'Basic mechanisms of membrane transport is the topic of general pharmacology. Introduction- Membrane Transport Plasma Membrane Lipid solubility in membrane permeation Transporters Versus Channels Mechanisms of Transport Passive Diffusion Relationship between Molecular weight and Diffusion Carrier mediated Transport Facilitated Diffusion Active Transport Primary Active Transport P type- Na+ K+-ATPase Secondary Active transport- Symport, Antiport Intestinal Transporters with e.g Vesicular Transport-Exocytosis, Endocytosis-Phagocytosis,Pinocytosis Pore (Convective) Transport Ion Pair Formation

1. Basic Mechanisms of
Membrane Transport
Presenter-
Akash Agnihotri

2. Introduction- Membrane Transport
 Transportation of molecules through plasma membrane/cell
membrane
 Why we need transport ?
 Cells need Nutrients (Extracellular space)
 Cells need to get away (Toxic materials)
 Membrane transport proteins are present in all organisms
 Which controls – Influx- Essential nutrients & ions
Efflux- Cellular waste, Environmental toxins, drugs &
Xenobiotics etc
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3. Plasma Membrane
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Fluid Mosaic Model (Singer and Nicolson, 1972)
2 Types of pore-
- 10nm
- 50-70nm
Pores provide channel-
Water, ions &
dissolved solutes
(Urea) may move
(Pratt & Tylor 1990)
Hydrophobic tails
Hydrophilic Heads
Phospholipid
Bilayer

4. 4
Lipid solubility in membrane
permeation
Figures The importance of lipid solubility in membrane permeation
Lipid solubility Membrane concentration CM

5. Transporters Versus Channels
Channels
 In general, channels have two primary states, open and closed
 In open state- act as pores for selected ions (electrochemical
gradient)
 After opening, channels return to closed state as a function of
time
 Drugs termed potentiators (e.g., ivacaftor) may increase
probability that a channel is in open state
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6. Transporters Versus Channels
Transporters
 Transporter- forms intermediate complex with substrate (solute)
 Subsequent conformational change in transporter
 Induces translocation of substrate to other side of membrane
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7. Transporters Versus Channels
 Kinetics of solute movement differ between transporters and
channels
 Particular transporter forms intermediate complexes with
specific compounds (Substrates)
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8. Mechanisms of Transport
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Passive
Diffusion
Carrier
mediated
Transport Vesicular
Transport
Pore
(Convective)
Transport Ion Pair
Formation
• Facilitated Diffusion
• Active Transport
• Primary
• Secondary
• Carrier mediated
intestinal Transport
• Pinocytosis
• Phagocytosis
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2
3
4
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9. 1. Passive Diffusion
 Nonionic diffusion (90% drugs)
 Molecules spontaneously diffuse from a region of higher
concentration to a lower concentration
 Driving force- Solute’s Concentration (Electrochemical) gradient
 No external energy is required
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Rate of Transfer= Flux

10. Passive Diffusion
 Best Expressed by- Fick’s law of diffusion (Adolf Fick)
 According to law- Drug molecules diffuse from a region of high
drug concentration to a region of low drug concentration
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dQ
dt
=
DAK
h
(CGI - Cp)
Surface area (A) Diffusion rate Thickness(h) Diffusion rate

11. Relationship between Molecular
weight and Diffusion
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Molecular Weight Diffusion

12. 2. Carrier mediated Transport
 Cell membranes possess specialised transport mechanisms
 Regulate entry and exit of physiologically important molecules
 Sugars, amino acids, neurotransmitters and metal ions
 Lipid soluble + Low molecular weight compound readily
crosses membrane
 Suggest- presence of specialized transport mechanism
 Component of membrane called as Carrier
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13. Carrier mediated Transport- Mechanism
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• Carrier binds reversibly with solute molecule
• Made complex
• Travel across membrane to other side
• Dissociated and discharge drug
• Carrier return to its original site

14. CMT- Facilitated Diffusion
 Facilitated diffusion is a form of transporter-mediated
membrane transport
 Does not require energy (Just as in passive diffusion)
 Saturable and structurally selective for drugs
 Shows competition kinetics for drugs of similar structure
 So, minor role in drug absorption
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15. CMT- Facilitated Diffusion
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• Both result in a final equilibrium distribution of a solute across
membrane
• Facilitated diffusion employs a specific transporter and exhibits
Michaelise Menten saturation kinetics

16. Active Transport
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 Drug transported from a region of lower to one of higher
concentration
 Against concentration gradient
 Uphill transport (Energy is required)
 Can be inhibited by metabolic poisoning that interfere with
energy production (e.g, Fluoride, cyanide and dinitrophenol)
 5-fluorouracil (Lipid insoluble drug)- Absorbed by GI

17. Active transport
 Depending on the driving force, divided into 2 types
 Primary active transport
 Secondary active transport
 Symport
 Antiport
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18. Primary Active Transport
 Direct active transport or uniport
 ATP hydrolysis is coupled directly to solute transport
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Low conc.
High conc.
It involves using energy (usually ATP) to directly pump a solute across a membrane
against its electrochemical gradient.

19. Primary Active Transport
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20. P type- Na+ K+-ATPase
 Most important active transport protein
 This single enzyme accounts for one-third of human energy
expenditure and is often referred to as the “pacemaker for
metabolism.”
 Enzyme discovered in 1957 by Jens Skou (Nobel prize in
chemistry, 1997)
 Na+ K+-ATPase is inhibited by digoxin, a cardiac glycoside
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21. Secondary Active transport
 Also known as cotransport
 Transport across a biological membrane of solute against its
concentration gradient is energetically driven by transport of
another solute in accordance with its electrochemical gradient
 2 types depending on transport direction of solute-
 Symporters or Antiporters
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22. Secondary Active transport
 Ion gradient is coupled to movement
of a solute in either:
 Same direction (symport)
 Opposite direction (antiport)
 Purpose of both types of co-
transport is to use energy in an
electrochemical gradient to drive the
movement of another solute against
its gradient
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23. Secondary Active transport- Symport
Example
 SGLT1 (sodium-glucose transport protein-
1) in intestinal epithelium
 Transport S2 and S1 in the same
direction, as for glucose transport into the
body from the lumen of the small intestine
by the Na+-glucose transporter SGLT1
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24. Secondary Active transport- Antiport
Example
 Transporter moves S2 and S1 in opposite
directions
 Using inwardly directed Na+ concentration
gradient across the plasma membrane that
the Na+,K+-ATPase maintains, the inward
movement of 3 Na+ can drive the outward
movement of 1 Ca++ via the Na+/Ca++
exchanger
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25. Intestinal Transporters with e.g
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26. 3. Vesicular Transport
 Process of engulfing particles or dissolved materials by cells to
form a saccule or vesicle (This vesicles also called corpuscular
or vesicular transport)
 2 Process involved-
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Cells excrete
waste and
other large
molecules
Vesicular
Transported
of solute

27. Vesicular Transport- Exocytosis
Example
 Transport of protein such as insulin
 Insulin molecules are first packaged into intracellular vesicles
then fuse with plasma membrane to release insulin outside the
cell
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28. Vesicular transport- Endocytosis
 2 Types of
endocytosis-
 Phagocytosis
 Pinocytosis
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Fig- Cells excrete waste and other large
molecules

29. Endocytosis- Phagocytosis
 Cell eating
 Uptake of large solid particles,
often >0.5 mm
 Has surface proteins that
specifically recognize and bind
to the solid particles
 Phagocytosis is a routine
process that ameba and ciliated
protozoa use to obtain food
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30. Endocytosis- Pinocytosis
 Cell drinking
 In humans, this process occurs in cells lining the small
intestine and is used primarily for absorption of fat droplets
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31. 4. Pore (Convective) Transport
 Very small molecules (Urea, water & sugars) are able to cross
cell membrane rapidly if membrane contained channels or
pores
 A certain type of protein called a transport protein may form an
open channel across the lipid membrane of cell
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32. 5. Ion Pair Formation
 Absorption of drugs like Quaternary ammonium compounds and sulfonic
acids (Highly ionized or charged particles)
 Propranolol forms ion complex with oleic acid
 Quinine with hexylsalicylate
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33. Ion Pair Formation- types
 2 basic types of ion pairing (ionophores)
 Channel former
 Mobile former
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34. Summary
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35. References
 Goodman LS. Goodman and Gilman's the pharmacological basis of
therapeutics. New York: McGraw-Hill; 2018.
 Shargel L, Andrew BC, Wu-Pong S. Applied biopharmaceutics &
pharmacokinetics. Stamford: Appleton & Lange; 2005.
 Stillwell W. Membrane transport. An Introduction to Biological
Membranes. 2013:305. https://dx.doi.org/10.1016%2FB978-0-444-
52153-8.00014-3.
 Flower RJ, Henderson G, Loke YK, MacEwan D, Rang HP. Rang &
Dale's Pharmacology E-Book. Elsevier Health Sciences; 2018 Nov 4.
 Brahmankar DM, Jaiswal SB. Biopharmaceutics and pharmacokinetics: A
treatise. Vallabh prakashan; 2005.
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36. Thank you
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