Movement Across Membranes Flashcards
Membrane permeability
• Maintains the internal environment
•Selectively permeable
•For membrane transport, impermeable substances may need:
•Transport proteins
•Energy
Membrane proteins- channels
•Narrow aqueous pore
•Selective:
•Size
•Charge
•Passive
•May be gated (voltage or ligand)
•Usually ions (e.g. Na+, K+) or water (aquaporins)
Membrane proteins- Carriers
•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
Driving forces
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
Driving forces- Chemical
•Based on concentration differences across the membrane
•All substances have a concentration gradient
•Force directly proportional to the concentration gradient
Driving Forces- Electrical
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
Driving Forces- Electrochemical
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+
Types of Membrane Transport
2 main types:
Passive
Active
Passive
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)
Example; Glucose
GLUT4 carrier protein:
-Expressed in skeletal muscle and adipose tissue
-Glucose uptake by facilitated diffusion
-Expression upregulated by insulin
(A) In the absence of insulin, glucose cannot enter the cell
(B) Insulin signals the cell to insert GLUT 4 transporters into the membrane, allowing glucose to enter the cell
Example; Too much glucose in 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 (the point at which no more can be absorbed)
-Excess glucose can cause significant fetal harm
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
Active Transport
Requires an input of energy
Substance moves against its gradient (low to high)
Two types:
-Primary
-Secondary
Active Transport- Primary
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
When it 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
Active Transport- Secondary
Transport of a substance against its gradient COUPLED to the transport of an ion (usually Na+ or H+), which moves down its gradient
Secondary as doesn’t use energy directly from ATP but uses energy stored in the, for example Na+ gradient (from high to low), which was created using ATP
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
When it 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
Cellular signalling
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
When it 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 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
Endocytosis and exocytosis
Large molecules require different methods of transport:
- Endocytosis:
Transport into a cell - Exocytosis:
Transport out of a cell
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
