The Endogenous and Exogenous Substrate Spectrum of the Human Organic Cation Transporter OCT1 – a Comprehensive Characterization [thesis]

Jensen Ole
relevant fashion. Together, these findings may contribute to a gradually improving understanding of OCT1 functionality and biomedical relevance. the organic cation transporters from the SLC22 family (OCT1, OCT2, OCT3, OCTN1, OCTN2) and two multidrug and toxin extrusion proteins MATE1 (SLC47A1) and MATE2-K (SLC47A2) shows the amino acid sequence identity from pairwise comparisons in percent (left). The phylogenetic tree indicates evolutionary distances of these transporters (right). Amino acid
more » ... quences were analyzed by "Multiple Sequence Comparison by Log-Expectation" (MUSCLE) provided by the European Bioinformatics Institute, Hinxton (, and the phylogenetic tree was created from resulting data via the "Interactive Tree Of Life" (iTOL) online tool version 6 ( The substrate translocation by OCT1 has been described with the alternating access model (Koepsell 2011; Volk et al. 2009 ). The substrate binds to the transporter in its outward-open conformation and induces subsequent changes in protein conformation (Figure 4 ). In a non-ATPdependent manner ('facilitated diffusion'), the protein changes to the outward-occluded and inward-occluded state, in which the substrate is trapped inside the transporter, before it gets released from the transport protein in its inward-open state (Abramson et al. 2003; Koepsell 2015; Koepsell und Keller 2016). This process of facilitative diffusion depends on substrate concentration and membrane potential (Egenberger et al. 2012) . In contrast to antiporters, such as OCTN1 and OCTN2, transport by OCT1 is electrogenic, meaning charged molecules (cations) are transported across the cell membrane without compensation (Busch et al. 1996) . It was shown that OCT1 and other OCTs as well are able to facilitate not only uptake but also efflux of cations
doi:10.53846/goediss-8743 fatcat:m6rxk6gam5bbrcfnxx7uxnf6kq