The MDR1 (ABCB1) transporter is responsible for:
MDR1 officially ABCB1, also called P-glycoprotein P-gp, is a 1280 amino acid 170 kDa glycosylated plasma membrane exporter noted for conferring resistance to colchicine and doxorubicin in selection experiments. Tissue distribution includes apical brush border of small intestinal enterocytes limiting drug absorption, canalicular membrane of hepatocytes promoting biliary excretion, luminal membrane of proximal renal tubule mediating urinary elimination, endothelial cells of blood-brain barrier restricting central entry, and placental syncytiotrophoblast protecting fetus. Substrates are typically neutral or cationic amphipathic molecules of 300 to 2000 Da that partition into lipid bilayer such as paclitaxel, vincristine, etoposide, imatinib and cyclosporine. Transport cycle involves two ATP hydrolysis events: ATP binding closes NBD dimer, induces outward-facing TMD conformation collapsing high-affinity pocket and expelling substrate, then hydrolysis resets system. Genomic amplification and pregnane X receptor mediated induction after chemotherapy increase efflux, lowering cytosolic concentration and causing therapy failure requiring dose escalation and combination strategies. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.
Ref: Sharom, Pharmacogenomics 2008, P-glycoprotein; Alberts, 7th ed., Chapter 11 MDR transporters.