Glucose Homeostatis and Membrane Transport Flashcards
Describe the process off Secondary Active Transport
Secondary active transport is defined as the transport of a solute in the direction of its increasing electrochemical potential coupled to the facilitated diffusion of a second solute (usually an ion) in the direction of its decreasing electrochemical potential; It needs the gradient generated from the first solute.
(Primary transport, ATP is used to push solute from low to high concentration with no coupling)
Name the members of he glucose transporter family
x
What is a symporter?
A symporter is an integral membrane protein that is involved in movement of two or more DIFFERENT ions across a phospholipid membrane such as the plasma membrane in the SAME direction ( a type of cotransporter.)
What is an antiporter?
An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more DIFFERENT molecules or ions across plasma membrane in OPPOSITE directions.
What is the importance of Km values in relation to transporter function and tissue physiology?
x
What role does GLUT2 have in glucose homeostasis?
x
Name the two CLASSES of Glucose carriers.
1) Sodium-coupled glucose transporters
(in absorptive/reabsorptive EPITHELIAL cells like intestine/kidney where transport occurs acively against gradient)
2) Faciltative glucose transporters
CLASS 1 of glucose carrier.
Describe the stoichiometry (balance of equations) of Sodium coupled transporters
the energy from the Na+ gradient is used to transport substrates like glucose AGAINST their gradient.
Pump is at basal lateral side of intestine wall (lumen side) so glucose released into blood on the other side.
EQUILIBRIUM RATIO for the transported solute is given by a equation relating to the concentrating power of transporter to the sodium gradient and the coupling ratio (n)
as the coupling ratio increases, the potential [s]i/[s]o increases.
Due to energy loss, slippage of transporter and use of the gradient by other mechanisms equilibrum of [s]i and [s]o IS NOT ACHIEVED.
CLASS 1 of glucose carrier.
SYMPORTERS, such as the SGLT family, transport glucose
SGLT1: IN THE INTESTINE: has a high affinity of glucose (km=0.15mM) with a ratio of 1 sugar to 2 sodium. It allows a big concentration through but depends on sodium transport energy.
SGLT2: IN THE KIDNEY; has a LOW affinity (km higher at 2mM) with a ratio of 1 sugar to 1 sodium. It allows a smaller concentration through but only uses the energy generated form 1 sodium transport.
CLASS 1 of glucose carrier.
SYMPORTERS like ion coupled transporters of amino acids are selective for a certain type of amino acid. What are these types determined by?
1) Charge- aninic, cationic, neutral, zwitterionic
2) size (small or large)
3) structure
CLASS 1 of glucose carrier.
Name families of ion transporters
GAT family transports Na+ and Cl-
It has roles in inhibiting neurotransmission;
GAT1-3 IN GABA
GLYT1-2 IN GLYCINE
Describe Tertiary transport using the amino acids GLN, and LEU.
Primary transport : K out, Na+ into cell through the pump
Secondary Transport: SYSTEM A: na+ out cell enables GLN OUT of cell.
Tertiary Transport: SYSTEM L: GLN back INto cell allows LEU to EXIT cell in a hetroexchange.
CLASS 1 of glucose carrier.
SYMPORTERS, like NKCC (Na+ + k+ +Cl-) cotransporter is needed for epithelial NaCl absorption. Give some details.
They move each solute in the same direction. NKCC proteins maintain electroneutrality by moving two positively charged solutes (sodium and potassium) alongside two parts of a negatively charged solute (chloride). Thus the stoichiometry of the NKCC proteins is 1Na:1K:2Cl.
Sodium’s electrochemical gradient is established by the Na-K ATPase, which is an ATP-dependent enzyme. Since NKCC proteins use sodium’s gradient, their activity is indirectly dependent on ATP
NKCC1 is also expressed in many regions of the brain during early development, but not in adulthood.This change in NKCC1 presence seems to be responsible for altering responses to the neurotransmitters GABA and glycine from excitatory to inhibitory.
NKCC2 is found specifically in the kidney in nephrons apical membrane abutting the nephron’s lumen, the hollow space containing urine, where it extracts sodium, potassium, and chloride from the urine so that they can be reabsorbed into cells. Sodium goes on to be reabsorbed into the blood, where it contributes to the maintenance of blood pressure.
CLASS 1 of glucose carrier.
ANIPORTER like NHE1-5 (Na+ and H+ Exporter) have different functions. Name some of these functions.
1) Epithelial absorption and secretion [NHE 2,3,4] where NHE absorbs Na+ in the intestines as well as the renal HCO3- reabsorption and acid microclimate.
2) Cell volume regulation by NHE1
3) pH regulation by NHE 1 AND 5. pH 7 of cells is maintained by two antiporters: NA/H and CL/HCO3-
4) Internal H+modifier sites
It is inhibited by amiloride
Decribe the different functions of the ANTIPORTER NHE1 (CLASS 1 of glucose carrier.)
1) Ion translocation by ubiquitous NHE1 changes the 2) pH and cell volume which then changes 3) cell proliferation and migration. This is regulated by PHOSPHORYLATION,
1) NHE1 receptor in the membrane binds to the actin binding ERM proteins and becomes an anchor which acts to form the 2) cell shape and 3) cytoskeleton assembly as well as being used for 4) migraion, stress fibers, and adhesions
CLASS 1 of glucose carrier.
ANTIPORTER like NCX1-3 (Na+/Ca2+ exchanger) has a role in cardiac muscle cells. Give some details.
Receptor transports 3 Na+ for every 1 Ca2+.
Keeps calcium low in cells at 0.1 microM (where concentration is 2mM outside cell)
In the hear, if ouabain is used, pump is inhibited, less Na+ imported so less Ca2+ can be exported. This means inside concentration increases (NCX1 has no gradient to use) so contractile force INCREASES
CLASS 2 of glucose carrier
Give details of Facilitative glucose transporters.
1) They are on the surface as INTEGRAL proteins in ALL membranes.
2) It is an energy-independant process where glucose is transported DOWN THE GRADIENT (passive)
3) It can work bi-directionally in and out of cells or transcellular between cells as long as it travels along the gradient.
CLASS 2 of glucose carrier.
GLUT family
1) They are saturable
2) Contains 12 transmembrane proteins
3) Each member of the family have a unique 20 amino acids at the COOH terminus. This allows for specific antibody detection of receptors.
CLASS 2 of glucose carrier.
Give details of the different classes 1-3 of the GLUT family.
Identified through homology of sequences.
Class 1: GLUT 1, 3,4 are high affinity binding; GLUT 2 is low affinity
Class 2: GLUT 5,7,9,11 are VERY low affinity
Class 3: GLUT 6,8,10,12
CLASS 2 of glucose carrier.
What are the details of GLUT 1 from Class 1 of the GLUT Family?
km- 2-5
Expressed in the brain, RBC, and endothelial cells
CLASS 2 of glucose carrier.
What are the details of GLUT 2 from Class 1 of the GLUT Family?
km- 25
Expressed in kidney, small intestine, liver, pancreatic beta cells.
Role in sensing concentration of glucose in islets
GLUT2 involved in the mechanisms of glucosensing of pancreatic beta-cells, neuronal, or other cells, thereby playing a major role in the hormonal and neural control
It is never saturated (never plateus on graph of glucose uptake) whereas Glut 1 will be 90% saturated.
CLASS 2 of glucose carrier.
What are the details of GLUT 3 from Class 1 of the GLUT Family?
It has the lowest Km
Expressed in neurons and placenta.
In vitro; placenta saturated with glucose so fetus brain is supplied
CLASS 2 of glucose carrier.
What are the details of GLUT 4 from Class 1 of the GLUT Family?
Km- 2-10
Expressed in skeletal and cardiac muscle and adipose tissue.
Responds to insulin and has role in glucose regulation.
CLASS 2 of glucose carrier.
GLUT family and The role of insulin
GLUT 2 depolarises cell and allows insulin release by increasing cell calcium concentration.
GLUT 4 responds to insulin in tissues like muscles and fat, in particular getting rid of glucose after a meal when there is too much glucose in the blood.
