Molecular Aspects of the Activity and Inhibition of the FAD-Containing Monoamine Oxidases
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
The two monoamine oxidase isoenzymes, MAO A and MAO B, are encoded by genes on the X-chromosome (MAOA and MAOB) and are expressed in all tissues. In addition to their well-known role in the brain, peripheral MAOs especially in gut (MAO A), liver (both), platelet (MAO B) and placenta (MAO A) play significant roles in protection against biogenic amines and contribute to Phase 1 drug metabolism. In heart, hydrogen peroxide and aldehydes produced by MAO oxidation of amines may contribute to heart failure. These flavoprotein oxidases (E.C. 1.4.3.4) are located on the mitochondrial outer membrane, and therefore metabolize intra-cellular amines. In contrast, the copper-dependent primary amine oxidases (the soluble semicarbazide-sensitive amine oxidase (SSAO) and its membrane form, Vascular Adhesion Protein-1, E.C. 1.4.3.21) act on extra-cellular amines and function in inflammation (Becchi et al., 2017). SSAO, lysyl oxidase (1.4.3.13) and diamine oxidase (E.C. 1.4.3.22 which metabolizes histamine) contain 2,4,5-trihydroxyphenylalaninequinone as the cofactor (www.brenda-enzymes.org). These non-FAD enzymes will not be considered in this article. Other FAD–containing oxidases include the related amino acid oxidases, l-amino acid oxidase (LAAO, E.C. 1.4.3.2) and D-amino acid oxidase (DAAO, E.C. 1.4.3.3), and the spermine metabolizing enzyme, polyamine oxidase (E.C. 1.5.3.13), all of which have covalently bound FAD. A possible evolutionary precursor of MAO is found in the peroxisomes of Aspergillus niger and has a non-covalently bound FAD co-factor (Sablin et al., 1998) making it interesting for chemical applications (Bailey et al., 2007).
Future Strategies for Commercial Biocatalysis
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Ward and coworkers have developed biocompatible, artificial metalloenzymes by supramolecular incorporation of biotin-anchored metal complexes within the core of the protein, streptavidin (France et al., 2017; Groeger and Hummel, 2014; Rudroff et al., 2018). An artificial transfer hydrogenase was constructed by anchoring an iridium complex in the streptavidin core (Koehler et al., 2013). The artificial transfer hydrogenase and a monoamine oxidase were successfully coupled in a chemoenzymatic cascade, which was not possible with the free, transition metal catalyst and enzyme due to mutual inactivation. This concept was expanded to include other enzymes in the concurrent, chemoenzymatic synthesis of l-pipecolic acid from l-lysine (Fig. 1.11). l-Lysine was oxidised by a l-amino acid oxidase and then reduced by the artificial transfer hydrogenase, using formate as the hydride source, producing l-pipecolic acid. Two other enzymes, d-amino acid oxidase and catalase, were included to increase the enantiomeric excess of l-pipecolic acid and to decompose the hydrogen peroxide produced in the amino acid oxidase reactions, respectively. The coupling of l- and d-amino acid oxidases with an artificial transfer hydrogenase to produce l-pipecolic acid from l-lysine.Adapted from France et al. (2017).
Biology and Distribution of Venomous Snakes of Medical Importance and The Composition of Snake Venoms
Jürg Meier, Julian White in Handbook of: Clinical Toxicology of Animal Venoms and Poisons, 2017
The yellow colour of many snake venoms is due to riboflavin, which is present in the form of flavine mononucleotide (FMN) and forms the prosthetic group of venom L-amino acid oxidase171,172. Recently, it has been shown that the L-amino acid oxidase present in many snake venoms has antibacterial activity 173,174.
Prediction of novel inhibitors for Crotalus adamanteus
l -amino acid oxidase by repurposing FDA-approved drugs: a virtual screening and molecular dynamics simulation investigation
Published in Drug and Chemical Toxicology, 2021
Mostafa Khedrinia, Hassan Aryapour, Manijeh Mianabadi
Snakes venom are complex mixtures of enzymatic and non-enzymatic proteins, organic and inorganic compounds (Ramos and Selistre-De-Araujo 2006). One of these enzymes is l-amino acid oxidase (LAAO) with the systematic name of l-amino-acid: oxygen oxidoreductase (EC: 1.4.3.2), which is widely found in various organisms such as insects (Ahn et al.2000), fungus (Nuutinen et al.2012), bacteria (Geueke and Hummel 2002, Yu and Qiao 2012, Matsui et al.2014), plants (Cooper and Pinto 2005, Yang et al.2012), algae (Schriek et al.2009), mammals (Nakano and Danowski 1965, Puiffe et al.2013), and snakes (Li et al.1994, Du and Clemetson 2002, Samel et al.2006, 2008, Costa et al.2014, Izidoro et al.2014). l-Amino acid oxidase catalyzes the oxidative deamination of the l-type enantiomer of amino acids to produce ammonia and α-keto acid via an intermediate imino acid (in accordance with the following reaction) (Bordon et al.2015).
Quantitative proteomic analysis of venom from Southern India common krait (Bungarus caeruleus) and identification of poorly immunogenic toxins by immune-profiling against commercial antivenom
Published in Expert Review of Proteomics, 2019
Aparup Patra, Abhishek Chanda, Ashis K. Mukherjee
The enzymatic activities and pharmacological properties of SI B. caeruleus venom were assessed at a fixed amount of SI B. caeruleus venom protein (10 µg). L-kynurenine was used as a substrate for assaying L-amino acid oxidase (LAAO) activity, as described previously [20,32]. The ATPase, ADPase, and AMPase activities of SI B. caeruleus venom were assayed using ATP, ADP, and AMP, respectively, as substrates. One unit of ATPase/ADPase/AMPase activity was defined as micromoles of Pi released per min at 37°C [20]. Hyaluronidase activity was assayed by the turbidometric method, according to the protocol of Pukrittayakamee et al. (1988) [33] with slight modification, as described by Kalita et al. (2017) [26]. One unit of hyaluronidase activity was defined as a 1% decrease in turbidity, compared to the control, and activity was expressed as U/mg protein. A turbidometric method using egg yolk as substrate was used to assay phospholipase A2 (PLA2) activity [34,35], where one unit of PLA2 activity was arbitrarily defined as a 0.01 decrease in absorbance at 740 nm after 10 min of incubation [34,35].
Proteomics analysis to compare the venom composition between Naja naja and Naja kaouthia from the same geographical location of eastern India: Correlation with pathophysiology of envenomation and immunological cross-reactivity towards commercial polyantivenom
Published in Expert Review of Proteomics, 2018
Abhishek Chanda, Aparup Patra, Bhargab Kalita, Ashis K. Mukherjee
The enzymatic activities of NnV and NkV were assessed using 10 µg venom protein samples. Briefly, phospholipase A2 (PLA2) activity was assayed by the turbidometric method using egg yolk as substrate [24]. One unit of PLA2 activity was defined as a decrease of 0.01 absorbance at 740 nm post 10 min of incubation [24]. For assaying the L-amino acid oxidase (LAAO) activity L-kynurenine was used as a substrate [25]. The LAAO activity (units of activity) was defined as nmol of kynurenic acid produced/min under the assay conditions [25]. Snake venom metalloprotease (SVMP) activity was assayed using azocasein as the substrate. The activity was checked by the spectrophotometric method and specific activity was expressed as ΔA450 nm/min/mg protein [14]. Acetylcholinesterase (AChE) activity was determined spectrophotometrically using 1 mM acetylthiocholine iodide as the substrate [26]. Enzyme activity was defined as micromoles of thiocholine formed per min under the assay conditions. Phosphodiesterase (PDE) activity was assayed using bis-p-nitrophenyl phosphate as substrate, as originally described by Sulkowski and Laskowoski [27] with minor modifications described by us [12]. One unit of PDE activity was expressed as micromoles of p-nitrophenol released per min (using 17,600 as the molar extinction coefficient of bis-p-nitrophenyl phosphate). The phosphohydrolase activity against adenosine tri-phosphate (ATP) and adenosine di-phosphate (ADP) was assayed following the method of Williams and Esnouf [28] with minor modifications as described by us [4]. Adenosine monophosphate (AMP)/5ʹ-nucleotidase (5ʹ-NT) activity was assayed as described previously [12,18,20]. One unit of ATPase/ADPase/AMPase (NT) activity was defined as micromoles of Pi released per min at 37°C [4].
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