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Ultratrace Minerals
Published in Luke R. Bucci, Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Borates and other organoboron compounds inhibit two major classes of enzymes — oxidoreductases and serine proteases.1001,1006 In oxidoreductases, boron competes with pyridine or flavin nucleotide cofactors (NADH, NADPH, and FAD).1001 Examples include alcohol dehydrogenase, xanthine oxidase, glyceraldehyde-3-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and cytochrome b5 reductase.1002 Thrombin, chymotrypsin, and subtilisin are known to be inhibited by borate.1001 Other serine proteases are important mediators of inflammation and resulting tissue damage.150 Thus, boron may possess potential antiinflammatory actions by inhibition of enzymes used to promote inflammation, tissue degradation, and leukocyte respiratory burst (free radical formation). However, before any conclusions about the antiinflammatory nature of boron can be made, concentrations for in vitro effects must be matched to localized in vivo levels. The possible antiinflammatory effects of boron compounds deserve further attention.
Genetics and metabolic disorders
Published in Jagdish M. Gupta, John Beveridge, MCQs in Paediatrics, 2020
Jagdish M. Gupta, John Beveridge
3.33 Which of the following inborn errors of metabolism is X-linked in inheritance?Tay Sachs disease.Fabry disease.Glucose-6-phosphate dehydrogenase deficiency.Menkes disease.Lowe syndrome.
Liver Diseases
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Two enzyme systems are involved in the metabolism of alcohol; one is cytosolic, and the other is microsomal. Alcohol and aldehyde dehydrogenases are cytosolic components mainly responsible for the first two steps of alcohol oxidation.57,233,288,544 The second alcohol oxidizing enzyme complex is bound to the microsomal fraction.36,549 Alcohol dehydrogenase is found mainly in the liver. This enzyme is the rate-limiting step in the metabolism of alcohol (Figure 34). In the human liver, there are three to seven active alcohol dehydrogenase isoenzyme fractions with variable activity.280,565,610 The isoenzymes composition varies widely from and with different turnover rates, thus explaining the individual and ethnic variations. Aldehyde dehydrogenase is present in many tissues,564 and several isoenzymes have been identified.234,246,425,474 Animal experiments have shown that with alcohol pretreatment the activity of alcohol dehydrogenase increases. This adaptive change may be important in the development of tolerance in alcoholism.
Improving mitochondrial function in preclinical models of heart failure: therapeutic targets for future clinical therapies?
Published in Expert Opinion on Therapeutic Targets, 2023
Anna Gorący, Jakub Rosik, Joanna Szostak, Bartosz Szostak, Szymon Retfiński, Filip Machaj, Andrzej Pawlik
Mitochondrial dysfunction also leads to increased lipid peroxidation, resulting in the production of highly reactive carbonyls, such as various ketones, alkanes, and aldehydes. A key role in these processes is played by aldehyde dehydrogenase (ALDH2). ALDH2 is involved in the removal and metabolism of exogenous chemicals and endogenous reactive aldehydes to maintain homeostasis and normal mitochondrial function [200]. This enzyme appears to be a promising target for therapy aimed at improving mitochondrial function in patients with HF. In an animal model of HF induced by myocardial infarction, ALDH2 activation was shown to reduce the concentration of reactive aldehydes in cardiomyocytes and limited. Most therapies to date affecting mitochondrial metabolism have focused on single factors or processes disrupted in HF. However, in this disease, there are multidirectional disorders improve mitochondrial bioenergetics [201]. Moreover, sustained ALDH2 activation prevented myocardial hypertrophy, fibrosis, and cardiac dysfunction.
Analysis of clinical characteristics and prognostic factors of ARDS caused by community-acquired pneumonia in people with different immune status
Published in Expert Review of Anti-infective Therapy, 2022
Zhipeng Cheng, Qiang Zhu, Jingyi Chen, Yanan Sun, Zhixin Liang
Lactate dehydrogenase (>396.4 IU/L) and APACHE2 score (>16.5) were independent risk factors for 28-day in-hospital mortality in the immunocompromised group. Lactate dehydrogenase is a key enzyme in cellular metabolic processes and it is present in almost all body cells, with high levels in the heart, liver, lung, muscle, kidney, and blood cells. It has been reported that the increase of serum LDH content has a certain value in the evaluation of ARDS, sepsis conditions, and prognosis [36,37]. In addition, many studies have concluded that serum LDH levels are associated with poor prognosis in immunocompromised patients [38].In the study, we found that serum LDH levels were higher in the immunocompromised group than in the immunocompetent group and the value of LDH was correlated with the prognosis of patients with ARDS, which is consistent with the conclusions of other studies [39],and LDH may be a reliable indicator for prognostic assessment of ARDS in immunocompromised patients. The APACHE II score is the most widely used system for evaluating critical illnesses and contains a variety of critical illness indicators, and most of the current findings suggest that the higher the score, the more severe the disease [40], which is the same as the results of this study. It is worth noting that the APACHE II score will change with the effect of treatment and needs to be evaluated dynamically in real-time, and the score lacks specificity for critical illness, so it is recommended to combine it with patient history and other indicators in clinical practice.
Can we rely on synthetic pharmacotherapy for the treatment of glioblastoma?
Published in Expert Opinion on Pharmacotherapy, 2021
Chibueze D. Nwagwu, David C. Adamson
Disulfiram has been well characterized as one of the few treatments for alcohol dehydrogenase given its inhibition of alcohol dehydrogenase. It was recently repurposed for the treatment of glioblastoma in combination with copper, as this regimen has been shown preclinically to exert anti-tumorigenic activity on glioblastoma stem-like cells [66]. This was done with the rationale that disulfiram can penetrate and chelate Cu intracellularly in GBM stem-like cells, which propagate the self-renewing phenotype crucial for GBM heterogeneity [67,68]. Given that the action of disulfiram is heavily dependent on Cu, high Cu concentration in cancer cells may serve as attractants for disulfiram action specifically in cancer cells, consequently sparing normal tissues [67,68]. Disulfiram in combination with copper was evaluated in glioblastoma patients treated with radiotherapy and TMZ [66]. Fourteen percent of the patients had median PFS of 1.7 months, and median OS at 7.1 months [66]. A subset of glioblastoma patients with IDH1, BRAF, or NF1 mutations had significantly improved PFS and OS in contrast to those patients lacking these mutations [66]. It is important to mention that these results were extrapolated from a conference paper and clinical benefit or lack thereof cannot be readily deduced from the results presented.