Membrane Transportation

Membrane Transportation

Which ABC transporter plays a role in cholesterol and phospholipid transport in hepatocytes?

Row labeled Q30 appears truncated but query addresses which ABC transporter handles cholesterol and phospholipid transport in hepatocytes. In canalicular membrane ABCB4 MDR3 is established phosphatidylcholine floppase essential for biliary phospholipid secretion, pairing with bile salt export via ABCB11 and cholesterol export via ABCG5/G8. Its ATP-driven flipping of phosphatidylcholine to outer leaflet allows bile acids to extract lipid into mixed micelles that solubilize cholesterol and buffer bile acid detergent toxicity. At sinusoidal membrane, ABCA1 effluxes cholesterol and phospholipid to

Ref: Borst et al., Annu Rev Biochem 2000, ABC transporters in lipid transport; Alberts, Chapter 11.

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Membrane Transportation

Which ABC transporter plays a role in cholesterol and phospholipid transport in hepatocytes?

Cholesterol and phospholipid homeostasis in hepatocytes involves coordinated action of several ABC transporters at canalicular membrane. ABCB4 MDR3 flips phosphatidylcholine from inner to outer leaflet making it available for bile salt extraction forming mixed micelles that protect biliary epithelium and solubilize cholesterol exported by ABCG5/G8 heterodimer. ABCB1 MDR1 primarily exports hydrophobic xenobiotics and drugs, not bulk phospholipid for bile formation, though it can translocate short-chain lipids in vitro. ABCA1, not listed among options but relevant, mediates phospholipid and chol

Ref: Oude Elferink & Paulusma 2007, Hepatic lipid transporters; Nicolaou et al., J Hepatol 2012.

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Membrane Transportation

What is the primary function of Na+/K+ ATPase in maintaining secondary active transport?

Primary role of Na+/K+ ATPase in context of secondary active transport is generation and maintenance of electrochemical sodium gradient that powers numerous symporters and antiporters. By pumping three Na+ outward and two K+ inward per ATP hydrolyzed, it creates chemical gradient low intracellular Na+ and electrical gradient interior negative near minus 70 mV. Combined sodium motive force represents stored free energy. Solute carrier families SLC5 SGLT, SLC6 neurotransmitter transporters, SLC38 amino acid transporters, SLC9 NHE and SLC8 NCX exploit this force allowing Na+ to move downhill whil

Ref: Alberts et al., 7th ed., Chapter 11, Na+/K+ pump and secondary transport coupling.

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Membrane Transportation

Which ion transporter is defective in cystic fibrosis?

Cystic fibrosis is monogenic disease caused by dysfunction of chloride and bicarbonate channel CFTR, ABCC7, not by Na+/K+ ATPase primary gradient generator nor by V-type proton pump acidifying organelles nor by ABCB1 drug efflux pump. CFTR localized apically in respiratory epithelium, pancreatic ductules, sweat duct, intestinal crypts and male reproductive tract mediates cAMP-activated Cl- secretion driving fluid movement and maintaining airway surface liquid hydration and mucus viscosity. Loss-of-function reduces chloride and bicarbonate secretion, leads to thickened secretions, obstructive l

Ref: Riordan et al., Annu Rev Biochem 2008, CFTR and cystic fibrosis; Davies et al., Science 2023.

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Membrane Transportation

Which of the following describes V-class ATPases?

V-class ATPases, vacuolar type H+-ATPases, are multi-protein rotary pumps distinct from glucose carriers SGLT or drug exporters ABCB1. They hydrolyze ATP in cytosolic V1 sector comprising A3B3 catalytic hexamer and use released energy to rotate central stalk and translocate protons through membrane-embedded Vo sector containing c-ring proteolipids and subunit a. Cellular localization includes lysosomes, endosomes, trans-Golgi network, synaptic vesicles, secretory granules, osteoclast ruffled border and kidney intercalated cell apical membrane. By acidifying compartments to pH 4.5-5.5 they crea

Ref: Forgac, Nat Rev Mol Cell Biol 2007, V-ATPase function; Nelson & Harvey, Annu Rev Cell Biol 1999.

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Membrane Transportation

The ABC transporter CFTR is unique because:

CFTR ABCC7 stands as atypical member of ABC superfamily because evolution transformed an active exporter scaffold into ATP-gated ion channel. Typical ABC exporters use ATP binding and hydrolysis to drive large TMD movements translocating substrate uphill. In CFTR, transmembrane domains create chloride-selective pore allowing passive flow down electrochemical gradient when open, while nucleotide-binding domains still bind ATP and regulate gating rather than transport solute stoichiometrically. Two ATP sites: NBD1 non-canonical hydrolyzes slowly, NBD2 drives channel closure upon hydrolysis. Addi

Ref: Gadsby et al., Nature 2006, Unique CFTR channel mechanism; Hwang & Sheppard, 2009.

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Membrane Transportation

Which of the following describes SGLT2?

Sodium glucose cotransporters SGLT1 SLC5A1 and SGLT2 SLC5A2 are secondary active members using sodium gradient but differ in location, affinity and role. SGLT1 expressed predominantly in apical brush border of small intestine enterocytes and early kidney proximal tubule S3 is high-affinity low-capacity with 2 Na+ to 1 glucose stoichiometry handling dietary glucose and galactose absorption and some glucose reabsorption. SGLT2 localized exclusively in S1 and S2 segments of proximal tubule is low-affinity high-capacity with 1 Na+ to 1 glucose stoichiometry accounting for roughly 90 percent renal

Ref: Wright et al., Physiol Rev 2011, SGLT1 vs SGLT2 distribution and physiology.

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Membrane Transportation

Which transporter regulates bile phospholipid transport in hepatocytes?

Phosphatidylcholine supply to bile is governed by canalicular ABC transporter ABCB4, also known as multidrug resistance protein 2 or 3 in rodents and humans. This ATP-driven floppase actively translocates endogenous phosphatidylcholine from inner cytoplasmic leaflet to outer exoplasmic leaflet of hepatocyte canalicular membrane. Bile salts secreted via ABCB11 then extract phospholipid into bile forming mixed micelles that solubilize cholesterol and shield ductal epithelium from detergent toxicity of bile acids. ABCB1 MDR1 contributes to hydrophobic xenobiotic efflux but does not move bulk phos

Ref: Oude Elferink & Paulusma, Pflugers Arch 2007, ABCB4 phosphatidylcholine transport.

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Membrane Transportation

In secondary active transport, lactose permease in E. coli utilizes:

Secondary active lactose permease LacY does not itself hydrolyze ATP nor perform direct phosphorylation of sugar substrate like phosphotransferase systems that import glucose as glucose-6-phosphate. Instead energy source is electrochemical proton gradient across E. coli inner membrane established by respiratory chain proton pumping. Lactose entry is strictly coupled to downhill H+ flow: one proton symported per lactose disaccharide. Experimental evidence shows that abolishing proton motive force with uncouplers carbonyl cyanide m-chlorophenyl hydrazone, nigericin, or by inhibiting respiration

Ref: Kaback et al., J Gen Physiol 2008, Proton coupling LacY; Poolman et al., Mol Microbiol 2004.

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Membrane Transportation

Which ABC transporter is associated with multidrug resistance in cancer?

Cancer multidrug efflux is dominated not by CFTR or P-type ATPases but by ABC transporters that expel amphipathic chemotherapeutics from cytoplasm. ABCB1 P-glycoprotein MDR1 is best studied, overexpressed in colonic, renal, adrenocortical carcinomas and after chemotherapy induction in leukemia, lymphoma and breast cancer. Its polyspecific hydrophobic binding chamber accommodates doxorubicin, daunorubicin, vinblastine, vincristine, paclitaxel and etoposide causing cross-resistance. ABCC1 MRP1 exports glutathione conjugates of drugs, ABCG2 BCRP expels mitoxantrone and topotecan. Expression corre

Ref: Gottesman et al., Annu Rev Med 2002, MDR in cancer; Szakacs et al., Nat Rev Drug Discov 2006.

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Membrane Transportation

The ABC transporter in plants responsible for detoxification of xenobiotics is found in:

Plants lack animal Na+/K+ gradient but generate proton motive force via plasma membrane P-type H+-ATPase and vacuolar V-type H+-ATPase and pyrophosphatase, driving uptake and compartmentalization of metabolites. Detoxification of xenobiotics, herbicides, and endogenous secondary metabolites employs ATP-binding cassette transporters localized predominantly in vacuolar membrane tonoplast and plasma membrane. Vacuolar ABCC members often called MRP-like transport glutathione S-conjugates, phytochelatin heavy metal complexes, and glucuronide conjugates into vacuole for sequestration, reducing cytos

Ref: Martinoia et al., Planta 2002, Vacuolar transporters; Kang et al., PNAS 2011, ABC in detox.

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Membrane Transportation

Which of the following is not a characteristic of secondary active transport?

Secondary active transport refers to movement of solute against its concentration gradient energized indirectly by ion electrochemical gradient established by primary active pumps, not by direct ATP binding and hydrolysis at transport protein itself. Hallmarks include dependence on Na+/K+ ATPase or H+-ATPase to maintain Na+ or H+ motive force, inhibition by collapse of gradient with ionophores or ouabain, and involvement of symport or antiport mechanisms where downhill flow of driving ion drags substrate uphill. Protein operates by alternating access rocker-switch mechanism without Walker A AT

Ref: Alberts et al., 7th ed., Chapter 11, Distinction primary vs secondary active transport.

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