添加URL
分享
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov .
Get the latest research from NIH: https://www.nih.gov/coronavirus .
Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/ .
National Institutes of Health
National Library of Medicine
National Center for Biotechnology Information
NCBI homepage Show account info Choline is an essential nutrient for all cells because it plays a role in the synthesis of the membrane phospholipid components of the cell membranes, as a methyl-group donor in methionine metabolism as well as in the synthesis of the neurotransmitter acetylcholine. Choline deficiency affects the expression of genes involved in cell proliferation, differentiation, and apoptosis, and it has been associated with liver dysfunction and cancer. Abnormal choline transport and metabolism have been implicated in a number of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therefore, the study of choline transport and the characteristics of choline transporters are of central importance to understanding the mechanisms that underlie membrane integrity and cell signaling in such disorders. Kinetic studies with radiolabeled choline and inhibitors distinguish three systems for choline transport: (i) low-affinity facilitated diffusion, (ii) high-affinity, Na+-dependent transport, and (iii) intermediate-affinity, Na+-independent transport. It is only recently, however, that the proteins having transport characteristics of at least one of these systems have been identified. They include (i) polyspecific organic cation transporters (OCTs) with low affinity for choline, (ii) high-affinity choline transporters (CHT1s), and (iii) intermediate-affinity choline transporter-like (CTL1) proteins. CHT1 and CTL1 but not OCT transporters are selectively inhibited with hemicholinium-3 and essentially display characteristics of specialized transporters for targeted choline metabolism. CHT1 is abundant in neurons and almost exclusively supplies choline for acetyl-choline synthesis. The focus here is more on newly-discovered CTL1 choline transporters. They are expressed in different organisms and cell types, apparently not for the biosynthesis of acetylcholine but for the production of the most abundant metabolite of choline, the membrane lipid phosphatidylcholine. Inazu M, Yamada T, Kubota N, Yamanaka T. Inazu M, et al. Pharmacol Res. 2013 Oct;76:119-31. doi: 10.1016/j.phrs.2013.07.011. Epub 2013 Aug 13. Pharmacol Res. 2013. PMID: 23948665 Iwao B, Yara M, Hara N, Kawai Y, Yamanaka T, Nishihara H, Inoue T, Inazu M. Iwao B, et al. Neurochem Int. 2016 Feb;93:40-50. doi: 10.1016/j.neuint.2015.12.011. Epub 2015 Dec 31. Neurochem Int. 2016. PMID: 26746385 Lee NY, Choi HM, Kang YS. Lee NY, et al. Placenta. 2009 Apr;30(4):368-74. doi: 10.1016/j.placenta.2009.01.011. Epub 2009 Feb 26. Placenta. 2009. PMID: 19246089 Michel V, Bakovic M. Michel V, et al. Cent Nerv Syst Agents Med Chem. 2012 Jun;12(2):70-81. doi: 10.2174/187152412800792733. Cent Nerv Syst Agents Med Chem. 2012. PMID: 22483272 Review. Inazu M. Inazu M. Biopharm Drug Dispos. 2014 Nov;35(8):431-49. doi: 10.1002/bdd.1892. Epub 2014 Feb 27. Biopharm Drug Dispos. 2014. PMID: 24532461 Review. Jiang Q, Xu H, Yan J, Xu Q, Zheng Y, Li C, Zhao L, Gao H, Zheng H. Jiang Q, et al. Comput Struct Biotechnol J. 2020 Jul 31;18:2063-2074. doi: 10.1016/j.csbj.2020.07.019. eCollection 2020. Comput Struct Biotechnol J. 2020. PMID: 32802278 Free PMC article. Watanabe S, Nishijima N, Hirai K, Shibata K, Hase A, Yamanaka T, Inazu M. Watanabe S, et al. Pharmaceuticals (Basel). 2020 May 25;13(5):104. doi: 10.3390/ph13050104. Pharmaceuticals (Basel). 2020. PMID: 32466342 Free PMC article. McCann MR, McHugh CE, Kirby M, Jennaro TS, Jones AE, Stringer KA, Puskarich MA. McCann MR, et al. Metabolites. 2020 Apr 2;10(4):139. doi: 10.3390/metabo10040139. Metabolites. 2020. PMID: 32252461 Free PMC article. Maor-Landaw K, van Oppen MJH, McFadden GI. Maor-Landaw K, et al. Ecol Evol. 2019 Dec 12;10(1):451-466. doi: 10.1002/ece3.5910. eCollection 2020 Jan. Ecol Evol. 2019. PMID: 31993121 Free PMC article. Ishikawa T, Suwanai H, Shikuma J, Suzuki R, Yamanaka T, Odawara M, Inazu M. Ishikawa T, et al. Mol Med Rep. 2020 Feb;21(2):777-785. doi: 10.3892/mmr.2019.10894. Epub 2019 Dec 18. Mol Med Rep. 2020. PMID: 31974614 Free PMC article.