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Biomembranes > Membrane Transporter (Week 1) > Flashcards

Membrane Transporter (Week 1) Flashcards

1
Q

Extracelluar water of body fluid compartments

A

Plasma water 3L
Interstitial water 13L

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2
Q

What allows for transfer across the membrane

A

Electrochemical gradient

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3
Q

Is there a concentration gradient for k+

A

Yes

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4
Q

In the intracellular space what is the volume of water

A

25 L

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5
Q

How many ways can small molecules cross cell membranes

A

5

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6
Q

What are those 5 ways

A

Passive diffusion
Aqueous diffusion
Facilitated diffusion
Active transport
Endocytosis

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7
Q

Explain passive diffusion

A

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

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8
Q

What is a aquaporin

A

Membrane proteins that serve as channels in the transfer of water and in some cases small solutes across the membrane

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9
Q

Explain aqueous diffusion

A

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)

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10
Q

explain facilitated diffusion

A

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

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11
Q

explain active transport

A

via specialised carrier proteins Requires energy and can move molecules against the concentration gradient

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12
Q

explain Endocytosis (pinocytosis)

A

invagination of a part of the membrane. The molecule is encased in a small vesicle then ‘released’ inside the cell.

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13
Q

Explain the gradient of passive diffusion

A

It goes down a concentration gradient lipophilic molecule

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14
Q

Explain the concentration gradient of aqueous diffusion

A

Goes down the concentration gradient via a channel an ion channel

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15
Q

Explain the concentration gradient of facilitated diffusion

A

Down a concentration gradient via carrier protein it is also a chemical reaction

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16
Q

Explain the concentration gradient of active transport

A

Goes against a concentration gradient via carrier protein and it needs energy

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17
Q

What are passive diffusion and aqueous diffusion known as and explain it

A

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

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18
Q

Describe non-coupled transport

A

The movement of the solute is not dependent upon the movement of another solute or a chemical reaction taking place

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19
Q

What is the equation for electrochemical potential energy difference

A

Chemical potential energy + electrical potential energy difference

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20
Q

What is a equilibrium potential (Nernst equation)

A

The voltage necessary to offset the movement of an ion down an ions concentration gradient

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21
Q

lipid-water partition coefficient

A

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

22
Q

what does the proportion of ionization of a drug depend upon

A

both the pKa of the drug and the local pH

23
Q

what is the pH of the stomach and the plasma

A

stomach = 1.5
plasma = 7.4

24
Q

what happens to negativiley charged asprin

A

it diffuses across the membrane of the gastric mucosa and is trapped in the plasma

25
Q

where are the principal sites of carrier mediated transport (both facilitated diffusion and active transport)

A

blood brain barrier
gastrointestinal tract
placenta
renal tubule
Biliary tract

26
Q

name the importance of transporters

A

intestinal solute carrier protein, vital to the absorption of electrolytes, macro and micro-nutrients and vitamins also contribute to drug absorption

27
Q

how do hydrophilic polar molecules enter the cell

A

specialised carrier proteins that do not require energy

28
Q

what super family are glucose transporters (e.g. GLUT1) a part off

A

SLC2
SLC = solute carrier

29
Q

what is responsible for insulin secretion by pancreatic beta cells

A

facilitated diffusion of glucose by GLUT1

30
Q

what is responsible for the facilitated diffusion of fructose and glucose in the gut

A

GLUT2 and GLUT5

31
Q

what are glucose and galactose absorbed by

A

secondary active transport mediated by SGLT1

32
Q

what is fructose absorbed by

A

facilitated diffusion mediated by GLUT2

33
Q

which pump is the most important in primary active transport

A

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.

34
Q

what is primary active transport

A

moving a solute against its electrochemical gradient via ATP hydrolysis

35
Q

what is secondary active transport

A

moving a solte against its electrochemical gradient by coupling an “uphill” movement with the “downhill” movement of another solute.

36
Q

what is energy in the sodium gradient used for

A

to drive secondary active transport systems for sugars and amino acids

37
Q

catalytic subunits have binding sites for what

A

Na, K, ATP and Mg.
there are 4 isomers (a1 a2 a3 a4)
molecular size approx 112kDa

38
Q

explain the regulatory subunits

A

3 isomers (b1, b2, and b3)
heavily glycosylated (28% w/w) protein moity approx 35 kDa

39
Q

give examples of tissue specific expression of a subunit mRNAs

A

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)

40
Q

application to pharmacology digoxin

A

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.

41
Q

application to pharmacology-: P-glycoprotein transporters (another primary active transport system)

A

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

42
Q

what is the pump for primary active transport

A

Na+/K+ pump (antiport)

43
Q

what are the pumps for secondary active transport and give examples

A

Symport SGLT1-3
Antiport Na-Ca exchanger

44
Q

what are the major mechanisms of postprandial Na+ absorption in the jejunum

A

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-

45
Q

Primary and secondary transport and Na+ absorption. Na+/H+ exchange in the jejunum

A

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+

46
Q

Primary and secondary transport and Na+ absorption. briefly describe exchange at the apical membrane in the jejunum

A

Stimulated by the alkaline environment of the lumen (i.e. high pH = low proton concentration) due to the presence of bicarbonate from the pancreas

47
Q

Primary and secondary transport and Na+ absorption. Na+/H+ and CL-/ HCO3-

A

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+

48
Q

driving force for Na+

A

strongly negative, Na+ moves inward

49
Q

driving force for K+

A

fairly close to zero or somewhat positive, tends to move out of the cell

50
Q

driving force for Ca2+

A

always strongly negative tends to move into the cell down steep electrochemical gradient

Biomembranes (8 decks)

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