Biocatalysts: The Different Classes and Applications for Synthesis of APIs
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
The enzyme classification adopted by the Enzyme Commission of the IUB is based on a hierarchically ordered sequence of numbers EC w.x.y.z: The first number denotes the general class (e.g., transferase, “2”). The second and the third number refer to the mechanism of the catalyzed reaction but allow to distinguish between different activities (e.g., transferring C1-groups, “2.1” together with methyltransferase, “2.1.1”). The forth number is a serial one within the sub-subclass. It is in the nature of such classification that it makes no distinction between enzymes catalyzing the same type of reaction but being of different sources, so that they may differ from each other with respect to chemical or physical properties due to which they can be separated from each other by physical methods. A similar situation exists in case of isoforms of enzymes that underwent different post-translational modifications. Enzymes belonging to the first enzyme class are oxidoreductases (EC 1.-.-.-) catalyzing oxidation-reduction reactions. If the catalyzed reaction is the oxidation of an alcohol (EC 1.1.-.-), the enzyme acts on the −CHR-OH group of the donor, being oxidized by donating hydrogen or an electron to the acceptor, e.g., NAD+ (EC 1.1.1.-). The fourth digit is a running number; the resulting systematic name is alcohol: NAD oxidoreductase with the EC classification 1.1.1.1 and the common name alcohol dehydrogenase. All enzymes have a systematic and a common name and are subdivided into six general classes as compiled in Table 7.1.
Macronutrients
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
The name of an enzyme has two parts. The first part is the name of the substrate, and the second part is terminated with a suffix -ase (54). For example, protease is an enzyme of the substrate protein. For the international nomenclature, the name of an enzyme is preceded by the two letters EC (Enzyme Commission) followed by four numbers. For example, E.C.2.7.1.1. The first number denotes one of the six main classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. The second number denotes the subclass and the third number denotes the sub-subclass. The last number denotes the serial number of the enzyme in its sub-subclass (53–54). Enzymes are classified based on the reactions they catalyze into six classes cited above. Oxidoreductases such as glutathione reductase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase are the enzymes that catalyze oxidation-reduction reactions of their substrates. Transferases transfer a functional group between two substrates such as a methyl or phosphate group. Hydrolases catalyze the hydrolysis reactions of carbohydrates, proteins, and esters. Lyases cleave various chemical bonds by other means than hydrolysis and oxidation for the formation of double bonds. Isomerases are involved in isomerization of substrate where interconversion of cis-trans isomers is implicated. Ligases such as alanyl-t-RNA synthetase, glutamine synthetase, and DNA ligases join together two substrates with associated hydrolysis of a nucleoside triphosphate (53–54).
Marine Algal Secondary Metabolites Are a Potential Pharmaceutical Resource for Human Society Developments
Se-Kwon Kim in Marine Biochemistry, 2023
Marine fungus like Caldariomyces fumago synthesizes chloroperoxidase is distinctive among peroxidases in that it has a cysteinic thiolate as a fifth axial ligand of the heme rather than an imidazole ligand. This enzyme is extremely versatile: it catalyzes not only peroxidase reactions, but also catalase and monooxygenase reactions, and it’s almost unusual, in that in the presence of H2O2 and halide ions, it can catalyze halogenation reactions. A few oxidoreductases are now available for use in the textile, food, and other fields, and many are being actively developed for future commercialization. Industrial-technical, specialty chemical synthesis, environmental, food, pharmaceutical, and personal healthcare are some of the industries where oxidoreductase is used. Oxidoreductase-based biocatalysts fit well with the creation of highly effective, economic, and ecologically friendly industries because they are specialized, energy-saving, and biodegradable.
A metabolic pathway for the prodrug nabumetone to the pharmacologically active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA) by non-cytochrome P450 enzymes
Published in Xenobiotica, 2020
Kaori Matsumoto, Tetsuya Hasegawa, Kosuke Ohara, Chihiro Takei, Tomoyo Kamei, Junichi Koyanagi, Tamiko Takahashi, Masayuki Akimoto
Several drugs containing alkyl side chains are metabolized to the corresponding ω-carboxylic acids by ADH and ALDH following initial ω-hydroxylation by CYP enzymes or others. Incubations with S9 fractions inferred that 6-MNE-ol was a substrate for NAD+-dependent enzymes. Many cytosolic oxidoreductases are capable of oxidizing the primary alcohol to the corresponding aldehyde using NAD+ as a cofactor, which is then converted to its reduced form, NADH. The present results indicated that the oxidized form of the cofactor NAD+ was required for the metabolism of nabumetone to 6-MNA in this process (Figure 6). As a general inhibitor of alcohol dehydrogenases, 4-MP, which is a NAD+-requiring enzyme, markedly inhibited the formation of 6-MNA (Figure 7). These results were consistent with the cofactor-dependent formation of 6-MNA. The sole end-product, 6-MNA, was definitely formed from 6-MNA-ol.
Integrated analysis of mRNA–m6A–protein profiles reveals novel insights into the mechanisms for cadmium-induced urothelial transformation
Published in Biomarkers, 2021
Bin Wu, Xu Jiang, Yapeng Huang, Xiaoling Ying, Haiqing Zhang, Bixia Liu, Zhuo Li, Dengfeng Qi, Weidong Ji, Xingming Cai
RNA-Seq and proteome datasets shared 518 DEGs in common (Figure 4(A)). GO and KEGGE enrichment analyses of the DEGs showed that with respect to biological processes, they were enriched in protein localization to organelles such as membrane and endoplasmic reticulum, RNA and carbohydrate catabolic process, nucleocytoplasmic transport, and transition of mitotic cell cycle. For cellular components, these DEGs were enriched in the ribosomal subunit and membranes. With respect to molecular function, they were enriched in molecule binding and oxidoreductase and isomerase activities (Figure 4(A)). KEGG enrichment analysis revealed that the shared DEGs were significantly enriched in oxidative phosphorylation, the pentose phosphate pathway, and arginine biosynthesis. Among these, the pentose phosphate pathway plays a key role in the energy metabolism of tumour cells (Figure 4(B)).
Integrated Analysis of Long Non-Coding RNA -mRNA Profile and Validation in Diabetic Cataract
Published in Current Eye Research, 2022
Xiaoyan Han, Lei Cai, Yumeng Shi, Zhixiang Hua, Yi Lu, Dan Li, Jin Yang
Using microarray and bioinformatic analysis, we found a total of 8326 lncRNAs and 3303 mRNAs were differently expressed in DC lens samples compared to the controls, and the intergenic lncRNAs possessed the largest proportion. Based on the results of GO analysis, we found that the upregulated mRNAs were mainly distributed in intracellular part and they were mostly involved in oxidative process and metabolic process. The molecular function was highly enriched in protein binding, oxidoreductase activity and RNA binding. As to downregulated mRNAs, they were primarily distributed in membrane part and participated in the protein lipidation process, and the molecular function were mainly involved in transmembrane transporter activity. Generally, these results showed that differentially expressed mRNA was mainly related to oxidative stress, protein modification and RNA binding. In the KEGG pathway analysis, the upregulated mRNAs were mostly associated with glucose metabolic pathway, including the glycolysis/gluconehenesis, carbon metabolism. In addition, the AGE-RAGE signaling pathway and lysosome were also included. For the downregulated mRNAs, they mainly involved in molecule bisosynthesis process. Briefly, the results of KEGG presented the dysregulated mRNAs were mainly involved the glucose metabolism and the lysosome pathway.
Related Knowledge Centers
- Biochemistry
- Cofactor
- Electron Transport Chain
- Enzyme
- Nicotinamide Adenine Dinucleotide
- Nicotinamide Adenine Dinucleotide Phosphate
- Oxidizing Agent
- Photosystem
- Reducing Agent
- Mitochondrion