Radiolabeled Enzyme Inhibitors for Imaging
Lelio G. Colombetti in Principles of Radiopharmacology, 1979
In 1970, Goldman9 studied the tissue distribution of 17β-hydroxy-4, 4’-17α-trimethylandrost-5-en-[2,3d]-2-14C-isoxazole (isoxazole), a radiolabeled irreversible enzyme inhibitor of 3β-hydroxysteroid dehydrogenase and Δ5-4, 3-ketosteroid isomerase in the rat. Twenty-four hours after a single dose, the label was present in the adrenals, ovaries, and liver. Beyond 48 hr, the label was retained only by the adrenals and ovaries, where it remained for 13 weeks. The labeled compound, extracted from adrenal homogenates, had a mobility identical to that of standard isoxazole on silica gel in 3 chromatographic systems, and an inhibitory capacity similar to the isoxazole standard in a bacterial 3β-hydroxysteroid dehydrogenase assay system. Inhibition of enzymatic activity in vivo was directly correlated with uptake of the label. Return of enzymatic activity correlated with disappearance of label; the degree of enzymatic inhibition and amount of label in both glands attaining constant low values after about 1 month. These observations provided evidence for the specificity of action of this analog and suggested that its long-term effects are a function of its selective and tight binding to the active sites of hydrogenase and isomerase.
Leveraging Genome Sequencing Strategies for Basic and Applied Algal Research, Exemplified by Case Studies
Gokare A. Ravishankar, Ranga Rao Ambati in Handbook of Algal Technologies and Phytochemicals, 2019
In this way, the research in photosynthesis has been expanded aiming for the development of methods for the production of photobiological hydrogen in green microalgae such as C. reinhardtii (Melis 2007; Mus et al. 2007; Nguyen et al. 2008). Some studies have demonstrated that it is possible to produce photobiological H2, reducing the size of the light sensing antenna, and inhibiting state transitions and hydrogenase engineering (Hankamer et al. 2007; Melis 2007). In combination with physiological and biochemical approaches, these studies allowed a greater understanding of H2 metabolism and maturation of hydrogenase enzymes in green microalgae. In this context, knowledge of metabolism coupled with genetic tools provides the emergence strategies to optimize the production of H2 eukaryotic photosynthetic organisms (Radakovits et al. 2010).
An Overview of Parasite Diversity
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2023
Additionally, one noteworthy stramenopile (one lacking flagella) is of the genus Blastocystis, for which several subtypes are known, some of which have been recovered from humans and are then referred to as Blastocystis hominis (Figure 2.8A). These organisms have the distinction of colonizing over 1 billion people, making them the most prevalent eukaryotic microbe infecting the human intestine. They are probably transferred between humans and domestic animals and have been implicated in causing diarrhea and nausea. Blastocystis has also been associated with cases of irritable bowel syndrome and may pose problems for immunocompromised people. Their role in causing pathology remains controversial and they are often considered components of a healthy gut microbiome. As with many eukaryotes inhabiting anaerobic or microaerophilic portions of the gut, Blastocystis does not possess conventional mitochondria capable of aerobic respiration. It has a mitochondrion-like organelle that does generate adenosine triphosphate (ATP) but seems intermediate in function between a mitochondrion and a hydrogenosome. The latter is an organelle that generates ATP from pyruvate, while giving off hydrogen (H2) as a by-product. Blastocystis has a hydrogenase enzyme but does not produce H2.
Bile acid oxidation by Eggerthella lenta strains C592 and DSM 2243T
Published in Gut Microbes, 2018
Spencer C. Harris, Saravanan Devendran, Celia Méndez- García, Sean M. Mythen, Chris L. Wright, Christopher J. Fields, Alvaro G. Hernandez, Isaac Cann, Phillip B. Hylemon, Jason M. Ridlon
Additional gene clusters encoded by model acetogens, including membrane-spanning electron transport chains such as the Clostridium ljungdahlii proton-translocating ferrodoxin:NAD+ oxidoreductase (Rnf)45 were found in both E. lenta DSM 2243 (Elen_0694-0698) and E. lenta strain C592 (CAB18_RS4340-4360). We located Elen_0690 (3α-HSDH) immediately downstream and within the same operon of the Rnf complex in E. lenta DSM 2243 previously determined to have bile acid 3α-HSDH activity.12 An energy-conserving hydrogenase (Ech)46 was also located in E. lenta DSM 2243 (Elen_1570-1575) and E. lenta strain C592 (CAB18_RS07980-7960). In addition, both strains harbor ATP synthase transmembrane complexes, able to utilize this proton gradient generated from Rnf and Ech complexes to generate ATP from ADP.
Radioprotective effect of atorvastatin against ionizing radiation-induced nephrotoxicity in mice
Published in International Journal of Radiation Biology, 2018
Fereshteh Talebpour Amiri, Maedeh Hamzeh, Ramezan Ali Naeimi, Arash Ghasemi, Seyed Jalal Hosseinimehr
IR generates ROS and imbalances in pro-oxidant/antioxidant status which results in oxidative stress (Bhosle et al. 2005). The excessive production of free radicals with lipid peroxidation induced leakage of cytosolic enzymes such as lactate dehydrogenase, creatinine kinase and phosphatases (Ramadan et al. 1997) and destruction of the cell membrane by lipid peroxidation is an important factor in the development of radiation-induced tissue damage (Valko et al. 2006). Increase of MDA level represented a physiological impairment of the antioxidant status (Karbownik and Reiter 2000). In the present study, the MDA level, as a marker of lipid peroxidation, was increased in irradiated animals. These results are consistent with previous studies (Elkady and Ibrahim 2016; Ismail et al. 2016). In irradiated mice, glutamate de-hydrogenase enzyme increases carbamoyl phosphate synthetase activity and subsequently urea concentration (Ramadan et al. 2001). In this study, IR caused a remarkable increase in the levels of creatinine and urea. Furthermore, the levels of urea and creatinine in irradiated mice pretreated with ATV were significantly decreased when compared with the IR only group. These findings in groups with ATV pretreatment are aligned with the published literature on the antioxidant effects of ATV (Profumo et al. 2014).
Hydrogen cross-feeders of the human gastrointestinal tract
Published in Gut Microbes, 2019
Nick W. Smith, Paul R. Shorten, Eric H. Altermann, Nicole C. Roy, Warren C. McNabb
Hydrogen is a major and efficient electron sink product in the human GIT, alongside other fermentation products such as ethanol, lactate and succinate.11 However, the quantity of hydrogen produced in the GIT is dependent upon the population structure of the microbiota in each individual. The two major phyla of the GIT microbiota are the Firmicutes and the Bacteroidetes, which together form over 85% of the total bacterial population in adults.12,13 The relative proportions of these phyla have been shown to vary between individuals14,15 and according to diet.16 Of the Firmicutes and Bacteroidetes, culture-based studies suggest that free hydrogen is mainly produced by the former (for a review, see ref. 9). The co-culture growth of a Bacteroides strain (Bacteroidetes) with a Ruminococcus strain (Firmicutes) on cellulose resulted in decreased cumulative hydrogen production compared to Ruminococcus monoculture, despite increased overall cellulose degradation.17 Importantly, both strains were able to persist together in this experiment, as is the case in the human GIT. A recent genome survey of 343 sequenced genomes from the Human Microbiome Project found that more than 70% contained hydrogenase-encoding sequences, the majority of which were members of either the Firmicutes or Bacteroidetes phyla.18 This implies that hydrogen cycling within these phyla may be more important than previously thought, but it is unclear how such cycling contributes to the gastrointestinal hydrogen concentration. Nonetheless, the concentration of hydrogen in the GIT will depend in part upon the balance between those bacteria that produce hydrogen during fermentation and those that do not, as shown by the culture-based study.