Membrane Transporter (Week 1) Flashcards
Extracelluar water of body fluid compartments
Plasma water 3L
Interstitial water 13L
What allows for transfer across the membrane
Electrochemical gradient
Is there a concentration gradient for k+
Yes
In the intracellular space what is the volume of water
25 L
How many ways can small molecules cross cell membranes
5
What are those 5 ways
Passive diffusion
Aqueous diffusion
Facilitated diffusion
Active transport
Endocytosis
Explain passive diffusion
No vehicle is needed for lipophilic molecules to pass through the cell membrane
Moving from an area of high concentration to low concentration
Through aqueous pores formed by aquaporins
What is a aquaporin
Membrane proteins that serve as channels in the transfer of water and in some cases small solutes across the membrane
Explain aqueous diffusion
Moves through a channel that transverse the plasma membrane.
Does not require energy but requires concentration gradient
Molecules also need a vehicle to pass though (ion channel)
explain facilitated diffusion
diffuse via specialised carrier proteins that bind the drug on one side of the bind molecule on one side of the membrane then change conformation and release on the other side. Does not require energy, but does require a concentration gradient
explain active transport
via specialised carrier proteins Requires energy and can move molecules against the concentration gradient
explain Endocytosis (pinocytosis)
invagination of a part of the membrane. The molecule is encased in a small vesicle then ‘released’ inside the cell.
Explain the gradient of passive diffusion
It goes down a concentration gradient lipophilic molecule
Explain the concentration gradient of aqueous diffusion
Goes down the concentration gradient via a channel an ion channel
Explain the concentration gradient of facilitated diffusion
Down a concentration gradient via carrier protein it is also a chemical reaction
Explain the concentration gradient of active transport
Goes against a concentration gradient via carrier protein and it needs energy
What are passive diffusion and aqueous diffusion known as and explain it
Known as non-coupled transport, a solute moves down its chemical or electrical gradient. The membrane will have to be permeable, either the solute will have appropriate lipophilicity to simply cross the membrane or channels will have to be present in the membrane
Describe non-coupled transport
The movement of the solute is not dependent upon the movement of another solute or a chemical reaction taking place
What is the equation for electrochemical potential energy difference
Chemical potential energy + electrical potential energy difference
What is a equilibrium potential (Nernst equation)
The voltage necessary to offset the movement of an ion down an ions concentration gradient
lipid-water partition coefficient
helps measure how lipid or water soluble a drug is. This is determined by how readily a drug partitions between hexane and water.
for hydrophobic molecules Kp< 1
for hydrophilic molecules Kp >1
what does the proportion of ionization of a drug depend upon
both the pKa of the drug and the local pH
what is the pH of the stomach and the plasma
stomach = 1.5
plasma = 7.4
what happens to negativiley charged asprin
it diffuses across the membrane of the gastric mucosa and is trapped in the plasma
where are the principal sites of carrier mediated transport (both facilitated diffusion and active transport)
blood brain barrier
gastrointestinal tract
placenta
renal tubule
Biliary tract
name the importance of transporters
intestinal solute carrier protein, vital to the absorption of electrolytes, macro and micro-nutrients and vitamins also contribute to drug absorption
how do hydrophilic polar molecules enter the cell
specialised carrier proteins that do not require energy
what super family are glucose transporters (e.g. GLUT1) a part off
SLC2
SLC = solute carrier
what is responsible for insulin secretion by pancreatic beta cells
facilitated diffusion of glucose by GLUT1
what is responsible for the facilitated diffusion of fructose and glucose in the gut
GLUT2 and GLUT5
what are glucose and galactose absorbed by
secondary active transport mediated by SGLT1
what is fructose absorbed by
facilitated diffusion mediated by GLUT2
which pump is the most important in primary active transport
Na+/K+ ATPase pump, this is because it sets up for the concentration gradients for secondary active transport mechanisms.
this pump actively transports three sodium ions (Na+) out of the cell and two potassium ions (K+) into the cell against their respective concentration gradients. This process is crucial for maintaining the resting membrane potential in excitable cells like neurons and muscle cells.
what is primary active transport
moving a solute against its electrochemical gradient via ATP hydrolysis
what is secondary active transport
moving a solte against its electrochemical gradient by coupling an “uphill” movement with the “downhill” movement of another solute.
what is energy in the sodium gradient used for
to drive secondary active transport systems for sugars and amino acids
catalytic subunits have binding sites for what
Na, K, ATP and Mg.
there are 4 isomers (a1 a2 a3 a4)
molecular size approx 112kDa
explain the regulatory subunits
3 isomers (b1, b2, and b3)
heavily glycosylated (28% w/w) protein moity approx 35 kDa
give examples of tissue specific expression of a subunit mRNAs
a1 - Ubiquitous expression - contains the binding site for drugs such as digoxin (found and active in nearly all cells and tissues)
a2 - excitable tissues/ insulin responsive tissues
a3 - excitable tissues
a4 - only expressed in spermatozoa (only in the testis)
application to pharmacology digoxin
obtained from foxglove
Alters the heart rate
Is an inhibitor of Na+/K+ ATPase pump and binds to alpha subunits.
Causes increase in intracellular Na+ concentration, reduces the action of the Na+/ Ca2+ exchanger, means more intracellular Ca2+ later stored in the sarcoplasmic reticulum.
Ca2+ released during a cardiac action potential increasing force of a contraction.
application to pharmacology-: P-glycoprotein transporters (another primary active transport system)
multidrug transmembrane transporters (ATP dependant)
responsible for multi-drug resistance
functions in various parts of the body such as:
- liver: transporting drugs into bile for elimination
- kidneys: pumping drugs into urine for excretion
- placenta: transporting drugs back into maternal blood
- intestines: transporting drugs into intestinal lumen, reducing drugs absorption into the blood
- brain capillaries: pumping drugs back into the blood, limiting distribution in the brain
what is the pump for primary active transport
Na+/K+ pump (antiport)
what are the pumps for secondary active transport and give examples
Symport SGLT1-3
Antiport Na-Ca exchanger
what are the major mechanisms of postprandial Na+ absorption in the jejunum
Na+/ glucose and Na+/amino acids
both of these are examples of secondary active transport and are electrogenic, as is the Na+/K+ ATPase- collectively the overall transport of the Na+ generates a trans epithelial potential (Vte) in which the lumen is negative- this drives the parallel absorption of CL-
Primary and secondary transport and Na+ absorption. Na+/H+ exchange in the jejunum
this occurs at both the apical (NHE2 and NHE3) and the basolateral (NHE1) membranes, only NHE2 and NHE3 contribute to transepithelial movement of the Na+
Primary and secondary transport and Na+ absorption. briefly describe exchange at the apical membrane in the jejunum
Stimulated by the alkaline environment of the lumen (i.e. high pH = low proton concentration) due to the presence of bicarbonate from the pancreas
Primary and secondary transport and Na+ absorption. Na+/H+ and CL-/ HCO3-
this exchanges in parallel and occurs in the ileum and proximal colon and is the primary mechanism of the Na+ absorption in the inter digestive period, does not contribute greatly to postprandial absorption.
absoption is electroneutral
regulated by intracellular cAMP, cGMP and Ca2+
driving force for Na+
strongly negative, Na+ moves inward
driving force for K+
fairly close to zero or somewhat positive, tends to move out of the cell
driving force for Ca2+
always strongly negative tends to move into the cell down steep electrochemical gradient
