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Toxins in Neuro-Ophthalmology
Published in Vivek Lal, A Clinical Approach to Neuro-Ophthalmic Disorders, 2023
Clinical features of methanol intoxication include nausea, vomiting and abdominal pain. The CNS effects of methanol result from accumulation of formic acid within the optic nerve and leads to flashes of light. It progresses further to scotomas and scintillations. Vision loss is probably caused by interruption of mitochondrial function in the optic nerve which results in hyperemia, edema and optic nerve atrophy. Pupillary response to light is compromised and subsequently lost. Confirmation of diagnosis is by serum methanol level with gas chromatography (>20 mg/dL). Serum levels peak after 60–90 min of ingestion, but these do not correlate with the level of toxicity. Accumulation of formate leads to decrease in pH (<7.2 is a severe intoxication). Imaging findings may be suggestive with bilateral enhancing optic nerves and putaminal necrosis.
Xenobiotic Biotransformation
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
The classic examples of alcohol dehydrogenase-mediated bioactivation are in the toxicity of methanol and ethylene glycol. Formate, a metabolite of methanol, causes toxicity to the retina leading to blindness; and oxalate, a metabolite of ethylene glycol, forms a precipitant in kidney tubules leading to stone formation. Leading to hepatotoxicity, alcohol dehydrogenase converts allyl formate and allyl alcohol to the reactive aldehyde, acrolein (Rees and Tarlow, 1967; Reid, 1972). Since alcohol dehydrogenase has a periportal distribution in the liver, allyl formate and allyl alcohol induce periportal necrosis.
Synthesis of Important Chiral Building Blocks for Pharmaceuticals Using Lactobacillus and Rhodococcus Alcohol Dehydrogenases
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marion Rauter, Simon Krebs, Gotthard Kunze
FDH from Candida boidinii was the first enzyme being used in industrial processes (Kragl et al., 1996; Bommarius et al., 1994; Bommarius et al., 1998; Bommarius et al., 1995; Shaked and Whitesides, 1980). Formate is oxidized to CO2, which makes the process irreversible and shifts the reaction balance to NADH regeneration. However, for many industrial processes the use of FDH is not feasible, due to the low specific activity of 6 U mg−1 (Slusarczyk et al., 2000) and high production costs as well as its sensitivity against organic solvents (van der Donk and Zhao, 2003). In addition, wild-type FDH reduces only NAD+, but not NADP+. Later in 2008, Andreadeli et al. identified a double-mutant with 2 × 107-fold improvement of overall catalytic efficiency of NADP+ reduction and a more than 900-fold decrease of efficiency with NAD+, so that its application with Lactobacillus ADHs became possible.
Assessment of anti-arthritic activity of lipid matrix encased berberine in rheumatic animal model
Published in Journal of Microencapsulation, 2023
Neelu Singh, Amit Kumar Pandey, Ravi Raj Pal, Poonam Parashar, Priya Singh, Nidhi Mishra, Dinesh Kumar, Ritu Raj, Sukhveer Singh, Shubhini A. Saraf
The serum samples obtained from normal control (NC) rats, rat models of rheumatoid arthritis (treated and untreated) were used to prepare the NMR samples as per the previously reported method (Guleria et al.2014). The serum metabolic profiles were measured using standard 1D-1H-CPMG NMR experiments on an 800 MHz FT-NMR spectrometer (Bruker Avance-III equipped with Cryoprobe). Formate was taken as an internal reference and with respect to that concentration levels of selected metabolites (glycine and histidine) were assessed using the NMR suite of commercial software CHENOMX following the procedure as described previously by our research group (Kusum et al.2022). The estimated glycine and histidine levels were used for estimating circulatory Glycine to Histidine Ratio (GHR) levels and compared using modalities of Metaboanalyst 5.0 online software (Pang et al.2021). The circulatory GHR levels were reported as mean values (±SD).
Formaldehyde toxicity reports from in vitro and in vivo studies: a review and updated data
Published in Drug and Chemical Toxicology, 2022
Letícia Bernardini, Eduardo Barbosa, Mariele Feiffer Charão, Natália Brucker
In the human body, due to its water solubility and reactivity, FA could rapidly be diffused in many organs and tissues (Liu et al. 2018b, Leng et al. 2019). After its absorption, FA could spontaneously react with glutathione (GSH) to form hydroxymethylglutathione (HMGSH). The formaldehyde dehydrogenase (FDH) enzyme oxidizes HMGSH to S-formylglutathione (FGSH), which is metabolized by S-formylglutathione hydrolase, producing formate and regenerating reduced glutathione (Reingruber and Pontel 2018). Furthermore, FA also could be oxidized by aldehyde dehydrogenase (ALDH) along with cytochrome oxidase isoenzymes CYP450, including CYP2E1 (Dorokhov et al. 2018). This way, the produced formate can be eliminated in the urine in the form of formic acid, react with other biomolecules, or even be metabolized in carbon dioxide (Peteffi et al. 2016).
Enabling rational gut microbiome manipulations by understanding gut ecology through experimentally-evidenced in silico models
Published in Gut Microbes, 2021
Juan P. Molina Ortiz, Dale D. McClure, Erin R. Shanahan, Fariba Dehghani, Andrew J. Holmes, Mark N. Read
How strains adapt their behaviors under changing environments likewise influences intervention outcomes. Microbial substrate preferences can impact competition dynamics and have been uncovered. For instance, B. thetaiotaomicron prioritizes mannose over other monosaccharides,95 and plant-derived polysaccharides over mucin carbohydrates.96 Similarly, lactate-utilizing bacteria prefer glucose over lactate when both are available.97 These substrate preferences are often strain-specific,98 reflecting differences in metabolic pathways. Strain metabolic output also differs with environmental context. Certain bacteria can generate formate, a common intermediate metabolite, but under specific pH conditions the same microorganisms can further metabolize it and generate gaseous hydrogen instead.99 In situations where formate-producing bacteria are paired with hydrogen-dependent microbes such as Blautia hydrogenotrophica, formate is also further metabolized to acetate and energy harvest is maximized.100 Even in pure culture, the relationship between the factors of substrate availability, cell capability/attributes and the outcome of net metabolite production is complex since they result from multiple causal (and interfering) pathways that vary over time.