1. Transport across the membrane
Dr.DHARAMBIR
M.D.3rd year
SGT Uni. Gurugram

2. • Transport of various small and large molecules
across the cell membrane, which is relatively
impermeable, occurs by several mechanisms.
• Transport of small molecules
• Passive transport
• Diffusion
• Facilitated diffusion. By transporters
By ion channels

5. Transport of large molecules
• By endocytosis
• By exocytosis
• Beside the above, cell membrane is also
involved in signal transduction across the
membrane via receptors and signal
internalization.
.

6. • Passive transport-Without the input of any
energy,occurs under the influence of
concentration gradient
• Facilitated transport-It is also a passive
transport but it uses specific transport proteins
called carriers.
• Active transport-Occurs against a
concentration gradient and requires the input
of energy as ATP.

8. Membrane transporter
• Transporter are involved in facilitated as well
as active transport of solute.
• Uniport-Transport one type of molecule
bidirectionally
• Symport-Transport two types of molecules in
same direction.e.g. Na+ glu.symport
• Antiport-Transport two different molecules in
the opposite direction.e.g. Na+-Ca++

11. Property of a Transporter
• A specific solute binding site
• A saturable system and has a maximum rate of
transport (Vmax).
• An affinity towards the solute (Km) like
enzymes.
• Transporters are different in one important
aspect from enzyme.They do not modify the
solute unlike enzymes which convert the
substrate into product.

13. • Diffusion-Simple diffusion occurs the con.
gradient and its solublity in the hydrophobic
membrane core of the membrane
• Gases co2 and o2 diffuse freely.
• Na+,k+,Cl-,which are poorly soluble in lipid
do not diffuse easily. They require hydration
shell,the size of which is directly proportional
to charge density on ion.
• Na+ has higher charge,large shell of water,
diffuse slowly than K+.

14. • Factors affect Diffusion
• Concentration gradient
• Electric potential across the membrane,solute
moves toward the opposite charge.
• Permeability coefficient
• Hydrostatic pressure gradient
• Temp. Higher temperature increase partial
motion and enhance diffusion.

15. • Facilitated Diffusion
• Some solute are transported across membrane by
specific channels or transporter protein located in
the membrane.
• This specific transporter is saturable and is driven
by transmembrane electrochemical
gradients.They are also show substrate specificity.
• Rate depends upon on concentration gradient of
the solute,availability of the transporter,binding
affinity of solute to transporter and rate of
conformation changes in transporter.

16. Ping Pong mechanism of faciltated
diffusion

17. • Co-transporters
• They use the gradient created by the active
transport of one substance to derive the
movement of the other solute.The gradient
used may be produced by an ATPase
pump(primary-co-transport) by other
system(secondary co-transport).

18. ION-CHANNEL
• They are transmembrane protein
• Make pore size of 5-8 nm
• Conduct rapidly
• Composed of many subunits
• Highly specific for the ions they transport.
• They open transiently to allow ion movement.
• Their activity are regulated and these are
conserved in species.

19. MEDIATORS OF ION CHANNELS
• Opening and closing of ion channels is mediated
in several ways depending upon the type of
channels mentioned below.
• By ligand bending in ligand gated channel
• By change in voltage in voltage gated channel
• By mechanical change,pressure in mechanically
gated channel.
• Permeabiltyof ion channel depends upon the
following
• Size and charge of the ion,
• Degree of hydration of ion

20. • Na+ channel
• Composed of many subunits
• α- subunit is essential,which is a large
protein(1840 a.a.),organised into four domains
clustered togather to make a central pore.
• Each domain has six transmembrane α –helical
region
• Actual channel is formed by the association of
four domains and has a pore of 5-8 nm dimeter
in it.

22. • Helices v and Vl of each domain are critical in
imparting Na+ specficity and pore formation
• Helix lV impart voltage sensitivity to the
channel
• Neuronal and muscle Na+ channels are voltage
gated channels
• Highly selective for Na+ ions.

23. • K+ channel
• Consist of our subunits of transmembrane
integral protein.
• Each subunit is a dimer.
• The four subunits are arranged to make a
inverted cone like structure.
• Ion selectivity is conferred by the lining of
channel by the carbonyl oxygen atoms of
threonine,tyrosine,glycine and valine residues.
• K+ ion get dehydrated as they enter into the
channel to fit into the channel and pass through
it.

24. • Na+ ion is too small to intract with carbonyl
oxygen in correct alignment and is rejected.
• K+ channel is also voltage gated channel.
• AQUAPORIN THE WATER CHANNEL
• They are a family of integral membrane
proteins which make water channels
• Ten types of aquaporins are known,each with a
specialized role.
• Rate of follow of water molecules through the
different aquaporins is variable.

25. • They permit movement of water molecule but
not hydronium ions.
• Therefore maintaining the pH gradient across
the membrane.
• They are small, hydrophobic, intinsic
membrane protein.
• It is highest for AqP1(109 water
molecules/sec,Aqp2 mutation cause Diabetes
insipdus.)

26. ACTIVE TRANSPORT
• It require energy(By ATP hydrolysis) to
transport a molecule uphill against the
concentration gradient.
• Primary active transport-By ATP hydrolysis
and ATP hydrolysis is directly coupled to
transport of a solute.e.g. Na-K+ ATPase pump.
• Secondary active transport-Occurs when uphill
transport of one solute is coupled to downhill
transport of other solute which has been earlier
transported by primary active transport

29. PRIMARY ACTIVE TRANSPORT SYSTEM
• ATP dependent transporters
Type Cellular location and
example
ABC-transporter ABC-ATP Binding cassette
MDR-1,ABC-1 inplasma
membrane
V-Type V=Vacuole
H+-ATPase;pumps H+ ions into
lysosomes
F-Type F=Coupling Factor
Mitochondrial ATP synthase
P-type
P=Phosphorylation
Na+-K+ATPase in plasma membrane
Ca++-ATPase in sarcoplasmic reticulm

30. SECONDARY ACTIVE
TRANSPORT
• Glucose in the intestinal wall cell is
transported by secondary active transport
along with sodium by sodium glucose
transporter-1(SGT-1).
• SGT-1 is coupled to Na+-K+ ATPase pump
which maintain the Na+ gradient across the
cell membrane.

32. TRANSPORT OF MACRO
MOLECULES
• EDOCYTOSIS-It is a process intake of fluid
and substance into cell from sroundind.
• Occurs by invagination of a part of membrane
enclosing a small amount of fluid along with
its content.
• The invagination form a vesicle which then
pinches off.
• Subsequent fusion of plasma membrane
restores the cellular membrane continuity.

34. • The vesicle transport its content to other cell
organelles by fusion with lysosome to make
secondary lysosom.
• The enzymes degrade the molecular content
into the consituent molecule.
• It require ATP,Ca++ and contractile element.
• Type of endocytosis
1 Phagocytosis
2 Pinocytosis (Two types)
1 Fluid phase pinocytosis
2 Absorptive endocytosis

36. PHAGOCYTOSIS
• Endocytosis undertaken by phagocytes like
macrophages is called phagocytosis.
• Phagocytosis involves the ingestion of large
particulate material like bacteria, viruses, dead
cell, debries etc.
• It play an important role in combating
infectious and removal of other harmful
subststances.

38. Fluid phase pinocytosis
• It is general mechanism of ingestion, like
endocytosis, undertaken by all cells in a non-
specific manner.
• It is much slower than phagocytosis.
• It does not lead to much change in the volume
or surface area of the cell.
• Ingested membrane is replaced by exocytosis
or recycling.

39. ABSORPTIVE ENDOCYTOSIS
• It is a selective, receptor mediated endocytosis
used to ingest specific substance from
extracellular space without much fluid and
other molecules.
• The substance to be ingested binds to the
receptor and is endocytosed.
• The invaginated vesicle is coated on the
cytoplasmic side with filamentous protein
clathrin.

40. • Clathrin protein is involved in the endocytosis
og ligand-receptor complex internalization as
in case of hormones. Growth factors and other
protein like transferrin.
• All these are internalized as complex with their
respective receptors.
• LDL receptors mediated internalization of
LDL occurs through clathrin coated pits.

41. EXOCYTOSIS
• Cell release molecules by exocytosis.
• It is often initiated by a signal such as
hormone, which on binding to the receptor
cause a local increase in Ca++ concentration.
• This triggers exocytosis.

43. FUNCTION OF EXO.AND
ENDOCYTOSIS
• It regulate the membrane components, various
transporter and cell function.
• Nutrition intake and secretion of products.
• Cell communication.
• Removal of microbes and antigen.
• Role in research and therapeutics.
• Endocytosis cause some
diseases(HIV,polio,hepatitis,iron toxicity)

44. IONOPHORES
• Produced by bacteria which facilitate the
transport of ions across the membrane.
• Non-protein compound
• Some are antibiotic in nature.
• Mobile ionophores bind to ion and diffuse
across the membrane.
• Channel ionophores form channel in the
membrane to transport ions.

45. IONOPHORE ION Transport Action
Valinomycin K+ Uniport;electron
egative
Nigrecin K+/H+ Antiport;electron
utral
A 2387 Ca++/2H+ do
Gramicidin H+/K+/Na+ Channel forming
Alamethicin K+ Channel forming

46. THANK YOU