Carrier Mediated Transport

The Na+- glucose transmitter is a ______________ and requires a __________ electrochemical gradient

- symporter - Na+

Fill in the blanks: Of the total genetic material in a cell, _____-____% is derived from membrane proteins. In the case of neurons, ________% of the total energy consumption is used for these transport processes.

15-30% 66%

T or F: Carrier proteins readily form channels with openings on two sides of the membrane simultaneously.

False: Carrier proteins never form an open channel between the two sides of the membrane

What is the advantage of multi-pass transmembrane proteins? (AKA transporters or permeases)

Multi-pass proteins allow the hydrophilic solute to cross the membrane without coming into direct contact with the hydrophobic interior of the lipid bilayer.

Describe SERTs

Sodium and neurotransmitters, such as serotonin, can be coupled together through secondary active transport to allow for the reuptake and recycling of neurotransmitter •These transporters can act in reverse if the concentration gradient is higher inside of the cell of the pre-synaptic neuron. Also, if the membrane potential is positive (less negative ions), this too can reverse the function of the transporter.

The GLUT1 transporter is an example of what type of transporter?

carrier mediated transport/passive transport/facilitated diffusion

Define: Electrogenic

electrogenic means that the process will generate a membrane potential as it transports the solute across the plasma membrane.

Provide an example of uphill transport

•Active transport requires energy and goes against the electrochemical gradient.

Describe the mechanism for antiporters or exchangers

•Both solutes have to be present. •Transport is reversible. Directionality is determined by the electrochemical gradients for each of the solutes. •Can be electrogenic or electroneutral. Antiporter or exchanger carrier protein can also be utilized to make adjustments to pH or electrochemical gradients

Describe the symporter mechanism for carrier mediated transport

•Carrier protein has binding sites for two or more solutes. These sites are on alternate surfaces of the transporter. •Both solutes have to be present to work properly. •Co-transport can be electrogenic or electroneutral.

Describe pumps used for primary active transport

•Carrier protein is often called a "pump." •Can either transport a single solute or multiple solutes. •As long as the energy needed to move the solute against the electrochemical gradient agrees with the amount of chemical energy available from ATP, then pump will work properly.

Describe the enzymatic-like kinetics of carrier mediated transport

•Carriers will function according to Michaelis-Menten enzyme kinetics. •Maximum transport rate (Tm) is equal to the Jmax or Vmax. This indicates that it is a saturable process! •Km or Kt represents ½ of the Vmax and it is the affinity of the solute for the transporter. Transporters with a low Km will be able to transport the solute effectively at low concentrations. •The flux rate can also be influenced by the number of carriers. The more transporters placed in the plasma membrane, the higher amount of transport across the plasma membrane (e.g. insulin increases GLUT4 translocation to the membrane). •These carriers can be influenced by either COMPETITIVE INHIBITORS (bind to same site as solute) or NONCOMPETITIVE INHIBITORS (bind elsewhere and alter the structure of the transporter).

Describe what happens when the Na+/K+ pump becomes impaired

•Cell will lose K+ and will gain Na+. •This will cause for water to enter the cell and swell. •This pump is electrogenic- it contributes to the membrane potential because it pumps 3 positive ions out for every 2 positive ions in. •This "pump current" is hyperpolarizing (intracellular fluid is more negative than the extracellular fluid) and may change resting potential by as much as 10-20 mV.

Describe the activity of the drug digoxin

•Digoxin is an inhibitor of the Na+/K+ pump which can influence the Na+/Ca2+ exchanger and allow for intracellular calcium concentrations to increase. This will cause for an increase in cardiomyocyte contractility (referred to as a positive inotrope). •Digoxin, a drug utilized in heart failure, can bind to the Na+/K+ pump and cause for increased intracellular Na+ concentrations which will indirectly lessen the energy for the Na+/Ca2+ exchanger. •Ouabain, digoxin, or any drug that can bind to K+ binding pocket prevents the pump from getting dephosphorylated.

Define carrier-mediated transport

Carrier-mediated transport mechanisms are those in which a solute binds to a specific binding site on a carrier protein, an integral membrane protein, and then is transported to the other side of the membrane when the carrier's binding site is exposed to that opposite side of the membrane

Provide which of the type of molecules will need carrier proteins in order to cross the cell membrane: hydrophobic, ions, small uncharged polar molecules, large uncharged polar molecules.

Do not require carrier mediated transport: hydrophobic molecules, small uncharged polar molecules Require carrier mediated transport: large uncharged polar molecules, ions

Define: Electroneutral

Electroneutral indicates that the transporter does not generate a membrane potential.

Name the 3 classes of ATP-driven pumps

There are three classes of ATP-driven pumps: 1.P-type pumps are structurally and functionally related to the carrier proteins. They are called "P-type" because they phosphorylate themselves during the pumping cycle. This class includes many of the pumps responsible for setting up and maintaining gradients across cell membranes. Example: Na+/K+-ATPase 2.ABC transporters (ATP-Binding Cassette transporters) differ structurally from P-type ATPases and pump small molecules across the cell membrane. These transporters can efflux drugs (e.g. P-glycoprotein) or other small molecules, like high-density lipoprotein (HDL, e.g. ABCA1, ABCG1) 3.V-type pumps transfers hydrogen ion into organelles, such as lysosomes, synaptic vesicles, to acidify the interior of these organelles. In order to package a neurotransmitter into a vesicle, this pump has to be found on the vesicle. We do have drugs that can block these V-type pumps, however they are not used clinically due to significant adverse effects. The F-type pump is the ATP synthase found in mitochondria that help in the synthesis of ATP. These work opposite of V-type pumps because here you are using the hydrogen ion gradient to drive the synthesis of ADP to ATP.

T or F: Asymmetric distribution of transporters can be found in polarized cells. Examples of such are the gut lumen and neurons

True

T or F: BOTH a concentration gradient and an electrical gradient can help to drive passive transport

True

T or F: Channels are different than carrier proteins and will allow the opening between both sides of the cell membrane, interacting much weaker with the solute, and allow much more rapid of solute transfer across the membrane

True

T or F: While carriers function in a similar manner to enzymes, they will not change the substrate during transport. Enzymes, on the other hand, will change the substrate to form a product.

True

T or F: some small molecules like water, glycerol and ammonia are able to pass through channel proteins

True

T or F: light driven transport is a type of active transport

True, an example of such would be bacteriorhodopsin

Describe the Na+/K+ pump

•Helps to maintain the Na+ and K+ concentration gradients. •It is an electrogenic pump, by pumping 3 sodium ions outside of the cell and 2 potassium ions inside the cell. •Should be noted that this is minor and contributes to ONLY 10% of membrane potential. •It can indirectly influence other transporters, such as the Na+/Ca2+ exchanger and the transport of glucose and amino acids. •The Na+/K+ pump is a P-type pump that requires phosphorylation in order to induce the conformational change in the protein. •This pump helps to maintain the sodium and potassium concentrations for our cells. •This pump is electrogenic, however it contributes only a small portion of the membrane potential.

Differentiate primary active transport from secondary active transport

•Primary active transport are pumps that use ATP as an energy source. •Secondary active transport are transporters that use the potential energy available in the electrochemical gradient (e.g. sodium gradient is most common)

Describe SSRIs

•Serotonin reuptake inhibitors (SSRIs) are drugs that can block this mechanism and prevent the reuptake allowing for higher amounts of the neurotransmitter to remain in the synaptic cleft.

Provide 3 types of "downhill" transport

•Simple diffusion, passive transport, and facilitated diffusion are downhill processes that utilize potential energy from the concentration and electrical gradients.

Describe saturability in relationship to carrier mediated transport

•There are a finite number of carrier proteins on the cell membrane. When there is a large amount of solute present, all the carriers are occluded and the carrying capacity is at a maximum. •Once the carrier is saturated, then changing the concentration gradient by increasing the solute concentration WILL NOT increase the transport rate.

Describe specificity in relationship to carrier mediated transport

•There is one or more binding sites for the solute on the transporter. These binding sites give specificity for the particular solute. •Some carriers only recognize a specific molecule (absolute) •Others bind similar molecules or isomers (e.g. D-glucose versus D-galactose) •Others are fairly nonspecific (e.g. might work with a variety of amino acids)

Describes the actions you can take to alter the Na+/K+ pump

•To inhibit Na+/K+ pump: •Low sodium inside •Low potassium outside •Ouabain, digoxin, or any drug that can bind to K+ binding pocket prevents the pump from getting dephosphorylated. •Cooling or anoxia can limit ATP supply so they can slow the pump •To stimulate Na+/K+ pump: •Increase the intracellular Na+ concentration

Compare uniporters to symporters to antiporters

•Uniporter: transports a single solute •Symporter: transports more than one solute in the same direction. •Antiporter: transports more than one solute in the opposite direction.