LECTURE 6 (Membrane transport II) Flashcards
What are the three classes of Primary active pumps?
- P-class pumps (E1-E2 type pumps)
- ABC (ATP binding cassette) transporters
- FoF1 type pumps (ATP synthase complex)
What is the difference between a Uniporter, Symporter and Antiporter?
Uniporter = carries one molecule or ion
Symporter = carries two different molecules or ions in the same direction
Antiporter = carries two different molecules or ions in different directions
What equation shows the work performed by the cell when transporting against the gradient?
A = m R T ln C1/C2
A = work
m = substance mole quantity
C1 + C2 = substance concentrations in different compartments
R = gas constant
T = absolute temperature
What happens if substance is transported through electrically polarised membrane?
The work is performed against diffusion forces as well as electric forces of the membrane
What is Faraday’s number equal to?
1g-eqv ion charge
ATP-dependent ion pumps are grouped into classes based on what?
- Transport mechanism
- Genetic & Structural homology
What are the properties of Active transport?
- Carries out by pumps
- Pumps have high specificity and produce substance transport at high speed
- Main function of pumps = maintenance of gradients which are necessary for the life of the cell
- Pumps use energy from ATP-HYDROLYSIS or ENERGY OF LIGHT
What is ATP?
- The cell’s energy shuttle
- Composed of ribose (sugar), adenine (nitrogenous base) and three phosphate groups
What are the properties of ATP hydrolysis?
- Hydrolysis breaks bonds between terminal phosphate groups
- Exergonic reaction
- Release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves
What is the difference between Exergonic and Endergonic reactions?
Exergonic reactions (catabolism) -> drive the formation of ATP (endergonic)
Endergonic reactions (cellular work) -> drive the hydrolysis of ATP (exergonic)
Describe the Na+/K+ pump
- Expressed on plasma membranes of highest eukaryotes
- High content in nerve cells
- Integral glycoprotein
- Contains 4 subunits (two alpha + two beta)
Describe the alpha and beta subunits of the Na+/K+ pump
SMALL BETA SUBUNITS
- outer surface of membrane
- join to membrane through oligosaccharides
- contains only 1 transmembrane domain
LARGE ALPHA SUBUNITS
- enzymatic activity
- 8-10 transmembrane domains
- P-PO4 and N (nucleotide connective) intracellular subunits
Describe how the Na/K+ pump works
1) Na+ in cytoplasmic side bind to the pump which causes it to be phosphorylated + conformational change -> binding site of ions moves to outer side of membrane -> STRONG ELECTROSTATIC REPULSION BETWEEN NA+ IONS -> ions released in extracellular space
2) conformational change -> bound Na+ faces outside + binding sites are altered -> ions released into intracellular space
3) 3 Na+ ions out, 2 K+ ions in
What is Ouabain?
Ouabain (G-STROPHANTHIN) is a plant-derived toxic substance traditionally used as an arrow poison in Eastern Africa.
Small doses = treats Hypotension, Angina Pectoris, Cardiac Arrhythmias
Large doses = can cause death
- Rapid twitching of the neck and chest muscles
- Respiratory distress
- Increased and irregular heartbeat
- Rise in blood pressure
- Convulsions
- Wheezing
- Clicking and Gasping rattling
MECHANISM:
blocks Na+/K+ ATPase -> Intracellular Na+ remains high -> Na+/Ca+ antiport cannot remove Ca+ ions from the cardiac muscles -> Intensification of myocardium contraction activity -> heart rate falls and increase in power -> accumulation of intracellular Na+ ions in cardiomyocytes sarcoplasm -> decrease in myocardium excitation -> rhythm functional changes
Describe the Ca2+ ATPase pump
- Maintains maintenance of Ca2+ low content
- Transport calcium from cytoplasm in the intracellular space
- Located in Sarcoplasmic reticulum
- Small cytoplasmic Ca2+ concentration compared with extracellular Ca2+
What is control of Ca2+ important for?
- Transmitter release
- Ion channel activation
- Regulation of cytoplasmic enzymes
What is the formation of the Ca2+ ATPase pump?
- 2 subunits (large alpha + small beta)
- Alpha subunit has Ca2+ ion binding + AMINOACYL RESIDUE in phosphorylating process
- For every 1 ATP molecule, 2 Ca2+ ions
What do mutations of Ca2+ ATPase result in?
Disorders of relaxation of skeletal muscle and tone increase
Describe the Gastric mucosal H+/K+ ATPase
- Integral membrane protein located on membranes connected with tubovascular and secretory channels of parietal cells
- H+ ions in the secretory channels of parietal cells
- 2 alpha + 2 beta subunits
[ beta = regulatory role, alpha = H+ ions connective site and aspartate aminoacyl residue sites (phosphorylation) ]
Which drugs are Proton pump inhibitors?
- Omeprazole
- Lansoprazole
- Pantoprazole
- Rabeprazole
What is the function of P-type ATPases?
Ensure heavy metal transport in the cell membrane
What is Menkes disease?
A disease caused by a defective ATP 7A gene that regulates the metabolism of copper in the body which primarily affects male infants
CAUSES:
Copper accumulates at ABNORMALLY LOW levels in the LIVER and BRAIN but HIGHER than normal in the KIDNEY and INTESTINAL LINING -> Affected infants born prematurely but seem normal at birth -> Symptoms appear after 6-8 weeks
SYMPTOMS:
- Floppy muscle tone
- Seizures
- Failure to thrive
- Subnormal body temperature
- Kinky, colourless/steel-coloured hair that breaks easily
- Extensive neurodegeneration of brain
- Osteoporosis
- Arterial dissection
What is Wilson disease?
An autosomal recessive disorder that is caused by a mutation in gene ATP7B which prevents the body from expelling excess copper
CAUSES:
Copper builds up in the liver, brain, kidneys and eyes and over time the copper causes irreversible organ damage
TREATMENT:
- Penicillamine (removes excess copper with a zinc supplement)
Describe ABC (ATP binding cassette) transporters
Transmembrane proteins that utilise the energy of ATP hydrolysis to carry out certain biological processes
PROPERTIES:
- 6/12 transmembrane helices with 2 ATP binding sites
- Translocate substances across membranes, translation of RNA & DNA repair
- Resistant to several drugs
What happens in the Electron transport chain?
Electrons are passed from one protein in the transport chain to another in a series of REDOX REACTIONS -> Energy released is captured as a proton gradient used to make ATP (CHEMIOSMOSIS) -> Electron transport chain make up OXIDATIVE PHOSPHORYLATION
What are the steps of Oxidative phosphorylation?
1) Delivery of electrons by NADH and FADH
2) Electron transfer and proton pumping
3) Splitting of oxygen to form water
4) Gradient-driven synthesis of ATP
What is the difference between NADH and FADH?
NADH
- very good at donating electrons in redox reactions
- transfers electrons directly to complex I
- energy released + used to pump protons from matrix to inter membrane space
FADH
- not good at donating electrons
- transfers electrons to complex II
- does not pump protons across membrane
What happens after NADH and FADH donate electrons?
Both complex I and II pass electrons to UNIQUINONE (Q) which is reduced to QH and travels through membrane -> delivers electrons to complex III -> more H+ pumped across membrane -> electrons delivered to CYTOCHROME C -> electrons moved to complex IV where electrons are passed to O2 to form H2O
What is the function of the F-type pump?
- Ensures the transport of protons from the mitochondrial matrix into the inter membrane space with ATP hydrolysis
- Eliminates H+ gradient from inter membrane space into matrix + catalyses synthesis of ATP
What are the inhibitors of F-type receptors?
Function: block H+ transport coupled to ATP synthesis or hydrolysis
INHIBITORS
- Oligomycin
- DCCD (dicyclohexylcarbodiimide) = reacts with carboxyl groups in hydrophobic environments forming a covalent adduct
What happens in Brown fat?
Brown fat = participates in body thermal regulation
Brown fat mitochondria contain the UNIPORTER OF MITOCHONDRIAL MEMBRANES (UCP) -> UCP uncouples H+ flow from ATP synthesis by dissipating the proton gradient -> Instead of flowing through ATP synthase, protons escape through UCP uniporter and produce heat (do not produce ATP)
What happens in Secondary Active Transport?
The movement of a driving ion down an electrochemical gradient is used to drive the uphill transport of another ion/molecule against a concentration/electrochemical gradient
What are the two types of Active transport?
Cotransport = direction of transport is the same for both the driving ion and driven ion/molecule
Exchange = driving ion and driven ion/molecule move in opposite directions
Define Concentrative capacity
A measure of how well the driven ion/molecule is concentrated against a concentration gradient
[defines the effectiveness of the transport process]
What is the difference between Electrogenic/Electroneutral cotransporters/exchangers?
Electrogenic = A transporter that leads to the net translocation of charge across the membrane
Electroneutral = When no net charge is transported across the membrane per transport cycle
What is the function of Kidneys?
- Regulate concentration of electrolytes and water in the organism
- Acid-base balance
- Excretion of toxic metabolites
- Filtration/reabsorption mechanisms
Describe the reabsorption of glucose in the kidneys
1) In APICAL MEMBRANE of epitheliocytes of RENAL TUBULES glucose is transported through SYMPORT with Na+ (SGLT1/2)
2) In opposite site of cell towards interstitial fluid there is facilitated passive transporter GLUT-2 -> causes glucose passive diffusion towards PERITUBULAR BLOOD CAPILLARY -> Returns glucose back to circulatory system
