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Asymmetric Reduction of C=N Bonds by Imine Reductases and Reductive Aminases
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Matthias Höhne, Philipp Matzel, Martin Gand
The first imine reductases employed for biocatalysis were found in organisms identified from a strain screening for bioreduction of (R)- or (S)-2-methyl-1-pyrroline 1 (Mitsukura et al., 2010). The (R)- and (S)-selective IREDs were then identified from two different Streptomyces sp. strains (Mitsukura et al., 2011; Mitsukura et al., 2013). Their amino acid sequences are similar to enzymes of the 6-phosphogluconate dehydrogenase/3-hydroxyisobutyrate dehydrogenase family of reductases. Most of the IREDs explored for biocatalytic applications belong to this family and were identified by sequence similarity in protein databases (Patil et al., 2018): >150 IREDs have been identified and some of them were studied extensively. Therefore, these enzymes have the widest proven synthetic potential today.
Phosphonic Acids And Phosphonates As Antimetabolites
Published in Richard L. Hilderbrand, The Role of Phosphonates in Living Systems, 2018
To date few attempts have been made to study the activity of (6) and (4). Griffin and Burger65 found (4) to inhibit acetylcholine formation by choline acetylase in the absence of adenosine triphosphate (ATP), although no activity could be found with xanthine oxidase, hyaluronidase, and histidine decarboxylase. Moreover, it was found77 not to interact with glucose-6-phosphate dehydrogenase. For comparison with this latter result, the isosteric system (6) was found77 to be a substrate for glucose-6-phosphate dehydrogenase (from yeast), the product acid (Structure 7) also being a substrate for 6-phosphogluconate dehydrogenase. As yet no nonenzymatic synthesis for (7) has been reported.
Translation and Post-Translational Modifications During Aging
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
It has also been suggested that the loss of 11 lysine residues, presumed due to oxidation, may be the cause of the inactivation of 6-phosphogluconate dehydrogenase in rat livers and human erythrocytes during aging. Similarly, the loss of activity of rat liver malic enzyme during aging is related to the loss of histidine residues by oxidation.146 Furthermore, oxidation of a cysteine residue in glyceraldehyde-3-phosphate dehydrogenase may be responsible for its inactivation during aging in rat muscles.147,148 It has also been reported that the concentration of the oxidation products of human lens proteins and skin collagen increases along with the accumulation of oxidative forms of α-crystallin in patients with age-related cataracts.140 However, the content of ortho-tyrosine and dityrosine, formed by the oxidation of phenylalanine and tyrosine, respectively, did not increase in the aging human lens.149
Mapping the human sperm proteome – novel insights into reproductive research
Published in Expert Review of Proteomics, 2023
Mika Alexia Miyazaki, Raquel Lozano Guilharducci, Paula Intasqui, Ricardo Pimenta Bertolla
Sperm DNA fragmentation (SDF) is an important factor to highlight since it is crucial to embryo development success. In an investigation with LC-MS/MS of men with SDF, 78 differentially expressed proteins were identified. Higher expression of 6-phosphogluconate dehydrogenase, decarboxylating (PGD), Isocitrate dehydrogenase [NADP] cytoplasmic (IDH1) and Ribonuclease H1 (RNH1) was found. These proteins are correlated with antioxidant potential, which suggests that DNA damage caused by oxidative stress is one of the important factors. On the other hand, both Nucleotide excision repair (NER) and Non-homologous end-joining factor (NHEJ), responsible to optimal double-strand break DNA repair, were upregulated which demonstrates the cellular machinery’s attempt to repair the damage. The high levels of Ferritin heavy chain (FTH1) can also moderate the DNA damage since it is commonly increased in response to higher levels of reactive oxygen species [85].
Investigation of the effects of cephalosporin antibiotics on glutathione S-transferase activity in different tissues of rats in vivo conditions in order to drug development research
Published in Drug and Chemical Toxicology, 2020
Fikret Türkan, Zübeyir Huyut, Parham Taslimi, Mehmet Tahir Huyut, İlhami Gülçin
In recent years, inhibition studies of many antibiotics have been performed extensively. These studies were conducted on various enzymes, including paraoxonase (Demir and Beydemir 2015, Türkeş et al.2015). glucose-6-phosphate dehydrogenase (Ozmen et al.2005), 6-phosphogluconate dehydrogenase (Akyüz et al.2004), glutathione reductase (Erat et al.2005), and glutathione S-transferase (Comakli et al.2011). In vivo results from the enzyme activity studies are crucial to recognize the physiological role of the enzyme. Particularly, drug-enzyme or any chemical compound-enzyme interaction studies are important to understand the toxicological mechanisms. In present study, we evaluated cefazolin, cefuroxime, and cefoperazone in vivo inhibition effect on GST enzyme activity. In cefazolin and cefoperazone groups, GST enzyme activities were increased in liver and renal tissues during the first 5 h period, and then began to drop in the next time period. In addition, they were increased in cefuroxime group during firs 3 h period, while began to drop in the next time periods. The situation was showed that the cefazoline and cefaperazon were metabolized after 5th hour and completed their half-life, while cefuroxime were metabolized after 3th hour on GST activity. In addition, after 7 h, it was observed that cefazolin had no adverse effect on GSH enzyme activity in all working tissues, but cefuroxime and cefaperazon caused the decreasing in GST activities compared to control groups after 5th hour period.
Hyperosmolar Potassium Inhibits Corneal Myofibroblast Transformation and Prevent Corneal Scar
Published in Current Eye Research, 2023
Kai Liao, Zekai Cui, Zhijie Wang, Yu Peng, Shibo Tang, Jiansu Chen
To elucidate the antifibrotic mechanism of potassium, we conducted an RNA sequencing study. RNA sequencing results revealed that 1516 genes were differentially expressed between the KCl and control groups. The number of upregulated and downregulated DEGs was similar. According to the results of the top 20 significantly enriched KEGG pathways, we focused on metabolic pathways, Rap1 signaling pathway, and apoptosis pathway. PGD and PTGES were selected from the metabolic pathways. PGD (6-Phosphogluconate dehydrogenase) is an key enzyme in the pentose phosphate pathway, then, indirectly involved with ATP productin in glycolysis pathway.23 An increasing body of evidence suggests that PGD is upregulated in many solid cancers,24–26 and PGD activity inhibition can inhibit cell proliferation and tumor growth.27 In addition, in a rat model of pulmonary fibrosis induced by bleomycin, upregulated expression of PGD was found, and PGD activity inhibition resulted in an antifibrotic effect.28 Furthermore, studies have shown that knocking out PTGES can promote liver repair after liver injury in mice.29 PTGES (Prostaglandin E Synthase) is an enzyme in the prostaglandin E synthase pathway. ATP could stimulate arachidonic acid release and the synthesis of prostaglandin E2.30 In the present study, PGD and PTGES in the KCl group were significantly downregulated compared with the control group, suggesting that potassium may exert an antifibrotic effect by inhibiting the expression of PGD and PTGES via regulating ATP production. In addition, our results showed that PGD inhibitor could inhibit corneal myofibroblast transformation in cell culture. These results suggested that metabolic intervention could regulate the process of corneal fibrosis. Besides, our results showed that ATP levels were significantly decreased in the KCl group, indicating that potassium may inhibit corneal myofibroblast transformation by inhibiting cell metabolism.