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Introduction to disorders of fatty acid oxidation
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Specific acylCoA dehydrogenases (ACADs) with overlapping specificities for chain length include: short-chain acyl CoA dehydrogenase (SCAD) (Chapter 42), medium-chain acyl CoA dehydrogenase (MCAD) (Chapter 39), and very long-chain acyl CoA dehydrogenase (VLCAD) (Chapter 40). In addition, a tri-functional enzyme catalyzes 3-hydroxyacyl dehydrogenation, 2-enoyl-CoA hydration, and 3-oxoacylCoA thiolysis [7]. Long-chain hydroxyacyl CoA dehydrogenase (LCHAD) is now known to be one of these three enzymatic steps of the tri-functional protein (Chapter 41).
Liposomes
Published in Danilo D. Lasic, LIPOSOMES in GENE DELIVERY, 2019
Although pH-sensitive liposomes can be made from mixtures of lecithins and fatty acids, by far the most common lipid is dioleoyl phosphatidylethanolamine (DOPE). These molecules can form lamellar phases only at higher values of pH when the amine group is charged. By lowering pH it deprotonates; this decreases its polar head area (a) as a result of reduced hydration, and packing parameter P increases from around 1 to a higher value which prefers packing into a hexagonal array. As a consequence, DOPE liposomes become unstable at pH values below 8. Because this pH range is normally not suitable for in vivo applications it is usually used in mixtures with hemisuccinate lipids. In this composition negatively charged cholesterol hemisuccinate protonates at lower pH values and decreases polar head group area. Reduced packing parameter P causes liposome destabilization at pH values below 5.5. As a consequence, liposomes can fuse with nearby membranes or disintegrate and flocculate. Similar release of entrapped material can be achieved if DOPE is packed with lipids with P ~0.5, such as polymer-bearing lipids, and polymer either slowly breaks away by hydrolysis or thiolysis (Kirpotin et al., 1996) or these lipids dissociate from the bilayer due to higher aqueous solubility. The mean value of packing parameter 〈P〉 increases, and above critical value liposome disintegrates (see Figure 6-7). If the mean value of 〈P〉 decreases, such as upon cleavage of double-chain surfactant into two single chain amphiphiles, liposome disintegration follows as well, as schematically shown in Figure 6-7.
Cranberry Proanthocyanidins (PACs) in Bacterial Anti-Adhesion
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Thomas Brendler, Gunter Haesaerts
The average degree of polymerisation of PACs differs and is variably reported as 4.7 (Foo et al. 2000a), 8.5–15.3 (Gu et al. 2003) and up to 23 (Reed et al. 2005; Blumberg et al. 2013), in part due to variable findings using different analytical methods that employ thiolysis and pholoroglucinolysis (Karonen et al. 2007; Zhou et al. 2011). The quantity of PACs found in cranberries can vary, partly due to variations in samples and to differences in analytical methodologies. Gu et al. (2004, using HPLC) reported a PAC content of 418.8 ± 75.3 mg/100 mg in fresh fruit and 231 ± 2 mg/L in cranberry juice cocktail, although different values would be detected using other analytical methods. In both matrices, the majority of the PAC had a >10 degrees of polymerisation.
Redox-triggered mitoxantrone prodrug micelles for overcoming multidrug-resistant breast cancer
Published in Journal of Drug Targeting, 2018
Hongzhi Qiao, Zhenzhu Zhu, Dong Fang, Yuan Sun, Chen Kang, Liuqing Di, Lei Zhang, Yahan Gao
In summary, an amphiphilic TPGS-based MTO prodrug was developed by conjugating MTO to TPGS via a disulphide bond. The resulted prodrug was able to self-assemble into micelles (TSMm) with modest size and surface properties. The designed prodrug micelles rendered excellent stability in the physical conditions and could release MTO via thiolysis at the high concentration of GSH within the tumorous cytoplasm, giving rise to higher cytotoxicity and apoptosis-promoting activity. Moreover, we demonstrated that TSMm could remarkably increase the intracellular concentration and retention of MTO by redox-triggered release and the reduction of the drug efflux rate. Depletion of cellular ATP by TSMm treatment probably accounts for the reversal of drug-resistant phenotype and re-sensitization of the resistant cell lines to MTO. Importantly, TSMm showed high tumour accumulation and excellent antitumor effect in the MDA-MB-231/MDR xenograft model with only negligent side effects. These results indicate that TSMm could have significant advantages for the treatment of drug-resistant breast cancer and deserves further investigations.