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).
Honey-Based Polyphenols: Extraction, Quantification, Bioavailability, and Biological Activities
Megh R. Goyal, Arijit Nath, Rasul Hafiz Ansar Suleria in Plant-Based Functional Foods and Phytochemicals, 2021
Although there are resins (like Oasis HLB) that are more efficient for polar compounds (gallic acid can be retained), yet their performance is generally lower for less polar substances (like quercetin or kaempferol). Istasse et al. [46] confirmed the formation of cis isomers from the trans polyphenol standards. The cis isomers were identified by comparing their spectra with the spectra of the standard solutions in HPLC-DAD and LC-UV-MS. The authors concluded that cis isomers can be formed even in the absence of light, even though the light was previously considered to be essential for this transformation. They confirmed that the causes are not yet clear, as isomerization can be induced by simple exposure to ambient temperature in methanolic solution or an unknown reaction with the adsorbent [43].
Application of Bioresponsive Polymers in Drug Delivery
Deepa H. Patel in Bioresponsive Polymers, 2020
Stimuli-responsive nanocarriers (SRNs) are unique nanosized delivery vectors which are endowed with “load and release” modalities in their constituent units. Any specific intracellular, extracellular physical, chemical, or biochemical stimulus will alter the structural properties of the nanocarriers and leading to change in drug release pattern. The dynamic changes observed are generally due to decomposition, isomerization, polymerization, supramolecular assembly, etc. The specificity w.r.t. pH, enzyme, protein over-expression, ionic changes allowed the nanocarriers to release their payload with spatio-temporal specificity. The precise drug release would minimize the adverse reaction and side effects. These carriers are actually simulating the feedback mechanism operating in nature where the presence, absence, or excess of any physical, chemical, or physico-chemical factors regulates a series of biochemical processes.
Restoring the biological activity of crizanlizumab at physiological conditions through a pH-dependent aspartic acid isomerization reaction
Published in mAbs, 2023
Fabian Bickel, François Griaud, Wolfram Kern, Frieder Kroener, Manuela Gritsch, Jérôme Dayer, Samuel Barteau, Blandine Denefeld, Chi-Ya Kao-Scharf, Manuel Lang, Izabela Slupska-Muanza, Carla Schmidt, Matthias Berg, Jürgen Sigg, Lina Boado, Dirk Chelius
The chemical isomerization reaction is favored in the presence of glycine at the C-terminus of the isomerization site, namely at a DG motif, and has been studied in detail using model peptides.4–9 Additional influencing factors of the isomerization reaction are the protein structure itself,10 as well as environmental conditions. During aspartic acid isomerization, the rate-limiting10 accumulation of succinimide is favored at mildly acidic conditions8 and under elevated temperatures.11 The following succinimide hydrolysis to iso-aspartic acid and aspartic acid is preferred at neutral and basic pH with a ratio of approximately 3:1.4,12–15 MAbs are often stored under mildly acidic or neutral conditions to ensure their stability,16 which promotes the formation of succinimide and its subsequent hydrolysis in this class of biopharmaceuticals.
Identification and characterization of an unexpected isomerization motif in CDRH2 that affects antibody activity
Published in mAbs, 2023
Meiqi Yi, Jian Sun, Hanzi Sun, Yifei Wang, Shan Hou, Beibei Jiang, Yuanyuan Xie, Ruyue Ji, Liu Xue, Xiao Ding, Xiaomin Song, April Xu, Chichi Huang, Quan Quan, Jing Song
Therapeutic mAbs degrade via multiple pathways during expression, purification, formulation, storage, and delivery. Post-translational modifications (PTMs) or chemical modifications of CDR amino acid residues may have negative effects on antigen binding, leading to a decrease in potency, and therefore characterization of chemical modifications is an important part of evaluating the stability of therapeutic mAbs.5,6 Asp isomerization is one of the major chemical modifications of proteins under typical processing formulation and storage conditions.7 In mildly acidic buffers, aspartic acid (Asp) residues can form a cyclic imide intermediate, succinimide (Asu), via nucleophilic attack of the carbonyl group on the Asp side chain by the amide nitrogen on the backbone.8,9 The Asu loop is unstable under alkaline pH conditions and can be rapidly hydrolyzed into Asp and isoaspartic acid (isoAsp) residues (Figure 1). Previous studies have reported a 1:3 ratio of Asp to isoAsp from the succinate intermediate. The rate of isomerization reaction depends on various factors, including pH, temperature, primary structure, higher order structure, ionic strength, and other buffer conditions. Generally, antibody isomerization is more readily observed after incubation at elevated temperature and low pH.10–12 The formation of isoAsp may lead to an immune response and the loss of biological activity.13,14
In silico prediction of post-translational modifications in therapeutic antibodies
Published in mAbs, 2022
Shabdita Vatsa
Asp isomerization is sensitive to temperature and the dielectric constant of the solvent. At neutral pH, a high dielectric constant for solvents increases the pKa of Asp, which increases the concentration of the carboxylic acid (COOH) form of the Asp side chain. The COOH form is more reactive and prone to isomerization than the carboxylate form (COO−).39 High temperatures can also accelerate the rate of isomerization reactions. Moreover, flanking residues, ionization state, and higher-order structure also influences isomerization.40 For example, the risk of isomerization is highest for Asp residues within random coils due to structural flexibility and higher solvent exposure.41 The risk of isomerization also differs for different CDR loops. Asp isomerization at liable motifs is more likely with the CDR H3, H2, and L1 loops.42
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