Synthesis of Important Chiral Building Blocks for Pharmaceuticals Using Lactobacillus and Rhodococcus Alcohol Dehydrogenases
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
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.
Miscellaneous poisons
Jason Payne-James, Richard Jones in Simpson's Forensic Medicine, 2019
Like ethanol, methanol can cause fatal central nervous system (CNS) depression. Methanol intoxication is an uncommon but serious poisoning. Its adverse effects are due primarily to the impact of its major metabolite formic acid and lactic acid resulting from cellular hypoxia. All of these processes occur in the liver. Formic acid (formate) is toxic because it inhibits mitochondrial cytochrome c oxidase, causing hypoxia at the cellular level. Symptoms including abdominal pain and loss of vision can appear a few hours to a few days after exposure, reflecting the time necessary for accumulation of the toxic byproduct. Methanol also causes metabolic acidosis. Methanol poisoning most often occurs after drinking windscreen-washer fluid, but methanol is also used in copy machines and can be found in many other products, even embalming fluid. Methanol poisoning still remains a well-known consequence of ‘moonshine’ liquor ingestion, although this practice is increasingly uncommon. When paediatric poisoning occurs, it is usually the result of having ingested methanol-containing household products. Ingestion of even small amounts of methanol, in addition to causing profound metabolic acidosis, may lead to blindness or even multiorgan failure and death.
Collagenolysis
Robert A. Greenwald in CRC Handbook of Methods for Oxygen Radical Research, 2018
Using an electron accelerator, it is possible to generate oxy free radicals in high amounts in a very short period.12 The 0.5-M formate solution acts in the same way as in the cobalt bomb irradiation. A pulse radiolysis of 4 nsec under 2.4 × 108 eV generates 10−4M O2− and 10−5M H2O2. Electron accelerator devices usually contain a spectrophotometric system permitting one to measure the absorbance at 245 nm in the cell, allowing monitoring of the amount of superoxide formed. In the experience of the authors, when the suspension of collagen fibrils averages a concentration of 1 mg/mℓ, it does not prevent this monitoring. The cell does not need to be thermostated provided that the experiments are performed within a few seconds, and that the collagen suspension is stored ready for use at 37°C.
Acute and sub-acute toxicity study of ethanol extract from Nectandra leucantha Nees & Mart. (Lauraceae) barks
Published in Drug and Chemical Toxicology, 2023
July Silva Ferreira, Alanne Lucena de Brito, Silvana Tavares Paz, Humberto de Moura Barbosa, Jeymesson Raphael Cardoso Vieira, Carla Mirele Tabósa Quixabeira, Dayane Aparecida Gomes, Pamela Noemy L. Ramirez, Fernanda S. de Sousa, João Henrique G. Lago, Eduardo Carvalho Lira
HPLC analysis of a crude extract from N. leucantha barks (EENl) was carried out with 1 mg/mL in MeOH. HPLC/HRESIMS data were recorded on a Shimadzu® Nexera X2 system equipped with an SPD-M20A Proeminence Diode Array detector (DAD) and coupled to a quadrupole time-of-flight mass spectrometer (MicroTOF-QII®) using an ESI ion source operating in positive ion mode. The mass analyzer was operated in scan mode in the range m/z 100–500 Da. Accurate mass calibration was obtained using a solution of sodium formate (10 mM) as an internal standard. HPLC separation was performed using a Kinetex C18 column (5 μm, 100 Å, 150 × 4.6 mm, Phenomenex) and eluted with a gradient from MeOH:H2O 1:1 (0 min) to MeOH 100% (35 min), using a flow rate of 1.0 mL/min and diode array ultraviolet (DAD-UV).
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.
A review of methanol poisoning: a crisis beyond ocular toxicology
Published in Cutaneous and Ocular Toxicology, 2020
Peter Pressman, Roger Clemens, Saura Sahu, A. Wallace Hayes
Specifically, with regard to formate, its inhibition of mitochondrial cytochrome a/a3 results in compromise of oxidative phosphorylation and mitochondrial viability. Since there is no effective mechanism for transport of formate out of the eye, visual impairment ensues. With increasing acidosis, formate is also retained in the brain with similar metabolic consequences. Similarly, renal excretion of folate is decreased in acidosis due to tubular transport competition. Full restoration of pH balance with bicarbonate infusion is another mainstay of metabolic recovery. Detoxification of formate to CO2 and water depend on the body’s folate pool, which is rate limiting. Formate also depletes glutathione (GSH), resulting in further oxidative damage. Folinic acid (leucovorin) or folic acid can be administered to catalyse this final step18.