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Physiology I: Cellular Neuro > Lecture 4: Mediated Transport > Flashcards

Lecture 4: Mediated Transport Flashcards

1
Q

Common properties of protein mediated transport

A
  • Involve interaction with protein carrier
  • Show saturation characteristics
  • Have maximum rate of transportation
  • Show chemical and stereo-specificity
  • Show competition
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2
Q

Facilitated diffusion characteristics

A
  • Requires no energy
  • Driving force is Delta[Solute]
  • Works downhill
  • Cannot move solute against its [ ] gradient
  • Inhibited by specific poisons
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3
Q

Examples of facilitated diffusion

A
  • GLUTs

- UTs

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4
Q

Specific characteristics of primary active transport

A
  • Requires energy at site of transportation
  • Transports solute against concentration gradient (uphill)
  • Phosphorylation of carrier occurs
  • Inhibited by specific and metabolic poisons
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5
Q

Specific characteristics of secondary active transport

A
  • Requires energy, but NOT AT SITE of transportation
  • Transports solute of interest against concentration gradient (uphill)
  • Powered by another solute moving down its concentration gradient
  • Specific characteristics
  • No phosphorylation of carrier involved
  • Inhibited by metabolic and specific poisons
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6
Q

ATP Binding Cassette (ABC Transporer)

A
  • Contain aa sequences (cassette) that bind ATP
  • ATP catalysis not necessarily coupled to transport
  • Can behave like pumps, channels or regulators
  • Multi Drug Resistance transporters, MDR
  • Cystic Fibrosis Transmembrane conductance Regulator, CFTR
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7
Q

Mediated transport requires

A
  • Physical interaction between transporter and transported substance
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8
Q

Three types of mediated transport

A
  • Facilitated diffusion (passive)
  • Primary active transport
  • Secondary active transport
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9
Q

Active systems

A
  • Require energy

- Move substance against its concentration gradient

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10
Q

Epithelial transport uses

A
  • A variety of transport systems to cross cellular barriers
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11
Q

Mediated transport systems require

A
  • Intrinsic membrane proteins that act as transporters (carriers)
  • Molecule that would normally move very slowly, if at all, across the lipid bilayer
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12
Q

Saturation

A
  • A maximum rate of transportation
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13
Q

Specificity

A
  • Transport only one type of solute (mostly)
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14
Q

Competition

A
  • Similar sized and shaped molecules can inhibit transport
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15
Q

Facilitated diffusion moves atoms, ions, and molecules

A
  • Down a concentration gradient

- Via interaction with a transport protein

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16
Q

The driving force for movement is

A
  • The concentration gradient of solute
  • It acts to equalize the concentration inside and outside cells
  • No metabolic energy is required
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17
Q

The rate of glucose transport into the RBC via facilitated diffusion is

A
  • Greater than predicted from the glucose partition coefficient
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18
Q

Glucose entry as a function of glucose concentration

A
  • Deviates from the diffusion law
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19
Q

Glucose transport has

A
  • Maximal rate of transport (Vmax)

- Km (recall Km is an index of the affinity of the transport system for the transported substance)

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20
Q

Glucose entry

A
  • Stereospecific
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21
Q

D-glucose enters the cell

A
  • Rapidly

- Km = 1.5mM

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22
Q

D-galactose enters the cell

A
  • More slowly

- Km = 30mM

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23
Q

L-glucose enters the cell

A
  • Not at all

- Km = 3000mM

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24
Q

Others sugars transported via D-glucose systems include

A
  • D-mannose
  • D-xylose
  • L- arabinose
  • All have Km’s greater than glucose
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25
Q

Systems can be inhibited by specific poisons such as

A
  • HgCl2

- Dinitrofluorobenzene

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26
Q

Systems are not affected by non-specific metabolic poisons such as

A
  • Cyanide

- Dinitrophenol

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27
Q

Examples of facilitated diffusion

A
  • Sugars

- Urea

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28
Q

Sugars (facilitated diffusion) diffuse into

A
  • RBC
  • WBC
  • Myocytes
  • Adipocytes
  • Choroid plexus
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29
Q

Large family of transporters for sugars include

A
  • GLUT (14 members currently)

- One of which is insulin dependent (GLUT 4)

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30
Q

Insulin increases rate of glucose transport in

A
  • Myocytes

- Adipocytes

31
Q

Urea (facilitated diffusion) found in

A
  • Collecting duct of nephrons

- Transport urea out of duct

32
Q

Amino acids (facilitated diffusion) diffuse into

A
  • RBC & WBC
  • Out of intestinal epithelium
  • Wide variety of systems
  • At least 3 basic types
33
Q

Active transport

A
  • Moves atoms, ions, molecules against a concentration gradient
  • Helps maintain concentration differences across permeable barriers
34
Q

In active transport,

A
  • Work must be done
  • Energy (ATP) is required
  • Directly in primary active transport
  • Secondarily in secondary active transport
35
Q

Active transport shares

A
  • All the characteristics of mediated transport systems
36
Q

Primary active transport energy consumption

A
  • 1/3 total resting energy (ATP) consumption of humans is used in pumping these ions
37
Q

In primary active transport, gradients control

A
  • Cell volume
  • Membrane excitability
  • Drive sodium cotransport of sugars/amino acids/nutrients
38
Q

Concentration gradients in primary active transport are maintained by

A
  • Na+/K+ ATPase

- Located in the plasma membrane

39
Q

Intracellularly, most cells have a _____ concentration of K+ and a _____ concentration of Na+

A
  • High [K+]

- Low [Na+]

40
Q

Model of Na+/K+ ATPase

A
  • 3Na+ out, 2K+ in, 1ATP consumed
  • Protein: at least 4 conformational states
  • ATP must bind/energize the carrier
  • ATP is not hydrolyzed unless sodium and
    potassium are transported
41
Q

Na+/K+ ATPase is electrogenic

A
  • Generates an electrical current in the plasma membrane
42
Q

Na+/K+ ATPase pump can be reversed

A
  • To synthesize ATP
43
Q

Cardiac glycosides

A
  • Inhibit Na+/K+ ATPase pump
  • Competes with potassium for the external binding site
  • Extremely useful therapeutic tool
44
Q

Clinical significance of Na/K ATPase pump

A
  • Digitalis-based drugs used to treat heart failure
  • Inhibit Na/K ATPase
  • Need to monitor blood potassium levels
  • In hypokalemia, therapeutic dose can become toxic
  • In hyperkalemia, normal dose may be ineffective
45
Q

P-type ATPase

A
  • Pump type
  • Includes Ca-ATPase in plasma and mitochondrial membranes of many cells, sarcoplasmic reticulum of muscle
  • H+-ATPase in many cells particularly acid producing cells of stomach
46
Q

V type ATPase

A
  • Vesicular type

- Actively accumulate hydrogen ion in organelles as lysosomes and storage granules

47
Q

F type ATPase

A
  • Cristae of inner mitochondrial membrane

- The ATP synthase uses the hydrogen gradient to make ATP

48
Q

ABC transporters

A
  • ATP Binding Cassette transporters

- Contain ATP binding sequences that hydrolyze ATP to effect transport

49
Q

Cystic fibrosis transmembrane regulator (CFTR)

A
  • Cl- efflux channel found in hepatic/pancreatic ducts and respiratory passages
  • Can require more than one ATP to be bound for action
50
Q

Mutation of CFTR

A
  • Missing phenylalanine at position 508

- Leads to cystic fibrosis

51
Q

Cystic fibrosis

A
  • Failure to transport Cl-, and therefore Na+ and consequently water into ductular lumen
52
Q

MDR-1 is found in

A
  • Renal tubules

- Intestine

53
Q

MDR-1 function

A
  • Transportation of toxic by-products into the lumen

- Pumps drugs out of cells thereby decreasing their efficacy

54
Q

MDR-1 examples

A
  • Limits anti-retroviral drugs used in AIDS treatment

- Limits anti-neoplastic drugs’ duration of action

55
Q

Secondary active transport

A
  • Active transport across a biological membrane
  • Movement of an ion (typically Na+ or H+) down its electrochemical gradient is linked to the uphill movement of another molecule or ion against its concentration/electrochemical gradient
56
Q

Types of secondary active transport

A
  • Co-transport (symport)
  • Exchange (antiport)
  • Most common type is one involving sodium transport
57
Q

Characteristics of sodium co-transport systems

A
  • Mediated system but much more specific than facilitated diffusion
  • Transported molecule is moved against its concentration gradient
  • Transport is metabolism-dependent but no phosphorylation of the carrier is required
58
Q

3 examples of sodium co-transport systems

A
  • Na+ is required for the transport of glucose across epithelia
  • Sodium is required for the transport of calcium out of cardiac myocytes
  • Hydrogen ion co-transported across intestinal epithelium with di- and tri-peptides
59
Q

When Na+ is required for the transport of glucose across epithelia

A
  • Usually two Na+ ions transported per glucose molecule transported
  • Can take luminal glucose concentrations to very low levels
60
Q

Clinical examples of diseases affecting sodium co-transport system (all rare autosomal recessive diseases)

A
  • Glucose/galactose malabsorption
  • Hartnup’s disease
  • Cystinuria
61
Q

Hartnup’s Disease

A
  • Malabsorption of neutral AA (e.g. Try) in intestine, kidney
62
Q

Cystinuria

A
  • Malabsorption of basic or positively charged AA (Cys, Lys, Orn, Arg) transport in, kidney
63
Q

Other Sodium co-transport systems

A
  • Choline and para-amino hippuric acid (PAH) in kidney and choroid plexus
  • Catecholamine reuptake by neurons
  • Antiport systems, as Na:Ca, Na:H and anion exchange in many membranes as Cl:HCO3
64
Q

Clinical relevance of sodium co-transport systems

A
  • In intestine, coupling of sodium and glucose/amino acid transport explains the rationale of treating cholera with orally administered, balanced salt solutions containing sugars and amino acids
65
Q

Epithelial transport

A
  • Involves two membranes that are polarized (transportation mechanism are different)
  • Net movement through two membranes (transcellular pathway)
66
Q

Epithelial transport movement through two membranes also demonstrates

A
  • Paracellular transport, that is, between cells
67
Q

Exchange diffusion

A
  • 1:1 exchange, no net movement
  • Requires no metabolic energy but shows characteristics of mediated systems
  • May be that antiport system as Na:Ca and Na:H
  • Not 100% specific on internal binding
68
Q

Mediated systems require

A
  • Physical interaction between transporter and transported substance
69
Q

Three types of mediated systems

A
  • Facilitated diffusion
  • Primary active transport
  • Secondary active transport
70
Q

All mediated systems show

A
  • Specificity
  • Competition
  • Saturation characteristics
71
Q

Some mediated systems are passive in which they

A
  • Transport substances down their concentration gradients

- Require no energy

72
Q

Active systems move substances

A
  • Against their concentration gradient
73
Q

Active systems require energy that may be consumed at

A
  • Site of transport

- Distant location

Physiology I: Cellular Neuro (8 decks)

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