Movement across membranes Flashcards
What does membrane permeability do?
- Maintains the internal environment
- Selectively permeable
- Gases diffuse very easily
What might impermeable substances need to transport across the membrane?
- Transport proteins
- Energy
- E.g. ions will need help
What type of channels are there within the membrane?
- Channels
- Narrow aqueous pore
- Selective (size, charge)
- Passive
- May be gated (voltage or ligand)
- Usually ions (e.g. Na+) or water (aquaporins)
What type of carriers are there within the membrane?
- 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
What are the three main forces that drive substances in/out of cells?
- Chemical
- Electrical
- Electrochemical
What are driving forces 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
What is the chemical driving force?
- Based on concentration differences across the membrane
- All substances have a concentration gradient
- Force directly proportional to the concentration gradient
What is the electrical driving force?
- 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
What is the electrochemical driving force?
- 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+
What are the two types of membrane transport?
Passive:
- simple diffusion
- facilitated diffusion
Active:
- Primary
- secondary (uses movement of an ion that is being actively tansported)
What is passive transport?
- 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
Give an example of passive transport?
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
What can happen if we have too much glucose during pregnancy?
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
What is GLUT 1 Deficiency syndrome?
- 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
What is active transport?
- Requires an input of energy
- Substance moves against its gradient (low to high)
Two types: - Primary
- Secondary
What is primary active transport?
- 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
what happens when primary active transport goes wrong?
- 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
What is secondary active transport?
- 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)
What is an example of secondary active transport?
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
What happens when secondary active transport goes wrong?
- 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
What is cellular signalling?
Communication between cells takes place via signalling molecules e.g. hormones, neurotransmitters and growth factors
What are some signalling molecules?
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
What happens when cellular signalling goes wrong?
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
What is endocytosis?
Large molecules require different methods of transport:
1. Endocytosis:
Transport into a cell
E.g. Phagocytosis, Pinocytosis, Receptor-mediated endocytosis
What is exocytosis?
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)
What is Cystic Fibrosis?
- 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
What drugs target membrane trasnporters?
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
