Transporters and Genomics

The apical localized sodium-dependent bile add transporter (ASBT) is expressed in the human duodenum and ileum and is barely detectable in colon [16]. ASBT transports bile adds such as glycodeoxycholate and chenodeoxycholic add (XX) [49, 50]. Few examples exist where the bile acid scaffold has been used as a promoiety for a prodrug approach. ASBT has micromolar affinities for the natural substrates, and the studies on ASBT are too few to make a general statement on the potential and role of this transporter in drug absorption [49, 50]. 

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Mitochondria are unique organelles in that they contain their own DNA (mtDNA), which, in addition to ribosomal RN A (rRNA) and transfer RN A (tRNA)-coding sequences, also encodes 13 polypeptides which are components of complexes I, III, IV, and V (Anderson et al., 1981). This fact has important implications for both the genetics and the etiology of the respiratory chain disorders. Since mtDNA is maternally-inherited, a defect of a respiratory complex due to a mtDNA deletion would be expected to show a pattern of maternal transmission. However the situation is complicated by the fact that the majority of the polypeptide subunits of complexes I, III, IV, and V, and all subunits of complex II, are encoded by nuclear DNA. A defect in a nuclear-coded subunit of one of the respiratory complexes would be expected to show classic Mendelian inheritance. A further complication exists in that it is now established that some respiratory chain disorders result from defects of communication between nuclear and mitochondrial genomes (Zeviani et al., 1989). Since many mitochondrial proteins are synthesized in the cytosol and require a sophisticated system of posttranslational processing for transport and assembly, it is apparent that a diversity of genetic errors is to be expected. 

Wu, X., et al. cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem. Biophys. Res. Commun. 1998, 246, 589-595. 

Konig, J., et al. Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide. J. Biol. Chem. 2000, 275, 23161-23168. 

Doege, H., et al. Activity and genomic organization of human glucose transporter 9 (GLUT9), a novel member of the family of sugar-transport facilitators predominantly expressed in brain and leucocytes. Biochem. J. 2000, 350, 771-776. 

Dean, M., Rzhetsky, A. and Allikmets, R. (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Research, 11, 1156-1166. 

Shin, J.-G. (2008) The effect of SLC01B1 15 on the disposition of pravastatin and pitavastatin is substrate dependent the contribution of transporting activity changes by SLC01B1 15. Pharmacogenetics and Genomics, 18 (5), 424 33. 

How complex can the proteome of hydrogenosomes in T. vaginalis be expected to be Trichomonad hydrogenosomes have lost many standard metabolic capacities of mitochondria like—and consequently most of the proteins involved in—the tricarboxylic cycle, membrane-bound electron transport and ATP-production (Muller 1993), or fatty acid synthesis (Beach et al. 1990). Because of the absence of a genome (Clemens and Johnson 2000) the complex machineries of DNA replication and repair, gene transcription and protein synthesis are also absent from these organelles. On the other hand, experimental evidence exists for only a small number of metabolic... 

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