Membrane structure and transport for medical school Biochemistry

1. MEMBRANES:
STRUCTURE & TRANSPORT
V.S.RAVIKIRAN, MSc.

2. V.S.RAVIKIRAN, MSc.,
Department of Biochemistry,
ASRAM Medical college,
Eluru-534005.AP, India.
vsravikiran2013@gmail.com

3. MEMBRANES:
STRUCTURE & TRANSPORT

5. 1. A physical barrier to separate
the inside and outside of the
cells.
2. Biological membrane consists of
lipids, proteins and
carbohydrates.
3. How do they come together to
form a self-organized
membrane? E.g. Membrane
proteins: how do they get there?
1. Membranes: Functions, Structures,
Properties, and Membrane Proteins
http://en.wikipedia.org/wiki/Cell_membrane
THE FLUID_MOSAIC MODEL OF PLASMA
MEMBRANE

6. Functions of Cell Membrane are to:
1. regulate cell volume
(control water in/ out)
2. maintain intracellular pH
(H+ regulation)
3. selectively regulate ionic
composition (e.g. Na+ , K+ )
4. concentrate metabolic fuel
(nutrients, ATP, etc)
,

7. Membrane transport system ought to (continued):
5. concentrate and move building blocks (amino
acids, etc)
6. remove toxic compounds (detoxification, trap
and/or pump out)
7. generate ionic gradients to maintain excitability
of nerve and muscle cells
8. control the flow of “information” within the cell,
between cells and their environment.

8. Functions and properties of membrane
• Membrane is a selectively permeable barrier
between the cell and the external environment.
• Its function is to maintain Homeostasis. Its
selective permeability allows the cell to maintain a
constant internal environment.
• Plasma membranes form compartments
(compartmentation) within cells.

9. Fig 7.3 Fluid Mosaic Model for
Membrane
• 1972 SJ Singer and G Nicolson
Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings
membrane proteins are
dispersed and individually
inserted into the
membrane

10. Cell Membrane

11. Fig 7.7 Animal Cell Plasma Membrane

12. 1.5 The Fluid-Mosaic Model
(Singer and Nicolson, 1972):
1. Amphipathic lipids stabilized by the hydrophobic interaction
form the lipid bilayer .
2. Asymmetric property. The components of membranes with
lipids and proteins are asymmetrically oriented: the two faces
are different.

13. 4. It is a fluid-like structure, with fluidity regulated by the
number of double bonds in the fatty acids (increasing
unsaturation increases fluidity) and cholesterol content
(increasing cholesterol decreases fluidity).

14. Rotation - spins about its axis
Flexion - FA tails “wag” back and forth
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fluidity of membranes: Lateral movement. Proteins and the
components are free to move laterally, no or little flip-flopping allowed
(flippase or transporter is needed.
and rapid

15. Fatty acids and phospholipids
• Membranes have 3 kinds of lipids:
phospholipids, glycolipids, & cholesterol
• Fatty acids (FAs) form the basic structures of
phospholipids & glycolipids
• Saturated FAs VS Unsaturated FAs
• Strong van der waals interaction between the
non-polar hydrocarbon regions of the molecules

16. Three views of the same molecule

17. Fatty acids (FAs) form the
basic structures of
phospholipids
1.2.1 Simplified structure of lipid bilayer and phospholipids
Polar group
Phosphate
Glycerol
Fatty acid-
(unsaturated)
Phospholipid molecule
Fatty acid (saturated)
Hydrophilic
head
Hydrophobic
fatty acid
tails
Hydrophobiccore
oflipidbilayer
Hydrophilic head to cytoplasm
Hydrophilic
head on
surface

18. 1.2.2 Basic structure of fatty acid
chains: saturated and unsaturated.
Hydrophilic carboxyl end
Hydrophobic hydrocarbon (alipathic) tail
Forming an amphipathic molecule
Adapted from Alberts et al., 1998. Essential Cell
Biology. An Introduction to Molecular Biology of
the Cell. Garland Pub.Inc.
Saturated Fatty
Acids
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
C
OHO
CH2
CH2

19. Characteristics of Plasma membranes
• Membranes are held up with
van der Waal’s force with no
covalent interactions among
molecules, therefore they can
fuse together.
• Hydrophobic interaction also
help stabilization membrane
bilayer.
• Heat promotes lipid bilayer
from gel (crystalline) state to
fluid state. http://en.wikipedia.org/wiki/Cell_membrane
Explain why and how a detergent can kill germs?? Why bleach
and alcohol can kill bacteria and viruses??

20. • Membrane processes like budding, exo- and endo-
cytosis are common events.
• By membrane fusion, Golgi complex and move
proteins to vesicles and surface membrane. Secretary
proteins are stored in the vesicles, their membranes
can fuse to the plasma membranes to excrete the
secretory proteins with exocytosis.
• The mitochondrion has 2 layers of membrane, the
inner is similar to their descendant of prokaryotes, the
outer from eukaryotes; indicating its symbiotic origin.

21. Asymmetry of plasma membranes
1. Membrane separates interior and exterior side of the
cell and the 2 faces of lipid bilayer are different in
composition and structure, with different proteins and
phospholipids.
2. The plasma membrane core contain 1/3 cholesterol
and 2/3 phospholipids and sphingolipids, the outer
leaflet contains 5% glycolipids.

22. Asymmetry of plasma membranes
2. Oligosaccharide chains
are attached at outer
face of lipids or proteins.
3. Shingomyelin and
phosphatidylcholine are
mainly at the outer face
of the bilayer.
4. Phosphotidyl-
ethanolamine and
phosphatidylserine are
mainly in the inner face.

23. Lipid composition of different plasma membranes: note cholesterol
contents

24. Cholesterol stays in between fatty acids with its
rigid planar steroid ring
Phosphate
Glycerol
Fatty acid-
(unsaturated)
Hydrophobic
fatty acid
tails
Polar Head
Rigid
Planar
Steroid
Ring
Polar Head
Non polar
hydrocarbon
Tail
Cholesterol is a metabolic
precursor of steroid hormones;
it is a member of steroids or
lipids and major component of
animal plasma membrane.

25. Cholesterol contents
• Plasma membrane= 25-30%
• Nuclear membrane= 10%
• Golgi/R.E.R.= 6 - 7%
• Mitochondria: outer= 4 -5%, inner= 2 -5%

26. Cholesterol contents
• Bacterial cells do not have cholesterol, whereas in
animal cells, cholesterol is a key regulator of
membrane fluidity.
• It makes bilayer less fluid (reduce fluidity), but it also
prevent hydrocarbon chains come together to
crystallize. It inhibits phase transitions.

27. 4-27
Fluid-mosaic model

28. • Proteins - may be peripheral proteins or
integral proteins.

29. • Ion channel
• Transporter
• Receptor
• Enzyme
• Cell Identity marker
• Linker

30. 30
Membrane Proteins
Membrane proteins have various functions:
1. transporters
2. enzymes
3. cell surface receptors
4. cell surface identity markers
5. cell-to-cell adhesion proteins
6. attachments to the cytoskeleton

31. 31

32. 4-32
• Other Components
• 1) Proteins - may be peripheral proteins or
integral proteins.
• 2) Glycolipids - phospholipids with
carbohydrate chains attached
• 3) Glycoproteins -proteins have
carbohydrate chains attached.
• The carbohydrate chains of 2) and 3) form
the glycocalyx

33. 4-33
• Functions of the Glycocalyx
1) cell-to-cell recognition
2) cell-cell adhesion
3) reception of signal molecules.
• The diversity of carbohydrate chains is
enormous, providing each individual with a
unique cellular “fingerprint”.

34. The Modes of Membrane
Transport

35. Lipid bilayer
Small hydrophobic molecules: O2,
CO2, N2, benzene
Small uncharged polar molecules: H2O,
ethanol, glycerol
Larger uncharged polar molecules:
glucose, amino acid, nucleotides
Plasma membrane is a semi-permeable (selective)
membrane
Ions: H+, Na+, HCO3
- , K+, Ca+,
Mg2+, CL- , etc. Transporters or
channels
The process of diffusion of water is called osmosis.
But why some can diffuse while some cannot? What criteria are controlling the diffusion of
molecules across the membrane ?

37. Passive transport: facilitated diffusion for all channel protein
and part of carrier (concentration or electrochemical gradient)
Active transport: against electrochemical gradient; mediated
by carrier (pump); use ATP or ion gradient as energy source

38. DIFFUSION (hydrophobic/
lipophilic molecules only):
a slow process.
FACILITATED DIFFUSION,
uniport (e.g. glucose transporters)
CO-TRANSPORT: symport
(same direction) or antiport
(opposite directions
ACTIVE TRANSPORTER,
against the concentration gradient
CHANNELS, e.g. sodium channel,
water channel (aquaporin)
1. Overview of transport mechanisms
ATP
ADP + Pi

39. Passive Transport
Diffusion Simple (Passive)Diffusion
no carriers is involved
 tendency of molecules to spread out into the
available space
 driven by the kinetic energy (heat) of the
molecules
 random motion of individual molecules, but
movement of a population may be directional

40. High concentration to low concentration until conc. is equal
Movement down a concentration gradient.
Diffusion of solutes across
membranes
High LowHigh Low
Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

41. High concentration to low concentration until conc. is equal
Movement down a concentration gradient
Fig 7.11b Diffusion of two
solutes
- each diffuses independently
Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

42. •Molecules that are
transported through the cell
membrane via simple diffusion
include organic molecules,
such as benzene and small
uncharged molecules, such as
H2O, O2, N2, urea, glycerol, and
CO2
Gas exchange in lungs by diffusion

43. 4-43
Facilitated diffusion Passive transport (facilitated
diffusion)
energy independent, down the concentration gradient
1)follows
concentration
gradient
2)requires carrier
protein
3)often for large or
charged molecules
4)can be regulated

44. 4-44
Transport by Carrier Proteins
 Carrier proteins -specific and combine with
only a certain type of molecule.
 Functions
1) Facilitated Diffusion –follows concentration
gradient, requires carrier protein, often for
large or charged molecules, can be regulated
2) Active Transport –against concentration
gradient, requires energy, requires carrier
protein, can be regulated

45. Two classes of transfer protein:
(1) Carrier protein (permease, transporter,
pump) : for specific molecule; usually
coupled with energy source
(2) Channel protein: inorganic ions; down to its
concentration gradient; fast
overall, transfer proteins create electrical
(because of membrane potential) and
concentration gradient, in turn, used as a
driving force (electrochemical gradient) to
facilitate the transport process

46. Electrochemical gradient combines with
membrane potential as a driving force

47. Involved conformation change
Both carrier and channel
contain specialized
transmembrane domain
Transport through channel: fast transport

48. • Protein or carrier-mediated
• Characterized by saturation kinetics
• much faster than simple diffusion
• Facilitators have chemical and
stereochemical specificity for transported
molecules (for example, glucose
transporter would transport D-glucose, but
not L-glucose, valinomycin transport K+
ions 20,000 times better than Na+)
• susceptible to competitive inhibition
Facilitated diffusion - transport of molecules in an energy-independent
fashion down the electrochemical gradient

49. Kinetics of simple diffusion and carrier-mediated
diffusion (expressed as Vmax/Km or Bmax/Kd)

50. Model of Carrier protein: passive transport

51. Transport Proteins: Facilitated
Diffusion Via Carrier Proteins
• Molecule causes a controlled denaturation resulting
in a molecule being transported
• May be specific
• May be saturated or inhibited
• Protein assists the process of diffusion; passive
mechanism

52. Passive-Mediated Glucose Transport
facilitates glucose uptake about 50,000 fold
• Erythrocytes glucose transporter is a 55 kDa glycoprotein with 12
transmembrane segments
• The transporter is believed to function through “alternating conformation”
mechanism
• Transport can occur in either direction and serves mainly to equilibrate
glucose concentration

53. Three types of carrier-mediated transport: uniport, symport
( kidney/GI epitghelial cells ) and antiport (determined by its
path direction)

54. Classes of
carrier
proteins
Uniport (facilitated diffusion) carriers mediate
transport of a single solute.
An example is the GLUT1 glucose carrier.
The ionophore valinomycin is also a uniport carrier.
Uniport Symport Antiport
A A B A
B

55. A gradient of one substrate, usually an ion, may drive uphill
(against the gradient) transport of a co-substrate.
It is sometimes referred to as secondary active transport.
E.g:  glucose-Na+ symport, in plasma membranes
of some epithelial cells
 bacterial lactose permease, a H+ symport carrier.
Uniport Symport An
A A B
Symport (cotransport) carriers
bind two dissimilar solutes
(substrates) & transport them
together across a membrane.
Transport of the two solutes is
obligatorily coupled.

56. A substrate binds & is transported.
Then another substrate binds & is transported in the
other direction.
 Only exchange is catalyzed, not net transport.
The carrier protein cannot undergo the conformational
transition in the absence of bound substrate.
Antiport (exchange diffusion) carriers
exchange one solute for another across a
membrane.
 Usually antiporters exhibit "ping pong"
kinetics.
Uniport Symport Antiport
A A B A
B

60. Example of an antiport carrier:
Adenine nucleotide translocase (ADP/ATP exchanger)
catalyzes 1:1 exchange of ADP for ATP across the inner
mitochondrial membrane.
ATP 4

ADP 3
mitochondrial
matrix
adenine nucleotide translocase

61. Ionophores: small hydrophobic molecules (originally
formed by microorganism) in membrane to transport
specific ions; not coupled to energy source (down to
concentration gradient)
1. Valinomycin: potassium ion (mobile)
2. FCCP: hydrogen ion (mobile)
3. A23187: calcium and magnesium ion (mobile)
4. Gramicidin A: monovalent cation (channel former)

62. Osmosis
• Direction of osmosis is determined only by a
difference in total solute concentration
– kinds of solutes in the solutions do not matter
• What happens to cells in hypertonic,
hypotonic, and isotonic solutions?
– cytoplasm vs. solution cells are in

63. Passive Transport of Water -
Osmosis
• Terms to define comparisons of solute
concentrations in solutions
– Hypertonic
• the solution with the higher concentration of solutes
– Hypotonic
• the solution with the lower concentration of solutes
– Isotonic
• solutions with equal solute concentrations

64. Isotonic
Fig 7.12 Osmosis - passive transport of water
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

65. Fig 7.12
Osmosis
Copyright © 2005 Pearson Education, Inc.,
publishing as Benjamin Cummings

66. Fig 7.13 The water balance of living
cells
(wilts) (lethal)
Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

67. Ion channels: channels mediate inorganic ion transport
1. Narrow, highly selective pores that can open and close
2. Approximately 100 million ions can pass through / second
(105 times greater as compared to any carrier)
3. Can not couple to energy source to perform active
transport (always passive – downhill)
4. They are gated (open and close status); prolong stimulation
would desensitized or inactivated ( closed; usually through
phorphorylation)
5. All animal cells contain ion channels, not limited to neuron;
each neuron might have more than 10 types of channel

68. Ion channels open in response to special stimulus

69. Ligand-gated ion channels
• Mediate rapid action of neurotransmitters
at synapse by changing the potential of the
membrane in response to neurotransmitter
(ligand) binding
• selectively activated by specific ligand
• discriminate between negatively and
positively charged ions, but otherwise are
not strongly selective
Cation-conducting channels - acetylcholine-,
serotonin- and glutamate receptors
Anion-conducting channels - glycine and g-
aminobutiric (GABA) acid -gated receptors

71. Active transport
- energy-dependent, against concentration
gradient

72. 4-72
Active transport
1) against concentration gradient
2) requires energy (ATP)
3) requires carrier protein
4) can be regulated

73. Primary Active Transport - utilizes energy of ATP hydrolysis
–P-type ATPases (Na,K-ATPase,
H,K-ATPases, Ca-ATPase,
Zn2+/Pb2+transporting ATPase of
bacteria)
–V-type ATPases and F1F0-ATPases
(Na+-ATPase and H+-ATPase)
–ATPases that transport peptides
and drugs (multidrug-resistance
protein, P-glycoprotein, yeast a-
factor transporter

74. Greatest consumer cellular energy
Sets up concentration & electrical gradients
Hydrolysis of 1 ATP moves 2K+ in and 3Na+ out against
their concentration gradients
Na+/ K+ ATPase
Na,K-ATPase is a receptor of digitalis and related cardiac
glycosides used to strengthen the heartbeat

75. Mader: Biology 8th Ed.

76. Ca2+-ATPase of Sarcoplasmic Reticulum
• Plays a major role in muscle relaxation
by transporting released Ca back into SR
• A single subunit protein with 10
transmembrane fragments
• Is highly homologous to Na,K-ATPase

78. Secondary Active (Coupled) Transport - utilizes
ion-gradients generated by primary transporters

79. Types of Secondary Transporters
– Symporters (two solutes
move in same direction)
Lac- permease,
Na+/glucose transporter)
– Antiporters (two solutes
move in opposite directions
Na+/Ca2+ exchanger)
– Uniporters (mitochondrial
Ca2+ uniporter and NH+
4-
transporter in plants require
H+ gradient)

80. 4-80
Exocytosis and Endocytosis
• exocytosis -vesicles fuse with the plasma
membrane for secretion.
• Examples -release of digestive enzymes,
secretion of insulin

81. 4-81
Exocytosis

82. AS Biology, Cell membranes and Transport 82
Vesicle-mediated transport
Vesicles and vacuoles that fuse with the cell membrane may be utilized to
release or transport chemicals out of the cell or to allow them to enter a cell.
Exocytosis is the term applied when transport is out of the cell.

83. 4-83
Endocytosis
• Endocytosis -cells fold membrane around
substances and bring them into the cytoplasm
(form a vesicle)
• Endocytosis occurs as:
• Phagocytosis – large particles
• Pinocytosis – small particles
• Receptor-mediated endocytosis – specific
particles

84. Endocytosis

85. Phagocytosis

86. 4-86
Phagocytosis
(large particles)

87. 4-87
Pinocytosis
(small particles)

88. 4-88
Receptor-mediated endocytosis
(specific molecules)

89. AS Biology, Cell membranes and Transport 89
Cell Membrane - Function - Endocytosis
The cell membrane can also engulf structures that are much too large to fit through the pores in
the membrane proteins this process is known as endocytosis. In this process the membrane itself
wraps around the particle and pinches off a vesicle inside the cell. In this animation an ameba
engulfs a food particle.

90. Transcellular transporter: apical to basolateral transport
nutrients (intestinal epithelial cells: microvilli)
Ex., - Ig A, transferrin, insulin

91. CLINICAL APPLICATIONS
Membrane Transport and Human
Disease

92. Membrane Transport and Human Disease
 Hartnup’s disease
 Cystinuria
 Vitamin D resistant rickets
 Nephrogenic diabetes insipidus (NDI) [renal AQP2],
acquired hypokalemia and hypercalcemia

93. Clinical applications of channels
 Liddle’s disease, the sodium channels in
the renal epithelium are mutated, resulting
in excessive sodium reabsorption, water
retention and elevated blood pressure.

94. “Long QT syndrome”
 Potassium channel mutations in “Long
QT syndrome” leads to inherited cardiac
arrhythmia, where repolarization of the
ventricle is delayed, resulting in prolonged
QT intervals in ECG.

95. “Long QT syndrome”
 Potassium channel blockers are used in
cardiac arrhythmias.
 Potassium channel openers as smooth
muscle dilators.

96. Chloride channel
 The role of GABA and glycine as inhibitory
neurotransmitters is attributed to their
ability to open the chloride channels at the
postsynaptic membranes.

97. Bartter syndrome
 Bartter syndrome is due to mutations in
potassium and chloride channels in the
renal tubules, especially the ascending
limb.
 The condition is characterized by
hypokalemia and alkalosis and loss of
chloride and potassium in urine.

98. Calcium channel
 Calcium channel blockers are used in the
treatment of hypertension.

99. 5. Active transporters
 P-type: Na+-K+-ATPase, Ca2+ and H+ pump, P means
they have phosphorylation and they all sensitive to
vanadate inhibition.
 V-type: inner membrane ATPase to regulate H+ and
adjust proton gradients, v means vacuole type for
acidification of lysosomes, endosomes, golgi, and
secretory vesicles.
 F-type: ATP synthase to generate ATP energy from
moving the proton across; F means energy coupling
factor. There are F1 and F0 subcomplexes: F1 generates
ATP, F0 lets H+ go through the membrane.
 ABC transporters: ATP-binding cassette protein for
active transport of hydrophobic chemicals and Cl-.
5. Active transporters
Classified according to their protein
sequence homology and structures.

100. ATP-dependent ion pumps are grouped into classes
based on transport mechanism, as well as genetic &
structural homology.
Examples include:
 P-class pumps Na+,K+-ATPase, (H+, K+)-ATPase,
Ca++-ATPases
 F-class (e.g., F1Fo-ATPase)
& related V-class pumps.
ABC (ATP binding cassette) transporters, which
catalyze transmembrane movements of various organic
compounds including amphipathic lipids and drugs.

101. Menkes and Wilson Diseases are caused
by mutated copper ion transporters
 Copper ion transporters (ATP 7A and 7B) are
essential to homeostasis of copper contents in our
body.
 Menkes disease: copper gets into the intestine
but cannot transport further (mutated ATP7A),
leading to copper deficiency. Copper histidine is
needed for infiltration treatment.
 Wilsons disease: copper in the liver cannot get
into ceruloplasmin to excrete (mutated ATP7B),
leading to copper accumulation in kidney, brain,
and cornea. Penicillamine is needed for treatment
to remove excessive copper, with zinc supplement.

102. Wilson’s disease protein (ATP7B) is a key regulator of copper
concentration in the liver
Normal liver
ATP7B -/- liver

103. Genetic defects of CFTR
leads to CF (Cystic fibrosis).
CF is the most common
genetic diseases in
Caucasians (1/1000). Cell
death in the lung’s
epithelial due to lack of ion
control, leading to
malfunction of cells with
mucus obstruction of gas
exchanges and thus lethal
to juveniles having CF.
Adapted from Sperlakis (ed)., 1998. Cell
Physiology Source Book. Academic Press.
G
AC
ATP
ATP
cAMP
ADP
Agonist
MembraneRe
ceptor
PKAa
PKAj
CFTR-Cl channel is an ATP- and cAMP
dependent Cl channel on epithelial cell
membrane.
CFTR and Cystic
Fibrosis
5. Active transporters

104. • Cystic Fibrosis and CFTR (the most common fatal
childhood disease in Caucasian populations). Inadequate
secretion of pancreatic enzymes leading to nutritional
deficiencies, bacterial infections of the lung and
respiratory failure, male infertility.
• Bile Salt Transport Disorders Several ABC transporters,
specifically expressed in the liver, have a role in the
secretion of components of the bile, and are responsible
for several forms of progressive familial intrahepatic
cholestasis, that leads to liver cirrhosis and failure.
Membrane Transport and Human Disease

105. Membrane Transport and Human Disease
• Retinal Degeneration The ABCA4 gene produts transports
retinol (vitamin A) derivatives from the photoreceptor outer
segment disks into the cytoplasm. A loss of ABCA4 function
leads to retinitis pigmentosa and to macular dystrophy with
the loss of central vision.
• Mitochondrial Iron Homeostasis ABCB7 has been implicated
in mitochondrial iron homeostasis. Two distinct missense
mutations in ABCB7 are associated with the X-linked
sideroblastic anemia and ataxia
• Multidrug Resistance ABC genes have an important role in
MDR and at least six different ABC transporters are associated
with drug transport

106. Ouabains for treatments of angina pectoris
and myocardial infarction
• Ouabain blocks Na + -K + -ATPase. By blocking
the Na+-K+-ATPase, Intracellular Na+ remains
high
• Hence, the Na+- Ca2+ antiport cannot remove
Ca2+ ions out from the cardiac muscle cells.
• Eventually, the Ca2+ ion level is restored to
maintain the contraction power of cardiac muscle.

107. Anion antiport in parietal cells of stomach with H+- K+ -
ATPase to produce stomach acid.
Basolateral
membrane
Apical membrane
CO2
CO2
HCO3
Carbonic
anhydrase
Cl - Cl -
Cl -
HCO3
K+
K+
K+ channel
Anion antiport
Cl -channel
H+-K+-
ATPase
ATP
ADP + Pi
K+
H2O
+ OH -
Omeprazole
inhibits the
proton pump.

108. Omeprazole and Cimetidine stop
stomach acid
• H+-K+-ATPase is an electroneutral antiport. K+ is
removed by K+ channel and concurrently Cl-
channel removes Cl- to the same direction.
• HCl is the overall transport product in the stomach
lumen.
• Omeprazole inhibits the proton pump directly.
• Cimetidine resembles histamine to block the
binding of histamine to its receptor thus inhibit the
activation of H+K+-ATPase by histamine receptor.

109. THE END
THANKS FOR YOUR
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