Biocatalytic Reduction of Organic Compounds by Marine-Derived Fungi
Se-Kwon Kim in Marine Biochemistry, 2023
The ERs most used in research is the OYE family of flavin oxidoreductases (EC 1.6.99.1). These enzymes can catalyze the asymmetric reduction of α,β-unsaturated alkenes in a ping-pong bi-bi mechanism. The hydride transfer from the nicotinamide moiety of NAD(P)H to the enzyme-bound flavin occurs in a reductive half-reaction. When oxidized to NAD(P)+, the transfer of the hydride ion from the reduced flavin to the alkene takes place in an oxidative half-reaction [13]. The alkene is bound to the active site of the enzyme by hydrogen- bonding via His/His or His/Asn amino acid interaction, which enhances the C=C bond polarization and supports the hydride transfer from FMNH2 to the C-β of the alkene [13]. Proton transfer occurs simultaneously from the Tyr amino acid residue of the opposite side and completes the reduction reaction in Figure 15.5.
Drug-Induced Abnormalities of Liver Heme Biosynthesis
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
2-Allyl-2-isopropylacetamide is not the only unsaturated drug capable of converting the heme of cytochrome P450 into green pigments. Several other drugs containing a side chain with a terminal double bond have been shown to be similarly effective (including allyl-barbiturates used therapeutically in humans, Levin et al., 1973) and, in addition, drugs containing an unsaturated acetylenic triple bond, among these the ethynyl-substituted steroids of the contraceptive pill (White and Muller-Eberhard, 1977; White, 1978, 1981). The simplest unsaturated compounds of both the alkene and alkyne series, ethylene and acetylene themselves (Figure 3b and c), were also active. A list of the unsaturated compounds capable of destroying cytochrome P450 and a more detailed coverage of the metabolism of these compounds and mechanisms of heme destruction can be found in Ortiz de Montellano and Correia (1983), White (1984), and De Matteis (1987), where additional references to the work summarized below are also given.
Renal Drug-Metabolizing Enzymes in Experimental Animals and Humans
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
Epoxide hydrolases are enzymes that catalyze the conversion of epoxides to dihydrodiols, thus preventing or reducing their reaction with cellular target macromolecules (protein and/or DNA). Three forms of epoxide hydrolase have been identified in the liver, one in the cytosol and two membrane-associated forms. The enzyme in the cytosol fraction catalyzes the hydration of several alkene oxides (e.g., trans-stilbene oxide, styrene oxide) and is inducible by clofibrate and nafenopin (Hammock and Ota, 1983; Waechter et al., 1988). Of the two known microsomal forms, one catalyzes the conversion of cholesterol-5,6-oxide to the corresponding diol and displays no activity towards xenobiotic epoxides (Oesch et al., 1984). The second and major microsomal form is responsible for the hydration of a wide variety of xenobiotic arene and alkene oxides (e.g., benzo(a)pyrene 4–5 oxide, styrene oxide) (Oesch et al., 1971). This enzyme is both immunologically and enzymatically distinct from the cholesterol-5, 6-epoxide hydrolase and the cytosolic form. The xenobiotic-metabolizing form of epoxide hydrolase is localized to the nuclear membrane (Gonzalez and Kasper, 1982) and is found in association with the cytochrome P-450 mixed-function oxidase system, which catalyzes the oxidation of both endogeneous and xenobiotic compounds to electrophilic epoxides (see the section titled Cytochromes P-450).
Linkers in fragment-based drug design: an overview of the literature
Published in Expert Opinion on Drug Discovery, 2023
Dylan Grenier, Solène Audebert, Jordane Preto, Jean-François Guichou, Isabelle Krimm
Other short aliphatic linkers were reported in the case of fragment dimerization, i.e., where two identical fragments binding to separate chains of an oligomeric target are linked, taking advantage of the spatial proximity of the binding pockets. Fragment dimerization was successfully applied to inhibitors targeting the oligomeric form of the pyruvate kinase M2 [13]. Owing to the proximity of the amide moieties of the fragments, linking of the fragments required a simple methylene group. The dimerization reaction was carried out by activating DMSO with DCMT. The best activator molecule showed an AC50 of 3 nM. Similarly, the dimerization of a fragment bound to the AMPA receptor was published [14]. The authors used a Grubbs reaction to join the two identical fragments. The alkene-containing molecule was then reduced to a two-carbon aliphatic chain, resulting in a 13.4 nM ligand.
Identification and characterization of protein cross-links induced by oxidative reactions
Published in Expert Review of Proteomics, 2018
Per Hägglund, Michele Mariotti, Michael J. Davies
Addition of nucleophiles to DHA and DHB can give rise to a number of cross-linked species [57]. Addition of Cys, via Michael addition, to DHA gives the thioether species lanthionine (LAN; 3,3ʹ-thiodialanine), reaction with the side-chain amine of Lys gives lysinoalanine (LAL), and reaction with the imidazole ring of protein-bound histidine results in two histidinoalanine isomers (3-Nτ- and 3-Nπ-histidinoalanine, typically in ratio of ~ 8:1), depending on the nitrogen that reacts. These products have been detected, for example, in proteins subject to high pH conditions (e.g. during alkaline processing of milk proteins [57,120]) and in crystallin proteins of the human lens [121]. The corresponding reactions of DHB occur to a much more limited extent, due partly to the much slower rate of formation of this species from parent Thr/phosphoThr, and also a greater stability of this alkene.
Composition of aerosols from thermal degradation of flavors used in ENDS and tobacco products
Published in Inhalation Toxicology, 2022
Philip J. Kuehl, Jacob D. McDonald, Derek T. Weber, Andrey Khlystov, Matthew A. Nystoriak, Daniel J. Conklin
Eugenol (4-allyl-2-methoxyphenol) is the main constituent of several essential oils of clove (Bhuiyan et al. 2010). The primary degradation products of eugenol were vanillin (4-hydroxy-3-methoxybenzaldehyde), 2,4-dimethylbenzoic acid and 2-3 ring PAHs (naphthalene and acenathylene). Notably, eugenol is often used as a precursor of vanillin through chemical or biotransformation, and thus, vanillin formation was unsurprising. In fact, isomerization of eugenol double bond and oxidation of isoeugenol is described (Lampman et al. 1977). Additional constituents result from the oxidation and aromatization. High temperature formed vanillin and benzene as well as low molecular weight VOCs (e.g. formaldehyde and acetaldehyde). Volatile aromatic organics were produced in similar concentrations by high and low temperature, but these were more minor constituents compared with the low molecular weight alkenes and alkanes.
Related Knowledge Centers
- Cyclic Compound
- Functional Group
- Hydrocarbon
- Organic Chemistry
- Polyene
- Carbon
- Terminal Alkene
- Preferred Iupac Name
- Open-Chain Compound
- Homologous Series