China
Africa
Explore chapters and articles related to this topic
Natural Polyketides to Prevent Cardiovascular Disease
Published in Catherina Caballero-George, Natural Products and Cardiovascular Health, 2018
Additionally, there are pleiotropic effects that the inhibition of the mevalonate pathway may incur as a result of this pathway’s role in the production of a number of key isoprenoid intermediaries. The effect is due to the role that prenylation, the addition of hydrophobic molecules to a protein, plays in protein trafficking and cellular signaling by facilitating protein-membrane interactions. First, farnesyl pyrophosphate signals protein transport to the lumen of the endoplasmic reticulum for further modification and is implicated in interactions involving Ras family proteins. Second, geranylgeranyl pyrophosphate plays a role in the modulation of the RhoA, Rac and Cdc signaling pathways. These are integral GTPase proteins for cellular growth, proliferation and migration that are employed ubiquitously across normal cell types and are often the subject of mutation in tumorigenic cells (Liao and Laufs, 2005).
Vitamin E, α-Tocopherol
Published in Ruth G. Alscher, John L. Hess, Antioxidants in Higher Plants, 2017
Vitamin Ε belongs to a family of antioxidants that includes four methylated tocols, substituted with a phytyl chain, and the analogous tocotrienols, substituted with a geranylgeranyl chain (Figure l).2,14 Of the tocopherols, vitamin E, is the major constituent and contains the fully substituted benzoquinone ring, and is identified as 5,7,8-trimethyl tocol. The β-tocopherol (5,8-dimethyl tocol) and γ-tocopherol (7,8-dimethyl tocol) may exist as intermediates in the synthesis of vitamin Ε from the common precursor, δ-tocopherol (8-methyl tocol) (Figure 3). Although one might interconnect the pathways for the biosynthesis of these two classes of antioxidants,20 it is likely that there are similar but distinct methylation and cyclization steps for the synthesis of the tocols and the tocotrienols. Their synthesis may depend on both the site of synthesis and the availability of either phytyl pyrophosphate or geranylgeranyl pyrophosphate. The committed step for tocopherol biosynthesis is catalyzed by homogentisate decarboxylase phytyltrans-ferase.21 It is this cyclization step that forms the physiologically active d-isomer of the tocochromanols.
Lipid Subfraction Testing
Published in Stephen T. Sinatra, Mark C. Houston, Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
Coenzyme Q10 administration has been historically helpful in some patients who develop symptoms associated with statin use, but I have found minimal success with the addition of coenzyme Q10 allowing patients to then tolerate those statins to which they had previously been intolerant. Experiments have suggested that providing geranylgeranyl pyrophosphate (see Figure 4.2) could potentially reverse side effects of the statins but unblocking the decreased prenylation pathways would probably also reverse the beneficial anti-inflammatory element behind statin use. A coenzyme Q10 in statin myopathy study25 was begun in 2013. In this study, the treatment arm receives 600 mg of Coenzyme Q10 daily, attempting to ensure an adequate tissue dose of coenzyme Q10 is given.
Bone targeted new zoledronate derivative: design, synthesis, 99mTc-coupling, in-silico study and preclinical evaluation for promising osteosarcoma therapy
Published in International Journal of Radiation Biology, 2022
Hend Fayez, Adli Abdallah Selim
All the molecular modeling studies were carried out using Molecular Operating Environment (MOE, 2019.0102) software. All minimizations were performed with MOE until an RMSD gradient of 0.1 kcal·mol−1Å−1 with MMFF94x force field and the partial charges were automatically calculated. The X-ray crystallographic structure of human geranylgeranyl pyrophosphate synthase (GGPPS) co-crystalized with zoledronic acid (PDB ID: 6G31) was downloaded from the protein data bank (https://www.rcsb.org/structure/6G31). For each co-crystallized enzyme, water molecules and ligands which are not involved in the binding were removed; the protein was prepared for the docking study using Protonate 3D protocol in MOE with default options. The co-crystalized ligand was used to define the binding site for docking. Triangle Matcher placement method and London dG scoring function were used for docking.
Catechin regulates miR-182/GGPPS1 signaling pathway and inhibits LPS-induced acute lung injury in mice
Published in Immunopharmacology and Immunotoxicology, 2022
Yong Zhao, Hao Zheng, Shengnan Yang, Xiaoqing Zhang, Weigang Dong, Yu Shi, Yuechuan Li, Jing Feng
As a critical enzyme for synthesis of geranylgeranyl pyrophosphate synthase (GGPP), GGPPS1 is widely expressed in various tissues such as lung [5], liver [6] and testis [7]. As reported, GGPPS1 enhances Ras prenylation and exacerbates insulin resistance through MAPK pathway in the pathogenesis of type 2 diabetes [8]. Moreover, GGPPS1 is up-regulated in the mice lung after exposure to cigarette smoke, which closely links to ALI/ARDS [9]. Notably, specific knockout of GGPPS1 in lung can improve LPS-induced ALI predominantly by suppressing the activation of NLRP3 inflammasome. However, the mechanism underlying the inhibition of GGPPS1 on the protection against ALI remains largely unexplored.
The safety profile of denosumab in oncology beyond the safety of denosumab as an anti-osteoporotic agent: still more to learn
Published in Expert Opinion on Drug Safety, 2021
Maria V. Deligiorgi, Dimitrios T. Trafalis
Finally, genetic mutations in the enzyme geranylgeranyl pyrophosphate synthase ‒a key-enzyme of the mevalonate pathway‒ have been reported to predispose to AFFs related to long-term BP therapy [110]. The aforementioned mechanism merit further evaluation in the setting of denosumab-related AFFs.