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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].
Implication of Mitochondrial Coenzyme Q10 (Ubiquinone) in Alzheimer’s Disease *
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Sayantan Maitra, Dibyendu Dutta
The adverse effects of two classes of drugs, viz., anthracyclines and statins, are well documented by both preclinical and clinical studies. Although anthracyclines (doxorubicin, daunorubicin) are the excellent chemotherapeutic drugs, they also induce cardiotoxicity. These groups of drugs cause an irreversible damage to myocardial mitochondria and can be prevented by a concurrent administration of CoQ10 during cancer chemotherapy [75]. Antihyperlipidemic drugs known as statins (HMG-CoA reductase inhibitors) such as lovastatin and pravastatin inhibit the cholesterol synthesis. These drugs also impair the endogenous synthesis of CoQ10 resulting in its depletion. These drugs lead to myopathy in some cases, and life-threatening rhabdomyolysis in extreme cases, and these adverse effects can be prevented by CoQ10 supplementation [76,77]. Beta-blockers such as propranolol and metoprolol have shown to decrease the endogenous serum CoQ10 level by inhibiting CoQ10-dependent enzymes [78]. Because of its structural resemblance to vitamin K, it has been suggested that CoQ10 may counteract the anticoagulant activity of warfarin [79,80].
Disorders in tHemostasis System and Changes in the Rheological Properties of the Blood in Ischemic Heart Disease and Diabetes Mellitus Patients
Published in E.I. Sokolov, Obesity and Diabetes Mellitus, 2020
An important role in the development of angiopathies in DM is played by hyperlipidemia and dysproteinemia [380, 466, 525, 515, 611]. The disorders in fat metabolism in DM can be explained pathophysiologically by lowering of the activity of the pentosophosphate cycle — the main path of glucose transformation. Suppression of the cycle lowers the reduction of NADP. This inhibits lipogenesis with the simultaneous increase in cholesterol synthesis.
Mechanisms of dihydromyricetin against hepatocellular carcinoma elucidated by network pharmacology combined with experimental validation
Published in Pharmaceutical Biology, 2023
Shuo Zhang, Ya-Ning Shi, Jia Gu, Peng He, Qi-Di Ai, Xu-Dong Zhou, Wei Wang, Li Qin
HCC is a type of cancer accompanied by dyshomeostasis of the internal environment, especially in lipid metabolism disorder (Luo et al. 2020; Li et al. 2022). There is a strong correlation between cholesterol and HCC. Generally, cholesterol is de novo synthesized, catabolized, and reverse-transported in the liver (Luo et al. 2020). Most of the cellular cholesterol is located on the plasma membrane, where it forms lipid rafts with sphingolipids and other proteins, serving as a platform for receptor trafficking and signal transduction that could promote the occurrence and development of cancers (Lingwood and Simons 2010; Greenlee et al. 2021). As early as 1990, studies have shown that cholesterol synthesis was enhanced in HCC (Kawata et al. 1990). Emerging evidence found that cholesterol affected HCC progression in various aspects. For example, increased cholesterol biosynthesis drives drug resistance of HCC, self-renewal of CSCs in HCC, and tumorigenesis (Wang et al. 2021; Mok et al. 2022). In addition, cholesterol accumulation reduces the antitumor immune response mediated by natural killer T cells in HCC (Tang et al. 2022). Moreover, cholesterol promotes the progression from non-alcoholic fatty liver disease to HCC by activating mTORC1 (Liu et al. 2022). Notably, cholesterol-lowering drugs are associated with a reduction in cancer-related mortality (Nielsen et al. 2012; Cardwell et al. 2014). Thus, lowering cholesterol might be an effective way to cancer prevention.
Inflammasomes: a preclinical assessment of targeting in atherosclerosis
Published in Expert Opinion on Therapeutic Targets, 2020
Jeremiah Stitham, Astrid Rodriguez-Velez, Xiangyu Zhang, Se-Jin Jeong, Babak Razani
Arglabin is a plant-derived terpenoid compound that acts as a farnesyl transferase inhibitor most notably leading to the activation of RAS proto-oncogene, pivotal in human tumors. Arglabin has also shown to reduce inflammation induced by atherosclerosis through a number of unexplained mechanisms. Arglabin also decreased plasma total cholesterol and triglycerides. The inhibition of cholesterol synthesis may occur by way of blocking enzymes downstream of 3β-hydroxy-3β-methyl-glutaryl coenzyme A reductase (HMGR), such as farnesyl diphosphate farnesyl-transferase, which catalyzes the first committed step in de novo cholesterol biosynthesis [210]. As such, Arglabin be a potentially good candidate to treat hypercholesterolemia and reduce atherosclerotic plaque size in addition to its inhibition of the NLRP3 inflammasome activity. In an ApoE−/− atherosclerotic mouse model fed with a high-fat diet, Arglabin effectively inhibited the NLRP3 inflammasome activity and significantly reduced the production of pro-inflammatory cytokines IL-1β, IL-18, and IL-1α in vitro and in vivo [210]. Arglabin activated autophagy as evidenced by the increase in LC3-II protein, which is a central protein in the autophagy pathway. Thus, in an ApoE2.Ki mouse model, Arglabin seemingly has the dual distinction of reducing inflammation via NLRP3 inflammasome inhibition as well as normalizing plasma cholesterol and triglyceride levels.
Associations between ketone bodies and fasting plasma glucose in individuals with post-pancreatitis prediabetes
Published in Archives of Physiology and Biochemistry, 2020
Sakina H. Bharmal, Sayali A. Pendharkar, Ruma G. Singh, David Cameron-Smith, Maxim S. Petrov
Insulin has a stimulatory effect on cholesterol synthesis (Lakshmanan et al.1973). Evidence from pre-clinical and clinical studies has demonstrated that mevalonate (a biomarker of cholesterol synthesis) is inversely associated with BHB (Parker et al.1984, Kemper et al.2015). In the present study, BHB changed by −0.55 mmol/L (p = .008) with every unit change in LDL:HDL cholesterol, in individuals with PPP. This inverse association between BHB and LDL:HDL cholesterol can be explained by the insulin’s regulation of the cholesterol biosynthetic pathway. Cholesterol is synthesised from acetyl-CoA. The enzyme HMG-CoA synthase catalyses the conversion of acetyl-CoA to HMG-CoA, which is the intermediary step in both ketogenesis and cholesterol synthesis (Liscurn 2002). There are two forms of the HMG-CoA enzyme, of which one is involved in ketogenesis whereas the other catalyses the conversion of HMG-CoA to mevalonate (Liscurn 2002). Given that the initial steps of ketone and cholesterol synthesis are identical, it is conceivable that, in PPP, high plasma levels of insulin modulate the cAMP-dependent signal transduction pathway (Bruss 1997, Omar et al.2009) to favour synthesis of mevalonate and subsequently cholesterol.