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Cell Biology for Bioprocessing
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
In addition to their role in energy metabolism, mitochondria also play a key role in the regulation of apoptosis. Some pro-apoptotic proteins are sequestered in the space between the outer and inner membranes of mitochondria. Cytochrome C, a hemeprotein that is an important component of the cytochrome C complex in the electron transport chain, is associated with the inner membrane of mitochondria. The release of cytochrome C and those pro-apoptotic proteins in stressed cells initiates the intrinsic pathway of apoptosis (Figure 2.22). The cytochrome C released into the cytoplasm proceeds to form a complex with APF1, pro-caspase 9, and dATP, known collectively as the apoptosome. In the apoptosome, the inactive pro-caspase 9 becomes activated and subsequently activates downstream caspases.
Conversion of Natural Products from Renewable Resources in Pharmaceuticals by Cytochromes P450
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Giovanna Di Nardo, Gianfranco Gilardi
Cytochromes P450 are a large superfamily of heme-containing monoxygenases mainly acting as hydroxylases. The large number of members of this superfamily, their wide distribution in nature, and their ability to carry out different oxidation reactions on thousands of substrates make these enzymes highly interesting in the field of biocatalysis. Moreover, the physiological role of these enzymes in different organisms such as bacteria, fungi, and plants is the synthesis of natural compounds that have been used themselves as drugs or as molecular leads for the development of other active compounds. In mammals, cytochromes P450 physiologically act as the main enzymes involved in Phase-I drug metabolism as well as pro-drug activation. Thus, nature has already provided a panel of enzymes suitable to modify many molecules with different molecular scaffolds and biological activities. The knowledge on this enzymatic pool is continuously growing thanks to the progresses in genome sequencing of different organisms that provides new P450 gene sequences, new substrates and reaction carried out.
Biocatalytic Nanoreactors for Medical Purposes
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Oscar González-Davis, Chauhan Kanchan, Rafael Vazquez-Duhalt
Cytochrome P450 (CYP). So far, chemotherapy is the most used therapy for cancer (Al-Lazikani et al., 2012). There are almost 200 different cytotoxic compounds that are currently available for this use (Huttunen et al., 2008), most of them administered as prodrugs, which have to be transformed into the active anticarcinogenic drug. This transformation is mainly performed by the cytochrome P450 superfamily (Huttunen et al., 2008). When administered, most of these prodrugs are activated in the liver, where CYPs are overexpressed (Bièche et al., 2007). On the other hand, CYP expression varies significantly in the different tissues (Choudharya et al., 2003), and even more, in some cases healthy cells near the tumor cells express higher CYP activity (Zhao et al., 2012), in which the cytotoxic agent is preferentially activated affecting these healthy cells.
Green hydrogen production by Rhodobacter sphaeroides
Published in Energy Sources, Part A: Recovery, Utilization, and Environmental Effects, 2023
Dahbia Akroum-Amrouche, Hamza Akroum, Hakim Lounici
During respiration, cytochromes b and c (common components of photosynthesis and respiration) are preserved, while bacteriochlorophylls and carotenoids are inhibited. In the presence of oxygen, cytochrome c2 transfers the electrons from ubiquinone-cytochrome c2 oxidoreductase (the cytochrome b-c1 complex) to terminal cytochrome α-a3 oxidase. Under photosynthetic conditions, cytochrome c2 functions to complete the cyclic photophosphorylation chain by the transfer of electrons from the cytochrome b-c1 complex to reduce the photo-oxidized reaction center (Brandner et al. 1989; Lancaster and Michel 1996), (Figure 3).
Interactions of α -Lactalbumin and Cytochrome c with Langmuir Monolayers of Glycerophospholipids
Published in Journal of Dispersion Science and Technology, 2011
Wilhelm R. Glomm, Sondre Volden, Marit-Helen Glomm Ese, Øyvind Halskau
Bovine α-lactalbumin (α-La) is a 14.2 kDa globular calcium-binding milk protein which is a component of the lactose synthase complex. α-La binds to galactosyltransferase, promoting glucose binding and facilitating the synthesis of lactose in lactating mammary glands.[18] Previous in vitro studies have shown that α-La adopts a molten globular-like conformation when it interacts with membranes.[1-5] Cytochrome c (Cyt c) shuttles electrons between the two membrane-associated protein complexes cytochrome c reductase and cytochrome c oxidase on the inside of the inner mitochondrial membrane, and is a part of the mitochondrial production of ATP. It has been established using fluorescence measurements of monolayers[19] and solid-state 31P NMR[20] that Cyt c binds specifically to anionic phospholipids. Moreover, Cyt c has been demonstrated to form stable molten globules both at electrodes set up to mimic the in vivo redox reaction,[21] in association with anionic membranes, and in bulk solution.[12,22-25] Thus, the two proteins are both globular and mostly helical, amphitropic proteins of similar size and share the trait of being able to partially unfold as they interact with membranes and surfaces. Their charge properties are different, however, with α-La being an acidic while Cyt c being a basic protein. Herein, we address whether proteins and their trapped folding states can intercalate into already formed phospholipid monolayers, as well as the importance of global protein charge for interaction.
The inhibitory effect of some natural bioactive compounds against SARS-CoV-2 main protease: insights from molecular docking analysis and molecular dynamic simulation
Published in Journal of Environmental Science and Health, Part A, 2020
Doaa A. Abdelrheem, Shimaa A. Ahmed, H. R. Abd El-Mageed, Hussein S. Mohamed, Aziz A. Rahman, Khaled N. M. Elsayed, Sayed A. Ahmed
Lipinski’s rule of five is commonly utilized in development and drug design to expect oral bioavailability of drug molecules. Lipinski’s rule was established based on five rules to compute the ability of the compound to act as an orally active drug was calculated and shown in Table 6. So, orally active drugs must have no more than one violation of the following standards: (i) octanol/water partition coefficient (log P) which measured the lipophilicity of a molecule must be not greater than five. (ii) A molecular weight (MW) less than 500 Da. (iii) not more than five hydrogen bond donors (nON). (iv) not more than 10 hydrogen bond acceptors (nOHN). The topological polar surface area (TPSA) is measured the bioavailability of the drug molecule. TPSA is closely related to the hydrogen bonding potential of a compound. TPSA of studied compounds was noticed in the range of 25.87–153.50 Å and is well below the limit of 160 Å. It can be predicted that all studied bioactive compounds obeyed Lipinski’s rule of five and are likely to be orally active except compounds 5 and 9 as shown in Table 6. The database supports ADMET profiles which involve some features to study the ability of the studied compounds to act as drug leads such as Blood–brain barrier (BBB) penetration, human intestinal absorption (HIA), Caco-2 cell permeability, CYP inhibitory promiscuity, AMES toxicity, carcinogenicity, and rat acute toxicity LD50 are calculated and displayed in Table 7. As shown in Table 6, all studied compounds may cross blood brain barrier (BBB) and absorb in the human intestine (HIA) along are permeable for Cacoe2 cells, whereas, compound 5 showed a negative result for BBB, HIA, and Cacoe2 cell permeability. Cytochrome P450 (CYP) is a group of isozymes containing the metabolism of drugs, steroids, fatty acids, bile acids, and carcinogens. The results indicate that these studied compounds are non-substrate and non-inhibitor of CYP enzymes.[13,60] In terms of AMES toxicity, all studied compounds were observed to be non-toxic. Carcinogenicity model indicated non-Carcinogenic nature of all studied compounds. Rat Acute Toxicity LD50 of all studied compounds was found between 1.95 and 2.75 mol/kg. The finding strongly provides the ability of most of all studied compounds to act as a drug, except compound 5 as shown in Table 7.