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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
Systems can be inhibited by specific poisons such as
- HgCl2 | - Dinitrofluorobenzene
26
Systems are not affected by non-specific metabolic poisons such as
- Cyanide | - Dinitrophenol
27
Examples of facilitated diffusion
- Sugars | - Urea
28
Sugars (facilitated diffusion) diffuse into
- RBC - WBC - Myocytes - Adipocytes - Choroid plexus
29
Large family of transporters for sugars include
- GLUT (14 members currently) | - One of which is insulin dependent (GLUT 4)
30
Insulin increases rate of glucose transport in
- Myocytes | - Adipocytes
31
Urea (facilitated diffusion) found in
- Collecting duct of nephrons | - Transport urea out of duct
32
Amino acids (facilitated diffusion) diffuse into
- RBC & WBC - Out of intestinal epithelium - Wide variety of systems - At least 3 basic types
33
Active transport
- Moves atoms, ions, molecules against a concentration gradient - Helps maintain concentration differences across permeable barriers
34
In active transport,
- Work must be done - Energy (ATP) is required - Directly in primary active transport - Secondarily in secondary active transport
35
Active transport shares
- All the characteristics of mediated transport systems
36
Primary active transport energy consumption
- 1/3 total resting energy (ATP) consumption of humans is used in pumping these ions
37
In primary active transport, gradients control
- Cell volume - Membrane excitability - Drive sodium cotransport of sugars/amino acids/nutrients
38
Concentration gradients in primary active transport are maintained by
- Na+/K+ ATPase | - Located in the plasma membrane
39
Intracellularly, most cells have a _____ concentration of K+ and a _____ concentration of Na+
- High [K+] | - Low [Na+]
40
Model of Na+/K+ ATPase
- 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
Na+/K+ ATPase is electrogenic
- Generates an electrical current in the plasma membrane
42
Na+/K+ ATPase pump can be reversed
- To synthesize ATP
43
Cardiac glycosides
- Inhibit Na+/K+ ATPase pump - Competes with potassium for the external binding site - Extremely useful therapeutic tool
44
Clinical significance of Na/K ATPase pump
- 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
P-type ATPase
- 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
V type ATPase
- Vesicular type | - Actively accumulate hydrogen ion in organelles as lysosomes and storage granules
47
F type ATPase
- Cristae of inner mitochondrial membrane | - The ATP synthase uses the hydrogen gradient to make ATP
48
ABC transporters
- ATP Binding Cassette transporters | - Contain ATP binding sequences that hydrolyze ATP to effect transport
49
Cystic fibrosis transmembrane regulator (CFTR)
- Cl- efflux channel found in hepatic/pancreatic ducts and respiratory passages - Can require more than one ATP to be bound for action
50
Mutation of CFTR
- Missing phenylalanine at position 508 | - Leads to cystic fibrosis
51
Cystic fibrosis
- Failure to transport Cl-, and therefore Na+ and consequently water into ductular lumen
52
MDR-1 is found in
- Renal tubules | - Intestine
53
MDR-1 function
- Transportation of toxic by-products into the lumen | - Pumps drugs out of cells thereby decreasing their efficacy
54
MDR-1 examples
- Limits anti-retroviral drugs used in AIDS treatment | - Limits anti-neoplastic drugs’ duration of action
55
Secondary active transport
- 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
Types of secondary active transport
- Co-transport (symport) - Exchange (antiport) - Most common type is one involving sodium transport
57
Characteristics of sodium co-transport systems
- 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
3 examples of sodium co-transport systems
- 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
When Na+ is required for the transport of glucose across epithelia
- Usually two Na+ ions transported per glucose molecule transported - Can take luminal glucose concentrations to very low levels
60
Clinical examples of diseases affecting sodium co-transport system (all rare autosomal recessive diseases)
- Glucose/galactose malabsorption - Hartnup's disease - Cystinuria
61
Hartnup's Disease
- Malabsorption of neutral AA (e.g. Try) in intestine, kidney
62
Cystinuria
- Malabsorption of basic or positively charged AA (Cys, Lys, Orn, Arg) transport in, kidney
63
Other Sodium co-transport systems
- 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
Clinical relevance of sodium co-transport systems
- 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
Epithelial transport
- Involves two membranes that are polarized (transportation mechanism are different) - Net movement through two membranes (transcellular pathway)
66
Epithelial transport movement through two membranes also demonstrates
- Paracellular transport, that is, between cells
67
Exchange diffusion
- 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
Mediated systems require
- Physical interaction between transporter and transported substance
69
Three types of mediated systems
- Facilitated diffusion - Primary active transport - Secondary active transport
70
All mediated systems show
- Specificity - Competition - Saturation characteristics
71
Some mediated systems are passive in which they
- Transport substances down their concentration gradients | - Require no energy
72
Active systems move substances
- Against their concentration gradient
73
Active systems require energy that may be consumed at
- Site of transport | - Distant location

Physiology I: Cellular Neuro (8 decks)

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