Name the 2 different ways to achieve diffusion?
Bilayer or channel
Define "primary active transport"?
Use of ATP to transport a solute against its concentration gradient.
Define "secondary active transport"?
Symport. Use of the energy retrieved from a solute going with its concentration gradient as the energy source for a solute going against its.
The solutes are going in the same direction
The solutes are getting transported in different directions
Why is glucose oxidation important?
Represents a major source of energy in mammalian cells.
Why is it important for the glucose oxidation to get into the cells?
In order to utilise the energy from it
Name the two different classes of glucose carriers that is important in transferring glucose across the plasma membrane?
1. Sodium-coupled glucose transporters 2. Facilitative glucose transporters
Where is the sodium- dependent glucose cotransporter expressed?
In absorptive/reabsorptive epithelia such as intestine and kidney.
Define the characteristics of the sodium-coupled glucose transporters?
Glucose transport occurs actively against its concentration gradient by coupling glucose uptake with that of sodium.
Why do cells need energy?
In order to maintain basic function.
Give an example of a primary active transporter that brings in glucose into the cell?
Give an example of a secondary active transporter that brings in glucose into the cell?
SGLT. (sodium-glucose linked transporter) Brings in sodium and glucose.
The important of the sodium-potassium pump when thinking of glucose homeostasis?
It actively removes sodium from the cell (therefore making the concentration of sodium low in the cell). This is important as the SGLT brings it in.
Sodium coupling ratio. eg. 2 Na: 1 Glucose for SGLT
Give an example of a tertiary active transporter that brings glucose into the cell?
Proton coupled active transporter (H+)
What is the equilibrium ratio for co-transported solute?
[S]I/[S]O = ([Na]O/[Na]i) ^n . (e^-FE/RT)^n*. =Chemical gradient x electrical gradient
What does the "n" stand for in the equilibrium ratio for co-transported solute?
What does the " * " stand for in the equilibrium ratio for co-transported solute?
Charge of the ion. ie. Na^2+ : therefore *= 2
What is the names given to the two members of the SGLT family?
1. SGLT1 2. SGLT2
High affinity. 2 sodium: 1 glucose. seen in the intestines
Low affinity. 1 sodium: 1 glucose. Seen in the kidneys
Name the three types of secondary active transporters: symporters?
1. SGLT family 2. Ion coupled transporters of amino acids 3. NKCC
How many common amino acids are there that can be used in the ion-coupled transporters of AA?
What are the three variables that determine the amino acids transporter that is selected for a specific amino acid substrate?
1. Charge 2. Size 3. Structure
Define the "GAT family"?
Family of sodium chloride coupled transporters
Name the two groups of member in the GAT family?
1. GAT 1-3 (for GABA) 2. GLY1-2 (for glycine)
What is the role of the GAT family?
Roles in inhibitory neurotransmission
Its when two different solutes are coupled in the active transport
Define "tertiary active transporter"
Use of the energy retrieved by secondary transport as the source of energy to transport new solutes.
Name the primary, secondary and tertiary active transport used to transport amino acids (Gln, Leu)?
Primary: Sodium pump Secondary: System A Tertiary: System L
NKCC cotransporters properties?
1 Na: 1 K: 2 Cl: all solutes come into the cell-> water removed Inhibition by bumetanide > piretanide > furosemide: promotes water loss from the body.
NKCC cotransporter functions?
Cotransport in epithelial NaCl absorption Promotes water loss from cell Cell volume regulation Modulation of neurotransmission
Name the two types of secondary active transporters: anti porters?
1. Na/H exchangers (NHE1-5) 2. Na/Ca exchange (NCX1)
What are the 3 functions of the Na/H exchangers?
1. Epithelial absorption and secretion 2. Cell volume regulation 3. pH regulation
How many members are in the Na/H exchanger family?
What does each member do as a function?
NHE 2->4 : Epithelial absorption and secretion NHE1: Cell volume regulation NHE 1,5: pH regulation
How does the Na/H exchanger regulate pH? Additionally what pH?
The activity reacts to low pH levels. ie. if there is a lot of acidic inside the cell there is a need to remove it therefore the activity increases.
What is use to regulate high pH?
Cl/HCO3 antiporter. Activity increases at high pH to reduce the pH to normal. Works beside Na/H exchanger.
What modulates the NHE1 activity?
How does the NHE 1 function as a cell volume regulator?
The ubiquitous NHE1 translocates ions that change the pH and cell volume- regulating cell proliferation and migration.
How does the NHE1 help in cytoskeletal assembly and cell shape determination?
NHE1 binds directly to ERM proteins and acts as a membrane anchor which is critical for these assemblies.
Name the 3 properties of the sodium/ calcium exchanger?
1. Na inwards/ Ca outwards usual, notably in cardiac muscle. 2. Contributes to keeping cell calcium conc low. 3. 3 Na: 1 Ca
Ouabain use during a heart failure?
Reduces calcium gradient. Cell calcium increases due to reduced NXC1 activity. Increases contractile force.
How many transmembrane domains are there in the SGLT?
13 transmembrane domains
Where abouts in the body is SGLT1 found?
In the intestines.
Where in the body is SGLT2 found?
In the kidneys
Describe how the SGL transporter actually works?
Describe the 5 properties of the facilitative glucose transporters?
1. Integral membrane proteins. 2. Present on the surface of all cell membranes. 3. Transport glucose down a concentration gradient. 4. Energy independent. 5. Can operate bi-directionally
How does GLUT1 work?
Name the 3 properties of the facilitative GLUT family?
1. 13 functional facilitated hexose carriers 2. Saturable, stereoselective 3. 12 Transmembrane domains.
What part of the facilitative GLUT is important for different antibodies to bind?
Unique last 20 AAs which determine what antibodies binds.
How many classes of GLUTs are there?
3. Class 1, 2 and 3
Define the properties of Class 1 GLUT and the different members in it?
Comprises the well-characterised glucose transporters. High affinity: GLUT 1, 3, 4 Low affinity: GLUT 2
Define the properties of Class 2 GLUT and the different members in it?
Very low affinity for glucose (transport fructose). GLUT 5, 7, 9, 11. HMIT1
Define the properties of Class 3 GLUT and the different members in it?
GLUT 6, 8, 10, 12
Characteristics of GLUT 1?
House keeping sugar transporter. Widely expressed.
Characteristics of GLUT 2?
Low affinity glucose transporter. Will never be saturated. Role in sensing glucose concentrations in islets.
Characteristics of GLUT 3?
Important in the foetus. High affinity. Ensures the foetus has enough glucose. Important in the brain also as the brain can metabolise fatty acids therefore needs glucose.
Characteristics of GLUT 4?
Important in insulin targeting tissues ie. skeletal, cardiac muscle and adipose tissue.
What are the Km values for each of the GLUTS?
How does GLUT2 affect the islets in the pancreas?
When there is a high level of glucose outside the GLUT2 brings in glucose. Undergoes glycolysis producing ATP. This opens the ATP sensitive K channel causing a depolarisation inside the cell. In turn, opening the calcium channel (sensitive to voltage). This increase in calcium stimulates exocytosis of the vesicles containing insulin.
What is the GLUT4 responsible for?
Mediating insulin-sensitive glucose transport Important for facilitating peripheral glucose disposal after a meal when blood glucose is high
What does cytochalasin B do?
Specifically binds to facilitative glucose transporters in a non-competitive manner. Inhibits cell division
GLUT 4 expression after a meal?
Insulin is produced straight after a meal. Stimulates the movement of GLUT4 from the inner membrane to the plasma membrane and therefore facilitative transport of glucose into the cell. Found in fat cell as well as muscle.