with rosiglitazone daily (10 mg/kg body weight), and adipose tissues were weighed and preserved for mRNA and protein analysis of ATGL. In parallel, preadipocyte (3T3-L1) cells were differentiated with insulin/dexamethasone/3-isobutyl-1-methlxanthine cocktail or rosiglitazone, and ATGL levels were measured with real-time PCR, western blotting and immunohistochemistry.

Author(s): 
Liu, L.-F.
Purushotham, A.
Wendel, A. A.
Koba, K.
DeIuliis, J.
Lee, K.
Belury, M. A.
Publication Title: 
Toxicology

Carboxylesterases play important roles in the metabolism of xenobiotics and detoxication of insecticides. Without exception, all mammalian species studied express multiple forms of carboxylesterases. Several rat carboxylesterases are well-characterized including hydrolase A, B and S, and the expression of these enzymes is significantly suppressed by glucocorticoid dexamethasone. In this study, we used multiple experimental systems and presented a molecular mechanism for the suppression. Rats receiving one or more daily injections of dexamethasone consistently expressed lower HA, HB and HS.

Author(s): 
Shi, Deshi
Yang, Jian
Yang, Dongfang
Yan, Bingfang
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Altered folate homeostasis is associated with many clinical and pathological manifestations in the CNS. Notably, folate-mediated one-carbon metabolism is essential for methyltransferase-dependent cellular methylation reactions. Biogenesis of protein phosphatase 2A (PP2A) holoenzyme containing the regulatory B(alpha) subunit, a major brain tau phosphatase, is controlled by methylation.

Author(s): 
Sontag, Jean-Marie
Nunbhakdi-Craig, Viyada
Montgomery, Lisa
Arning, Erland
Bottiglieri, Teodoro
Sontag, Estelle
Publication Title: 
Journal of Lipid Research

Z-Guggulsterone is a major ingredient in the Indian traditional hypolipidemic remedy guggul. A study in mice has established that its hypolipidemic effect involves the farnesoid X receptor (FXR), presumably by acting as an antagonist of this receptor. It is generally assumed that the antagonism leads to induction of cytochrome P450 7A1 (CYP7A1), the rate-limiting enzyme converting free cholesterol to bile acids. In this study, we tested whether Z-guggulsterone indeed induces human CYP7A1.

Author(s): 
Yang, Dongfang
Yang, Jian
Shi, Deshi
Xiao, Da
Chen, Yi-Tzai
Black, Chris
Deng, Ruitang
Yan, Bingfang
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