Movement across membranes Flashcards

1
Q

What does membrane permeability do?

A
  • Maintains the internal environment
  • Selectively permeable
  • Gases diffuse very easily
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2
Q

What might impermeable substances need to transport across the membrane?

A
  • Transport proteins
  • Energy
  • E.g. ions will need help
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3
Q

What type of channels are there within the membrane?

A
  • Channels
  • Narrow aqueous pore
  • Selective (size, charge)
  • Passive
  • May be gated (voltage or ligand)
  • Usually ions (e.g. Na+) or water (aquaporins)
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4
Q

What type of carriers are there within the membrane?

A
  • Specific binding site
    -Carrier undergoes a conformational change
    Different types:
  • Uniport – single substance
  • Symport – two substances in the same direction
  • Antiport – two substances in the opposite direction
    Active (pumps) or passive
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5
Q

What are the three main forces that drive substances in/out of cells?

A
  • Chemical
  • Electrical
  • Electrochemical
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6
Q

What are driving forces based on?

A

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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7
Q

What is the chemical driving force?

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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8
Q

What is the 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+ will set up a small potential difference across the membrane
  • Force depends on size of membrane potential and charge of the ion
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9
Q

What is the electrochemical driving force?

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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10
Q

What are the two types of membrane transport?

A

Passive:
- simple diffusion
- facilitated diffusion
Active:
- Primary
- secondary (uses movement of an ion that is being actively tansported)

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11
Q

What is 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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12
Q

Give an example of passive transport?

A

GLUT4 carrier protein:
- Expressed in skeletal muscle and adipose tissue
- Glucose uptake by facilitated diffusion
- Expression up-regulated by insulin
So in the absence of insulin, glucose can not enter the cell.
If insulin is present it signals the cell to insert GLUT 4 transporters into the membrane, allowing glucose to enter the cell

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13
Q

What can happen if we have too much glucose during pregnancy?

A

Principal fetal nutrient
- Fetal gluconeogenic enzymes inactivated
- Low arterial PO2
From maternal circulation
Transports 0.6 mmol/min/g placental tissue (~0.11g glc/min/g)
Carrier system saturates at ~20 mmol/L (Glut-1; ~3.6g/L)
- Fetal glucose levels directly related to mother’s
- No mechanism to limit uptake below saturation point
- Excess glucose can cause significant fetal harm

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14
Q

What is GLUT 1 Deficiency syndrome?

A
  • 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 and there is 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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15
Q

What is active transport?

A
  • Requires an input of energy
  • Substance moves against its gradient (low to high)
    Two types:
  • Primary
  • Secondary
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16
Q

What is primary active transport?

A
  • Directly uses a source of energy, commonly ATP
  • Common example is Na+/K+-ATPase:
  • Pumps 3 Na+ out of the cell, 2 K+ into the cell
  • Utilises the hydrolysis of ATP to ADP + Pi
17
Q

what happens 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
  • Rare disorder
  • Mutations in ATP7B gene
  • Results in deposition of copper in the liver and other tissues e.g. brain, eyes
  • Symptoms include liver disease, tremor, Kayser-Fleischer rings
18
Q

What is secondary active transport?

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)
19
Q

What is an example of secondary active transport?

A

Example is the Na+/glucose co-transporter 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

20
Q

What happens 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
21
Q

What is cellular signalling?

A

Communication between cells takes place via signalling molecules e.g. hormones, neurotransmitters and growth factors

22
Q

What are some signalling molecules?

A

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

23
Q

What happens 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 Gas subunit (Intra-cellular action)
- Results in increased second messenger (cAMP) levels
- This stimulates several transporters in the cell m- 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

24
Q

What is endocytosis?

A

Large molecules require different methods of transport:
1. Endocytosis:
Transport into a cell
E.g. Phagocytosis, Pinocytosis, Receptor-mediated endocytosis

25
Q

What is exocytosis?

A

Large molecules require different methods of transport:
2. Exocytosis:
Transport out of a cell
E.g. Constitutive secretion (e.g. antibodies) + Regulated secretion (synaptic transfer. Depolarisation at a nerve terminal where a neurotransmitter is released)

26
Q

What is Cystic Fibrosis?

A
  • Common hereditary disorder (1 in 25 people are carriers)
    Mutation in CFTR protein:
  • Chloride channel
  • Found in many tissues e.g. Gut, pancreas, lungs and skin
  • “secretory epithelium”
    -Abnormal function results in sticky, viscous mucus
  • No osmotic drag
27
Q

What drugs target membrane trasnporters?

A

Cardiac glycosides e.g. digoxin:
- Act on Na+/K+-ATPase in cardiac muscle cells
- Indirect action to increase intra-cellular [Ca2+]

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