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Role of Tandem Mass Spectrometry in Diagnosis and Management of Inborn Errors of Metabolism
Published in P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas, Advanced Studies in Experimental and Clinical Medicine, 2021
Kannan Vaidyanathan, Sandhya Gopalakrishnan
Lathosterolosis and Smith-Lemli-Opitz syndrome (SLOS) are congenital disorders of cholesterol synthesis which occur due to mutations in lathosterol 5-desaturase (SC5D) and7-dehydrocholesterol reductase (DHCR7) respectively. Proteomic analysis showed alterations in multiple pathways like mevalonatemetabolism, oxidative stress, apoptosis, protein biosynthesis, glycolysis, and intracellular trafficking [60].
Phytosteroids and Related Compounds
Published in Amritpal Singh Saroya, Contemporary Phytomedicines, 2017
Lathosterol, ergosterol, stigmasterol, 24-ethylcholesta-5,7,22-trienol, stigmasta- 7,24(24(1))-dien-3p-ol, and cholesterol have been reported. Sterol extract derived from alga Schizochytrium sp. possesses the same cholesterol-lowering activity as P-sitosterol (Chen et al. 2014).
Role of Micronutrients in Prevention of Coronary Artery Disease and Improvement of the Standard Therapy
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
In the HDL Atherosclerosis Treatment Study (HATS), the effects of the dietary antioxidants in combination with cholesterol-lowering drugs on stenosis and HDL-cholesterol were evaluated in CAD patients with low HDL.127,128 Dietary antioxidants vitamin C (1000 mg/day), vitamin E as D-α-tocopherol (800 IU/day), natural BC (25 mg/day, and selenium (100 µg/day) were given together with simvastatin-niacin in a subset of patients with low levels of HDL-cholesterol (Table 5.7). The results revealed that simvastatin-niacin-induced elevation of HDL-cholesterol was reduced by antioxidant supplements. The same group of investigators using the same formulation reported that a mixture of dietary antioxidants reduced the degree of proximal artery stenosis compared to placebo controls; however, in combination with simvastatin-niacin antioxidant supplementation was less effective than the simvastatin-niacin treatment alone in reducing the degree of stenosis. Because of the small sample size (40 patients per group) and unusually large variations in the results (200%–700% variation around the mean value),127 no conclusion regarding the value of antioxidants in combination with standard therapy in the management of stenosis can be drawn. This was further confirmed by the analysis of plasma levels of markers of cholesterol synthesis and absorption in the same study population. In this study, simvastatin-niacin treatment reduced plasma levels of desmosterol and lathosterol (markers of cholesterol synthesis) by 46% and 36%, respectively, whereas simvastatin-niacin plus antioxidant reduced each of them by 37% and 31%, respectively, suggesting no significant difference between two groups. Similarly, simvastatin-niacin treatment increased plasma levels of campesterol and beta-sitosterol (markers of cholesterol absorption) by 70% and 59%, respectively; whereas, simvastatin-niacin plus antioxidant increased each of them by 54% and 46%, respectively, suggesting no significant difference between two groups.129 Nevertheless, the authors concluded that mean changes in percent stenosis was positively associated with a percent change in the lathosterol level and negatively associated with a percent change in the β-sitosterol level. This conclusion does not appear to be consistent with their data on the markers of cholesterol synthesis and absorption. Thus, the conclusion that antioxidant supplementation can increase the level of stenosis in the group of CAD patients with low HDL receiving simvastatin-niacin therapy, may not be valid. These intervention studies with one or multiple dietary antioxidants in combination with cholesterol-lowering drugs, produced inconsistent results because other cardiac risk factors were not addressed, and appropriate preparation of antioxidants were not used in these studies.
Standardizing and increasing the utility of lipidomics: a look to the next decade
Published in Expert Review of Proteomics, 2020
Yuqin Wang, Eylan Yutuc, William J Griffiths
It is important to consider what is meant by identifying and subsequently quantifying a lipid. While the identity of a lipid can be determined by a combination of accurate mass measurement by MS and through NMR, very often providing the relevant stereochemistry, many lipidomic studies exploit MS with tandem MS (MS/MS) where the degree of structural identification is incomplete. MS when combined with chromatography can give accurate mass information and suggest chemical formulae for discreate lipids and if MS/MS or multistage fragmentation (MSn) is included information regarding the building blocks of a lipid may be forthcoming [16,17]. However, in the absence of more specialized adaptions e.g. keV collision-induced dissociation (CID) [18,19], ozoneolysis [20] or derivatization [21–23], determination of the position of double bonds can be difficult if not impossible, enantiomers cannot be differentiated in the absence of chiral chromatography and even diastereoisomers are difficult to differentiate in the absence of authentic standards [24]. Hence, it is important to define at what degree an identification is made in any lipidomic study [2,3,25]. While databases such as those provided by Lipid Maps are of huge value [26,27], their widespread use also provides a danger in that a measured m/z may be reported with a Lipid Maps ID in the absence of additional evidence, implying to the non-expert that the molecule defined by the Lipid Maps ID has been definitively identified when often this is not the case. There are many examples of this in the literature and it is a trap easy to fall into. To minimize miss communication and over reporting, a shorthand notation for lipid structures derived by MS has been proposed and has just been updated [2,3], adoption of this nomenclature by the community will minimize the number of misleading identifications made. It is important to be aware that even when all the chromatographic and MS data are considered it is still unlikely that an absolutely definitive identification will be made. To take an extreme example, while accurate mass measurement, GC retention time and electron – ionization (EI) fragmentation pattern will identify cholesterol, we need to use a chiral column to confirm we have the natural enantiomer not its synthetic equivalent. Of course, if the sample comes from a biological source it is legitimate to use our ‘biological intelligence’ and identify the lipid as cholesterol. We do, however, need to be careful in less obvious cases in the use of ‘biological intelligence’ and state clearly any assumptions that are made. By LC-MS/MS it would be very easy to confuse the isomers lathosterol and cholesterol and make the assumption that an appropriate peak, e.g. in a plasma sample, consisted exclusively of cholesterol. In all probability, this identification based on ‘biological intelligence’ would be correct, but not if the sample came from a child suffering from lathosterolosis, where the plasma concentration of lathosterol is elevated [28].