Introduction to Enzymes
John C. Matthews in Fundamentals of Receptor, Enzyme, and Transport Kinetics, 2017
Now suppose that we mix some l-glucose, d-galactose, and some d-ribose with the d-glucose and run the same reaction. Again all we want is 3-acetyl-d-glucose as our product. What we will get is a mixture of all possible acetylation products of all four sugars. Now instead, let us mix acetic acid, d-glucose, l-glucose, d-ribose, and d-galactose at pH 7 and add the imaginary enzyme d-glucose-3-acetylase. After allowing time for the reaction to come to completion we will find 3-acetyl-d-glucose, l-glucose, d-ribose and d-galactose in the mixture, along with some unreacted acetic acid. The enzyme has provided for both reactant (called the substrate in enzyme terminology) and product specificity. Another thing that the enzyme accomplished was that it allowed the reaction to proceed at neutral pH as compared with low pH for the nonenzymatic reaction.
Xenobiotic Biotransformation
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
Aldehyde dehydrogenases (EC 1.2.1.3.) catalyze the oxidation of aldehydes to acids by using NAD as co-factor. The physiological substrates for the enzymes are unknown; the substrate specificity is broad. Classical substrates include acetaldehyde, formaldehyde, and glycolaldehyde, which are the biotransformation products of ethanol, methanol, and ethylene glycol, respectively. The enzymes are present in all organs and in cytosol, mitochondria and microsomes. Liver has the highest activity, but kidney also possesses high activity. The enzymes exist as several isozymes within the cytosolic, mitochrondrial, and microsomal compartments. One cytosolic isozyme is specific for the oxidation of formaldehyde complexed with glutathione and is referred to as formaldehyde dehydrogenase. Additional isozymes within the cytosol are differentiated by selective induction with PB or TCDD and 3-MC. The isozyme induced by TCDD and 3-MC has received special study due to its increased activity in tumor cells [see Marselos and Lindahl (1988)]. Since acetaldehyde is preferentially oxidized in mitochondria, an isozyme for its oxidation may be localized in these structures. Additional mitochrondrial isozymes can be differentiated by selective inhibition with the prototype aldehyde dehydrogenase inhibitor, disulfiram.
Macronutrients
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
Enzymes are globular proteins which are able to catalyze biochemical reactions. Enzymes accelerate the conversion of substrates into useful products in a buried pocket within the active site of the enzyme (53). In cells and organisms, most reactions are catalyzed by enzymes, which are regenerated during the course of a reaction, although not all reactions in nature require catalysis (53–55). These biological catalysts are physiologically important because they speed up the rates of reactions that would otherwise be too slow to support life (54). Enzymes accelerate the rates of such reactions by well over a million-fold, so reactions that would take years in the absence of catalysis can occur in fractions of seconds if catalyzed by the appropriate enzyme (55). Each enzyme has a specific active site where only one substrate or certain kind of substrate can bind to it for the conversion of the substrate into useful products. This phenomenon may be refered to as ‘the lock and key model’. For example, starch is the only substrate of the enzyme amylase which converts starch into soluble glucose, an essential macronutrient and energizing product. Each cell contains thousands of different enzymes that facilitate specific cellular reactions (3, 55). Like proteins, enzymes contain chains of amino acids linked together. The characteristic of each enzyme is determined by the different sequence of amino acid arrangement. When the bonds between the amino acid are weak, they may be broken by high temperatures or high levels of acids, and become inactive.
Serine protease inhibitors to treat inflammation: a patent review (2011-2016)
Published in Expert Opinion on Therapeutic Patents, 2018
Feryel Soualmia, Chahrazade El Amri
Reversible inhibitors include two types of inhibitors forming non-covalent complexes with the targeted enzymes. Substrate analogs, which are molecular entities that reproduce the main structural characteristics of the substrate but are not transformed by the enzyme, are counted. The other group is represented by transition state analogs, differentiated from substrate analogs by their structural similarities to the ground state with one of the transition states encountered during the catalytic process. Thus, the affinity of these inhibitors to the enzyme is much higher than that observed for the substrates. These inhibitors are therefore commonly referred to as ‘high-affinity inhibitors’ or ‘tight-binding inhibitors.’ Irreversible inhibitors are subdivided into five groups and are characterized by the formation of covalent bonds between the enzyme and the inhibitor, which can lead to the formation of a definitive or transient covalent complex. In the latter case, the enzyme is reactivated more or less slowly.
Structure-activity relationship of atorvastatin derivatives for metabolic activation by hydrolases
Published in Xenobiotica, 2020
Kenta Mizoi, Masato Takahashi, Sachiko Sakai, Takuo Ogihara, Masami Haba, Masakiyo Hosokawa
The substrate specificity of these enzymes has been well investigated. However, relatively little work has been done on the structure-activity relationship for the activation of prodrugs by these hydrolases, even though the prediction of metabolic activation in vivo is an important aspect of prodrug design. We previously established a synthesis of atorvastatin esters as prodrug models (Mizoi et al., 2016). We found that atorvastatin derivatives show greater metabolic activation in the presence of human liver microsomes (HLM) than human small-intestinal microsomes (HIM), suggesting that they were hydrolyzed by hCES1. In the current report, we describe a comprehensive study of the structure-activity relationship for metabolic activation of 31 kinds of synthesized atorvastatin esters, thioesters, amides, and lactone by microsomes and hydrolases in order to identify candidate prodrugs and obtain basic data for prodrug design.
Neutrophil extracellular traps induce tumor metastasis through dual effects on cancer and endothelial cells
Published in OncoImmunology, 2022
Ze-Zhou Jiang, Zhi-Peng Peng, Xing-Chen Liu, Hao-Fan Guo, Meng-Meng Zhou, Da Jiang, Wan-Ru Ning, Yu-Fan Huang, Limin Zheng, Yan Wu
Hexokinase Colorimetric Assay Kit (HK-1-Y, Comin Biotechnology, Suzhou, China), Phosphofructokinase Activity Colorimetric Assay Kit (PFK-1-Y, Comin Biotechnology, Suzhou, China), Pyruvate Kinase Activity Assay Kit (PK-1-Y, Comin Biotechnology, Suzhou, China), Lactate Dehydrogenase Activity Assay Kit (LDH-1-Y, Comin Biotechnology, Suzhou, China), Glucose-6-phosphate Dehydrogenase Activity Assay Kit (G6PDH-1-Y, Comin Biotechnology, Suzhou, China) and NADPH oxidase Activity Assay Kit (NOX-1-Y, Comin Biotechnology, Suzhou, China) were used to measure the enzyme activity of neutrophil cells. In brief, cells were collected and washed once with PBS before being exposed to lysis buffer. The direct substrate, downstream enzymes, and substrates of downstream enzymes for the respective measured enzyme were added according to the manufacturers’ descriptions. The ultimate products for each measured enzyme were NADPH or NADH, the absorbance of which could be detected at 340 nm by a spectrophotometer.
Related Knowledge Centers
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