movement across membranes Flashcards

1
Q

channel proteins

A
  • Narrow aqueous pore
  • Selective: size, charge
  • Passive
  • May be gated (voltage or ligand)
  • Usually ions (e.g. Na+, K+) or water (aquaporins)
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2
Q

carrier proteins

A
  • Specific binding site
  • Carrier undergoes a conformational change
  • Different types: uniport- single substances, symport- two substances in the opposite direction
  • Antiport – two substances in the opposite direction
  • Active (pumps) or passive
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3
Q

driving forces

A
  • Three main forces that drive substances into/out of cells: chemical, electrical, electrochemical
  • Based on the presence of a gradient
  • Substances either move with the gradient (high to low) or can move against the gradient (low to high) with help
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4
Q

chemical driving forces

A
  • Based on concentration differences across the membrane
  • All substances have a concentration gradient
  • Force directly proportional to the concentration gradient
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5
Q

electrical driving force

A
  • Also known as membrane potential
  • Based on the distribution of charges across the membrane
  • Only charged substances e.g. Na+. K+
  • Force depends on size of membrane potential and charge of the ion
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6
Q

electrochemical driving forces

A
  • Combines the chemical and electrical forces
  • Net direction is equal to the sum of chemical and electrical forces
  • Only charged substances e.g. Na+, K+
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7
Q

passive transport

A
  • Does not require an input of energy
  • Substance moves down its gradient (high to low)
  • Two types: simple diffusion e.g. gases, facilitated diffusion – mediated by proteins (channel or carrier)
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8
Q

passive transport of glucose

A

• GLUT4 carrier protein:
• Expressed in skeletal muscle and adipose tissue
• Glucose uptake by facilitated diffusion
• Expression upregulated by insulin
When it goes wrong …
• GLUT1 present in many cells, including the brain, where it transports glucose across the blood-brain barrier via facilitative diffusion
• GLUT1 Deficiency Syndrome:
• Very rare disorder
• Mutations in gene that encodes GLUT1
• Less functional GLUT1 - reduces the amount of glucose available to brain cells
• Symptoms include seizures, microcephaly, developmental delay

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9
Q

active transport -primary

A

Active transport – primary
• Directly uses a source of energy, commonly ATP
• Common example is Na+/K+-ATPase:
• Pumps 3 Na+ out of cell, 2 K+ into the cell
• Utilises the hydrolysis of ATP to ADP + Pi

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10
Q

when primary active transport goes wrong

A

• ATP7B protein is a Cu2+-ATPase present in the liver that transports copper into bile
• Wilson’s disease
o Rare disorder
o Mutations in ATP7B gene
o Results in deposition of copper in the liver and other tissues e.g. brain, eyes
o Symptoms include liver disease, tremor, Kayser-Fleischer rings

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11
Q

active transport - secondary

A
  • Transport of a substance against its gradient COUPLED to the transport of an ion (usually Na+ or H+), which moves down its gradient
  • Uses energy from the generation of the ions electrochemical gradient (usually by primary active transport)
  • Example is the Na+/glucose cotransporter proteins (SGLT): Present in intestinal lumen and renal tubules. Transports glucose from low to high concentration
  • Na+/K+-ATPase generates a sodium gradient to enable co-transport of sodium and glucose
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12
Q

when secondary active transport goes wrong

A
  • SGLT1 transports glucose and galactose from the intestinal lumen
  • Glucose-Galactose Malabsorption: Very rare disorder, Mutations in SGLT1, less functional SGLT1 -inability to transport glucose and galactose, resulting in their malabsorption
  • Symptoms include severe, chronic diarrhoea, dehydration, failure to thrive
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13
Q

cellular signalling

A
  • Communication between cells takes place via signalling molecules e.g. hormones, neurotransmitters and growth factors
  • Signalling molecules bind to receptors: intracellular – e.g. steroid hormones, cell-surface – e.g. peptide hormones
  • Second messengers e.g. cAMP, IP3, DAG, Ca2+ - amplification
  • Affect gene expression in the nucleus either directly or through signalling cascades
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14
Q

when cellular signalling goes wrong

A
  • G proteins integral part of G-protein- coupled receptors on cell membrane surfaces
  • Cholera: Vibrio cholerae bacteria produce the cholera toxin. This crosses the cell membrane. Modifies a subunit of the G protein. Results in increased second messenger (cAMP) levels. This stimulates several transporters in the cell membrane of intestinal cells. Results in massive secretion of ions and water into the gut. Leads to severe diarrhoea and dehydration that can be fatal
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15
Q

endocytosis & exocytosis

A
  • Large molecules require different methods of transport
  • Endocytosis transport into cell
  • Exocytosis transports out of cell
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16
Q

cystic fibrosis

A
  • Common hereditary disorder (1 in 25 people are carriers)
  • Mutation in CFTR protein: chloride channel, found in many tissues e.g pancreas, lungs, skin, abnormal function results in sticky, viscous mucus
17
Q

examples of drugs which target membrane transporters

A
  • Cardiac glycosides e.g. digoxin (Act on Na+/K+-ATPase in cardiac muscle cells)
  • Proton pump inhibitors e.g. omeprazole (Act on H+/K+-ATPase in gastric parietal cells)
  • Loop diuretics e.g. furosemide (Act on NKCC2 cotransporter in thick ascending limb of loop of Henle)
  • Thiazide diuretics e.g. bendroflumethiazide (Act on NCC cotransporter in distal tubule )