The Effects of Experimental Diabetes on the Cytochrome P450 System and Other Metabolic Pathways
John H. McNeill in Experimental Models of Diabetes, 2018
The cytochrome P450–dependent mixed-function oxidases are by far the most important enzyme system in the metabolism of xenobiotics. Almost every lipophilic chemical that finds its way into the body is, at least partly, subject to metabolism catalysed by this enzyme system. This versatile oxygenase inserts oxygen into specific sites in organic molecules to make them polar and prepare them for Phase II metabolism. It displays unprecedented substrate specificity, being efficient in metabolising structurally very diverse chemicals, of markedly different molecular shape and size. The metabolic function of the cytochrome P450 system is not confined to xenobiotics, but extends to vital endogenous substrates. It plays an important role in the metabolism of steroid hormones, both in their biosynthesis and catabolism, eicosanoids such as prostaglandins, fatty acids such as arachidonic acid, and vitamins such as vitamins A and D. The cytochrome P450–dependent mixed-function oxidase system comprises an electron transport chain consisting of the flavoprotein cytochrome P450 reductase and the haemoprotein cytochrome P450, which functions as a terminal oxidase (Figure 5.7). It catalyses the incorporation of one atom of molecular oxygen to the substrate (RH) while the second atom forms water.
Biogeneration of Volatile Organic Compounds in Microalgae-Based Systems
Gokare A. Ravishankar, Ranga Rao Ambati in Handbook of Algal Technologies and Phytochemicals, 2019
Many of the compounds detected in microalgae originate from the terpenoid pathways. β-ionone is produced by double-bond cleavage enzymes between carbons 9 and 10 of β-carotene. In addition, β-cyclocitral can be formed from the enzymatic cleavage of the double bond between carbons 7 and 8 of the same carotenoid, catalyzed by β-carotene- oxygenases bound to the cell membrane (Chang et al. 2011; Santos et al. 2016b).
Heme Degradation and Bilirubin Formation
Karel P. M. Heirwegh, Stanley B. Brown in Bilirubin, 1982
During heme catabolism the further reaction of mesohydroxyhemes with molecular oxygen to yield (ultimately) carbon monoxide and the corresponding biliverdin, is generally believed to occur spontaneously, i.e., noncatalytically. If this is so, then the catalytic action of heme oxygenase in biological heme cleavage is limited to the initial hydroxylation step. In this sense heme oxygenase would be a classical mixed function oxygenase, very similar to cytochrome P450, in both cases the heme being required to activate molecular oxygen. The special feature of heme oxygenase would then be reduced to the fact that it is the heme molecule itself which is also the substrate. This view is based primarily on the fact that the oxidation in vitro of pyridine solutions of mesohydroxyhemes by molecular oxygen occurs relatively rapidly in the absence of reducing agent, yielding CO and bile pigment. However, the yields of bile pigment obtained are far from quantitative and several other products including tripyrroles are formed. By contrast, the conversion of administered heme (as hemoglobin) to bilirubin in living rats is very efficient,78 suggesting a more quantitative conversion of the (implied) mesohydroxyheme intermediate to bile pigment in vivo. This raises the important question of why the biological system should convert mesohydroxyheme to bile pigment more efficiently than the chemical system, if both are noncatalytic. An important factor underlying this problem may be the role of reducing agent in the cleavage process. It has recently been shown that, although direct reaction of oxygen with iron(III) octaethyloxophlorin does undoubtedly result in octaethylbiliverdin formation, the yield is almost doubled if the reaction is carried out in the presence of ascorbate.77 If the further oxidation of mesohydroxyheme in vivo occurs with the intermediate still combined with heme oxygenase apoprotein, then presumably additional reducing equivalents would be available for the macrocyclic cleavage step, via the NADPH cytochrome c reductase system. In addition side reactions such as the formation of tripyrroles may be prevented sterically, by the blocking of methene bridge carbon atoms by protein amino acid residues.
Loss of ciliary zonule protein hydroxylation and lens stability as a predicted consequence of biallelic ASPH variation
Published in Ophthalmic Genetics, 2019
Owen M Siggs, Emmanuelle Souzeau, Jamie E Craig
Traboulsi syndrome, also known as FDLAB syndrome (facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs), is a rare ocular malformation syndrome associated with ectopia lentis (2–6). FDLAB syndrome is caused by biallelic variants at the aspartyl/asparaginyl hydroxylase (ASPH) locus (5), which encodes at least three unique proteins: junctin, junctate, and ASPH (7). All variants associated with FDLAB syndrome uniquely affect APSH, which encodes a 2-oxoglutarate-dependent oxygenase enzyme that catalyses C-3 hydroxylation of aspartic acid and asparagine residues in the endoplasmic reticulum (8). The 2-oxoglutarate-dependent oxygenases are a family of non-heme, Fe(2)+-dependent enzymes, and include several essential regulators of oxygen homeostasis via the transcription factor hypoxia-inducible factor (9).
Role of curcumin and its nanoformulations in the treatment of neurological diseases through the effects on stem cells
Published in Journal of Drug Targeting, 2023
Nasim Sabouni, Hadi Zare Marzouni, Sepideh Palizban, Sepideh Meidaninikjeh, Prashant Kesharwani, Tannaz Jamialahmadi, Amirhossein Sahebkar
Regarding the effects of curcumin on mesenchymal stem cells, curcumin has a protective role against H2O2-mediated apoptosis through an HO-1-dependent mechanism that was demonstrated by Wagener et al. Haem oxygenase is an enzyme that catalyses the degradation of haem and generates molecules including biliverdin/bilirubin, carbon monoxide (CO) and ferrous iron. It can mediate anti-oxidative, anti-inflammatory, and anti-apoptotic effects and causes cytoprotective effects likely via CO production. Since MSCs efficacy is damaged by oxidative stress in injured tissue, it was suggested in the mentioned study that curcumin can induce HO-1 to increase ADSC survival after administration to promote their therapeutic properties during the cell therapy process [187]. A recent in vitro work in 2019 reported the immunoregulatory, proliferative, and anti-oxidant effects of nanocurcumin on adipose-derived mesenchymal stem cells. Low doses of curcumin were shown to increase the survival and proliferation of ADSCs and decrease their apoptosis, inflammatory cytokines, and SOD activity [44]. Meanwhile, the proliferative effect of curcumin at low concentrations on adipose tissue-derived MSCs has been indicated in another study by Pirmoradi et al. They reported that curcumin increased the lifespan TERT gene expression level of rADCSs to reduce ageing in these cells [188]. In a study by Jiri Ruzicka1 et al. Co-treatment with MSCs and curcumin as an anti-inflammatory compound was demonstrated synergic effects in the rat model of spinal cord injury (SCI) recovery [189].
Honeyberry-derived carbon quantum dots ameliorate LPS-induced neuroinflammation and oxidative stress through Nrf2/HO-1 signalling in HMC3 cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2023
Sanjay , Anshul Sharma, Hae-Jeung Lee
Generally, haem oxygenase consists of two isoenzymes, inducible form (HO-1) and constitutively expressed form (HO-2), which share sequence homology and similar structures [57]. Though little is known about HO-2, this constitutionally expressed form is highly expressed in the brain, testes, and neural tissues [58]. In this study, the expressions of Nrf2 and downstream protecting genes, including HO-1 and HO-2 were reduced in the presence of LPS. However, CQDs treatment reversed the expression both at mRNA (Figure 6) and protein levels (Figure. 7). In a prior study, the role of gold nanoparticles (AuNPs) in inducing HO-1 production via Nrf2 activation was established [59]. Noticeably, CDs have shown a high ability to pass the blood-brain barrier and target abnormalities such as brain cancer glioma tissue [60]. Thus, these fluorescent carbon dots/CQDs could be utilized as nanomedicine in the near future.
Related Knowledge Centers
- Carbon Monoxide
- Enzyme
- Flavin Adenine Dinucleotide
- Iron
- Oxygen
- Redox
- Substrate
- Oxidoreductase
- Enzyme Commission Number
- Monooxygenase