Glucose Homeostatis and Membrane Transport Flashcards

1
Q

Describe the process off Secondary Active Transport

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name the members of he glucose transporter family

A

x

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a symporter?

A

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.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is an antiporter?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the importance of Km values in relation to transporter function and tissue physiology?

A

x

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What role does GLUT2 have in glucose homeostasis?

A

x

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Name the two CLASSES of Glucose carriers.

A

1) Sodium-coupled glucose transporters
(in absorptive/reabsorptive EPITHELIAL cells like intestine/kidney where transport occurs acively against gradient)

2) Faciltative glucose transporters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

CLASS 1 of glucose carrier.

Describe the stoichiometry (balance of equations) of Sodium coupled transporters

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

CLASS 1 of glucose carrier.

SYMPORTERS, such as the SGLT family, transport glucose

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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?

A

1) Charge- aninic, cationic, neutral, zwitterionic
2) size (small or large)
3) structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

CLASS 1 of glucose carrier.

Name families of ion transporters

A

GAT family transports Na+ and Cl-

It has roles in inhibiting neurotransmission;
GAT1-3 IN GABA

GLYT1-2 IN GLYCINE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe Tertiary transport using the amino acids GLN, and LEU.

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CLASS 1 of glucose carrier.

SYMPORTERS, like NKCC (Na+ + k+ +Cl-) cotransporter is needed for epithelial NaCl absorption. Give some details.

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CLASS 1 of glucose carrier.

ANIPORTER like NHE1-5 (Na+ and H+ Exporter) have different functions. Name some of these functions.

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Decribe the different functions of the ANTIPORTER NHE1 (CLASS 1 of glucose carrier.)

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

CLASS 1 of glucose carrier.

ANTIPORTER like NCX1-3 (Na+/Ca2+ exchanger) has a role in cardiac muscle cells. Give some details.

A

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

17
Q

CLASS 2 of glucose carrier

Give details of Facilitative glucose transporters.

A

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.

18
Q

CLASS 2 of glucose carrier.

GLUT family

A

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.

19
Q

CLASS 2 of glucose carrier.

Give details of the different classes 1-3 of the GLUT family.

A

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

20
Q

CLASS 2 of glucose carrier.

What are the details of GLUT 1 from Class 1 of the GLUT Family?

A

km- 2-5

Expressed in the brain, RBC, and endothelial cells

21
Q

CLASS 2 of glucose carrier.

What are the details of GLUT 2 from Class 1 of the GLUT Family?

A

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.

22
Q

CLASS 2 of glucose carrier.

What are the details of GLUT 3 from Class 1 of the GLUT Family?

A

It has the lowest Km

Expressed in neurons and placenta.

In vitro; placenta saturated with glucose so fetus brain is supplied

23
Q

CLASS 2 of glucose carrier.

What are the details of GLUT 4 from Class 1 of the GLUT Family?

A

Km- 2-10

Expressed in skeletal and cardiac muscle and adipose tissue.

Responds to insulin and has role in glucose regulation.

24
Q

CLASS 2 of glucose carrier.

GLUT family and The role of insulin

A

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.

25
Q

CLASS 2 of glucose carrier.

Describe the EXPERIMENT testing the mechanism i which insulin stimulates glucose transport in rat fat cells

A

Metabolite called CB binds specifically to glucose transporters (non competitively) at the cytoplasmic domain of the transporter.

As a result, cell division, movement and glucose transport was inhibited and induces nuclear extrusion. Microfilaments and actin polymerization are interfered.

The amount of transporters inhibited in the membranes of a insulin and non insulin treated fat cell are calculated.

In insulin fat cells there was more CB bound even though the affinity for binding was lower in these cells.

SO INSULIN MUST INCREASE THE TRANSLOCATION OF GLUT TRANSPORTERS FROM IM TO PM, HELPING GLUCOSE TRANSPORT.

Antibodies proved was insulin caused an increase in the PM and a decrease in the IM of the GLUT4 transporter.

26
Q

CLASS 2 of glucose carrier.

Describe the IMPORTANCE of the mechanism i which insulin stimulates glucose transport in rat fat cells

A

1) Muscle is principle for glucose use
2) Muscle principle for insulin targetting
3) Muscle must be fully responsive to insulin in order to lower the blood glucose via a functional transporT system. (GLUT4)

One of the causes of Diabetes if muscle is not sensitive or GLUT 4 defected.

27
Q

How can a chimera of GLUT 4 and florescent GFP CONFIRM insulin causes transporter translocation

A

The florescence of the chimera can be detected at the cell plasma membrane after insulin treatment; migration shown.

28
Q

What is the significance of Km values in relation to transporter function and tissue physiology?

A

The Km value for GLUT proteins is the concentration of blood glucose at which transport into the cell takes place at half its maximum rate.

A Km of 3-7 mM (GLUT 1) is below or equal to the average blood glucose concentration of 5-7 mM, enabling tissues to take up glucose at a significant rate, regardless of the amount present in the blood.

29
Q

Describe Glucose homeostatis and GLUT 4/insulin.

A

When insulin binds to the insulin receptor it initiates a signaling cascade that leads to the translocation of GLUT4 glucose transporter vesicles to the plasma membrane. Fusion of GLUT4 storage vesicles with the plasma membrane in response to insulin results in an increase in the amount of GLUT4 on the cell surface, thereby increasing the transport of glucose into the cell. Insulin signaling also inhibits GLUT4 endocytosis ensuring a longer duration of GLUT4 residence in the plasma membrane.