Cellular transport and selective accumulation of potentially toxic xenobiotics
7 important questions on Cellular transport and selective accumulation of potentially toxic xenobiotics
What are the 4 basic mechanisms that are implicated in transmembrane transport of xenobiotics?
2) Facillitated diffusion: membrane proteins that transport the xenobiotics by specific binding followed by a conformational change and subsequent release of the compound. Driven by chemical or electrochemical potential. There can be saturation, inhibition, high selectivity, temperature dependence. Often this kind of transport is coupled and driven by cotransport.
3) Active transport: transport against a concentration gradient.
4) endocytosis: for large molecules or particles. ATP and Calcium dependent.
What are the mechanisms behind hepatocyte-selective uptakeof alpha-amanitin?
- The normal function of this transporter is to extract bile salts from the ciruclation.
- Facilitated diffusion.
- probably the NCTP (functions undirectly) transporter in rats, in human liver, it is the OATP1B3.
- When it is in the hepatocyte it can damage RNA polymerase II.
What are the mechanisms behind paraquat injury in alveolar cells?
- accumulates in the lung and it retaines there even if blood levels decrease.
- accumulation occurs in an energy dependent manner.
- accumulation features saturability
- Probably the polyamine transport is the reason for paraquat uptake.
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Why polyamines and paraquat?
What is the difference in function between alveolar 1 and 2 cells?
2: surfactant secretion, active transport of water and ions and epithelial regeneration. The role of surfactant is to form a thin layer that covers the epithelial cells. This decreases the surface tension and also acts as a defense against noxious agents.
What are the mechanisms behind benoxaprofen induced cholestasis?
3 factors
1) benox. acyl glucuronide is poorly water soluble and might therefore precipitate in the biliary tree as a function of its increasing concentration.
2) alkaline pH of bile, therefore the acyl glucuronide is more likely to hydrolyze.
3) It can form covalent adduct to canalicular proteins.
4) vectorial transport of benox by MRP2 into the bile.
What are the mechanisms of protection from methoxychlor toxicity in the testis?
- In the testis MRP1 is abundantly expressed especially at the basolateral side of the sertolicells and Leydigcells.
- If MRP1 is affected this could result in a decreased amount of spermatocytes for example.
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