Cell Membrane Composition and Function_240417_114329.pdf

Cell Membrane Composition hhvgvhghvgfghfvhgvgvghvgvggvgfgvgfgghvhgvhbhgvfgvghvfgvghvfggvgvvgggfvgvghghvgbgyygyuhujnnuyvft h g h gy hbgyvybgyv bg h h bhb

1. Cell Membrane
Alissa Laurel N. Calderon, MD, FPAFP, MMHA

2. Cell
•Fundamental unit of life
•Cells make up all living matter
•All cells arise from other cells
•The chemical reactions of an organism ,
both anabolism and catabolism, takes
place in the cell

3. Types of Cell

4. Organelles

5. Nucleus
•Contains more than 95% of the cell’s DNA
•Control center of the cell
•Where DNA replication and RNA
transcription of DNA occur

6. Parts of a Nucleus
•Nuclear envelope –double membrane structure
that separates the nucleus from the cytoplasm
•Nuclear pore complexes –these are embedded
in the nuclear envelope; control the movement
of proteins and RNAs across the nuclear
envelope
•Nucleoplasm–contains various enzymes such
as DNA polymerases and RNA polymerases for
mRNA and tRNAsynthesis

7. Parts of a Nucleus
•Chromatin–made up of coiled DNA;
stained darkly with certain dyes
•Nucleolus–second dense mass closely
associated with the inner nuclear envelope
–Nonmembranous;contains RNA polymerase,
ATPase, but no DNA polymerase
–Site of synthesis of ribosomal RNA (rRNA)
–Major site where ribosome subunits are
assembled

8. Mitochondria
•Powerhouse of the
cell
•Bounded by two
concentric
membranes that have
different properties
and biological
functions

9. Mitochondrial Membrane
•Outer mitochondrial membrane –consists
mostly of phospholipids and cholesterol;
also contains protein porin
–Porin–proteins that form channels that
permits substances with MW <10,000 to
diffuse freely across the mitochondrial
membrane

10. Mitochondrial Membrane
•Inner mitochondrial membrane
–Very rich in proteins
–Contains high proportion of the phospholipids
cardiolipin
–Impermeable to polar and ionic substances
(as opposed to outer membrane)
–Cristae –inner mitochondrial membrane is
highly folded; tightly packed inward folds are
called cristae

11. •Mitochondrial matrix –region enclosed by
the inner membrane
–Where enzymes responsible for citric acid
cycle and fatty acid oxidation are located

13. Endoplasmic Reticulum
•Extends from the cell membrane, coats
the nucleus, surrounds the mitochondria
and appears to connect directly to the
Golgi apparatus

14. Kinds of ER
•Rough ER –coated with ribosomes; near
the nucleus, it merges with outer
membrane of the nuclear envelope;
synthesizes membrane lipids and
secretory proteins
•Smooth ER –do not have attached
ribosomes; responsible with lipid
synthesis, and modifies and transports
proteins synthesized by RER

15. Golgi Apparatus
•Unique stack of smooth surfaced compartments
or cisterna
•It is usually closely associated with ER
•Has proximal or ciscompartment, a medial
compartment and a distal or trans compartment
•Serves as a unique sorting device that receives
newly synthesized proteins, all containing signal
or transit peptides from the ER
–Those proteins with no signal or transit peptides
regions are rejected by the golgiapparatus without
processing further
–Remains as cytoplasmic protein

16. Functions
•Proximal or cisside –receives the newly
synthesized proteins by the ER via transfer
vesicles
•Median part –where posttranslational
modification take place
–Where the carbohydrates and lipid precursors
are added to proteins to form glycoprotein and
lipoproteins respectively
•Distal or trans side –release proteins via
modified membranes called secretory vesicles

17. Lysosomes
•Contains packet of enzymes
•Found in all cells, except RBC
•pH inside is lower than that of the
cytoplasm
–Lysosomalenzymes have an optimal pH of 5
–Acid phosphatase is used as a marker
enzyme
–Enzymes are hydrolytic in nature

19. Peroxisomes
•Small organelles, approximately 0.5μ in
diameter
•They have no energy-coupled electron
transport systems
–Formed by budding from SER

20. Functions
•They carryout oxidation reactions in which
toxic hydrogen peroxide (H2O2) is produced,
which is destroyed by the enzyme catalase.
•Liver peroxisomes have an unusually active β-
oxidative system capable of oxidizing long
chain fatty acids (C 16 to 18 or > C 18)
–β-oxidation enzymes of peroxisomes are rather
unique in that the first step of the oxidation is
catalyzed by a flavoprotein, an “acyl Co-A oxidase”
–H2O2 produced is destroyed by catalase.

21. Biological Membrane system
•Highly dynamic two layers thick sheath like
structures formed by lipids, proteins and
carbohydrates
•Serves as closed boundaries between
different compartments of the cells
•Nuclear membrane: nucleoplasm from
cytoplasm
•Act as barriers to the passage of polar
molecules and ions

22. Cell Membrane
•Exists in viscous—gel-fluid like—and plastic
structures (ex. RBCs).
•Dynamic—exhibits rapid turnover and lateral
diffusion
•Has a thermodynamically stable and
metabolically active arrangement
•Composed of lipids, proteins and carbohydrates

23. Functions of Cell Membrane
•Selective barrier –aided by carriers and
channels, allowing exchange between the
cell and the environment
•Permits cell individuality –separates cell
from other cells
•Cell-to-cell interaction –due to hormone-
receptor interactions
•Cell adhesion to basement membrane and
other cells

24. Functions of Cell Membrane
•Transmembranesignaling –signal
transduction mechanism
•Compartmentalization
•Localize enzymes
•Excitation-response coupling
•Site for energy transduction

25. Cell Membrane
•Asymmetric, sheet-like structure with an inner
leaflet (exposed to the ICF) and an outer one
(exposed to the ECF)
–Structure is due to noncovalentassemblies that form
spontaneously in water due to the amphipathic nature
of lipids
•Two sides of the membrane are not structurally
and functionally identical
–The difference in composition of lipids and proteins
–Difference in positioning and orientation of the
membrane proteins
–Difference in the enzymatic activities of the inner and
outer surfaces

26. Cell Membrane Asymmetry
•“Inside-Outside” Asymmetry
–Due to irregular distribution of proteins
–Carbohydrates are only found externally
–Specific locations of enzymes
•Ex. In the mitochondria, enzymes involved in ETC are found on the
inner mitochondrial membrane)
–Nature of phospholipids
•outer leaflet: phosphaditylcholine, sphingomyelin, glycolipids
•Inner leaflet: phosphatidyiethanolamine, phosphatidylserine,
phosphatidylinositol
•“Regional Asymmetry”
–Villous borders, gap junctions, tight junctions
–Found in specific sites

28. Significance
•Changes in phospholipid asymmetry is
involved in various cell functions: cell
polarity, membrane trafficking and
organelle functions
•Phospholipid asymmetry is generated,
maintained and regulated by lipid
translocation or “flip-flop”

29. Composition of Cell
Membrane

30. •Composed of lipids, proteins and
carbohydrates
–40% -lipids
–60% -proteins
–1-10% -carbohydrates
•All membrane carbohydrate is covalently
attached to proteins or lipids

32. A. Lipids
•Provide basic structure; backbone
•Amphipathic due to hydrophobic (non
polar) tail and hydrophilic (polar) head –
attributing to formation of a bilayer
•With FA tails
–Saturated FAs –straight tails àorganized,
compact, crystalline membrane
–Unsaturated FAs –kinked tails àdue to
double bond, disorganized, fluid membrane

33. Lipid Bilayer
•Hydrophilic and hydrophobic interactions are
responsible for the bilayer organization of
membranes in the cells

34. Classification of Membrane Lipids
Membrane
Lipids
Phospholipids
glycolipid
sterols
Glycero-phospholipids
Sphingo-phopholipids
Galactolipids
Sphingo-glycolipids

35. 1. Phospholipids
•Glycerol-3-phosphate (phosphoglycerides)
–backbone of all phospholipids
•Polar “head” group is joined to the
hydroxyl (OH-) group of the C3 of a
glycerol by phosphodiesterlinkage
•The other OH-groups (C1 and C2) of the
glycerol is sterifiedby fatty acids

36. Glycerol-3-phosphate

37. Phospholipids
lipids with phosphate
groups. Lends to
selective permeability of
cell membrane as it
allows lipophilic
substances (O2, CO2,
alcohol) to pass through

38. Sub-Categories of
Phospholipid
•Phosphoglycerides(Glycero-phospholipids)
–most common phospholipid
–consist of a glycerol backbone + 2 fatty acid
chains connected via ester linkages +
phosphorylated alcohol
–(e.g.ethanolamine, choline, serine, glycerol,
or inositol)
–Fatty acids are even-numbered (16-18 C
atoms) which could be saturated or
unsaturated
–Simplest form is phosphatidicacid

39. Fatty acidglycerolAlcohol

40. Name of X -OHFormula of -XPhospholipid Name
Water-H Phosphatidicacid
Ethanolamine-CH2CH2NH3Phosphatidylethanolamine
Choline-CH2Ch2N(CH3)3+Phosphatidylcholine
(Lecitin)
Serine-CH2CH(NH3+)COO-Phosphatidylserine
Glycerol-CH2CH(OH)CH2OHPhosphatidylglycerol
PhosphatidylglycerollDiphosphatidylglycerol
(Cardiolipin)
MyoinositolPhosphatidylinositol

41. Cardiolipin
•Complex glycero-phospholipid
•polar head (-X) is a phosphatidylglycerol
thus structurally, a diphosphatidylglycerol
•An important component of the inner
mitochondrial membrane –constitutes
about 20%
•Lipid marker of the inner mitochondrial
membrane (not found in outer
mitochondrial membrane)

42. Cardiolipin

43. Plasmalogen
•C1 of glycerol moiety is linked to fatty acid
via an α,β-unsaturated ether linkage rather
than an ester linkage
•Present in abundance in neurons and cells
of cardiovascular system

44. Plasmalogen

45. Sphingo-phospholipids
(Sphingolipids)
•Second sub categoryof
phospholipids
•A C18 amino alcohol called
sphingosinebackbone
instead of glycerol
backbone
•The N-acyl fatty acid
derivative of sphingosineat
C2 is called Ceramide

46. Ceramide

47. •Sphingomyelin
–Most common sphingo-phospholipids
–contains a sphingosinebackbone instead of
glycerol
–A fatty acid is attached by an amide link to the
amino group of sphingosine= CERAMIDE
–Hydroxyl group of sphingosineis esterified to
phosphorylcholine
–Sphingomyelinis prominent in myelin sheath

48. Legend:
Phosphorylcholine
Sphingosine
Fatty Acid

49. 2. Glycolipids
•Polar head group holds one or more
carbohydrate moieties and its derivatives.
•Lipids conjugated with carbohydrates have
other 2 important functions, besides in the
membrane:
•Provide energy
•Acts as markers for cellular recognition

50. Classification of Glycolipids
•2 sub-categories
a.Glyceroglycolipids–glycerol backbone with
carbohydrates
-Galactolipids
-sulfolipids
b.Sphingoglycolipids–sphingosinebackbone
with carbohydrate
-Cerebrosides
-Gangliosides
-Globosides

51. Glyceroglycolipids
•have glycerol backbone with carbohydrate
heads
•2 important glyceroglycolipids:
–Galactolipids
–Glyceroglycolipids

52. Galactolipids
•The C3 of the glycerol moiety is connected
to one or more galactoseresidues by
glycosidicresidues
•The C1 and C2 of glycerol are esterified
with fatty acids
•Predominantly present in plant cells
particularly the thylakoid membranes of
chloroplasts

53. Sulfolipids
•Membrane glycolipids with sulfur
containing functional groups
•Sulfonatedglucose is joined to the C3 of
diacylglycerolin glycosidiclinkage

54. Sphingoglycolipids
•sugar attached to ceramidebackbone
rather than glycerol moieties
•found in nerve tissue
a.Cerebrosides
b.Gangliosides
c.Globosides

55. Cerebrosides
•A ceramidewith single sugar residue at
the C1-hydroxyl group
•Sugar residue is either glucose or
galactose
•Lack the phosphate group thus they are
non-ionic (no charge)
•Abundant in cell membranes of nerves
and muscles of animals
–Nerve cells –rich in galactocerebrosides

56. Cerebrosides

57. Gangliosides
•Membrane lipid with most complex
structure
•It is a glyco-sphingolipidwith many
carbohydrate moieties and one or more
sialicacids linked on the sugar chain
•About 6% of brain lipids are gangliosides
and they are first isolated from the
ganglion of brain cells
–Also abundant in the lipid rafts of plasma
membrane

58. Gangliosides

59. Globosides
•With one or more than one sugar as the
side chain of a ceramide
•Differ from gangliosidessince they lack
the sialicacid residues
•The carbohydrate moieties are usually a
combination of N-acetyl-galactosamine,D-
glucose or D-galactose

60. Globosides

61. 3. Sterols
•Third major category of membrane lipids, usually present
in eukaryotocmembranes
•Structurally consist of four fused carbon rings (A, B, C,
D) and a hydrooarbonchain (alkyl side chain)
•Rings A, B, C are 6-carbon rings; D is 5-C structure
•This fused ring structure is called the steroid nucleus
•Cyclopentanoperhydrophenanthrene
•One of its peculiarities of carbon in fused ring
structure –does not allow C-C free rotation even
though they are in single bonds

62. Steroid Nucleus

63. Cholesterol
•Most common sterol and intercalates with membrane
phospholipids
•27-C atom with 4-rings conferring rigidity
•Amphipathic with single polar hydroxyl (-OH) ‘head’ and
non-polar hydrocarbon ‘tail’
•The –OH group and hydrocarbon chain are attached to
the C3 and C17 of steroid nucleus
•Can esterify long chain fatty acids to to form cholesterol
esters such as cholesterylstearate

65. •“moderator molecule” moderates
membrane fluidity
Tm –transition temperature; temperature at
which cell membrane become
disorganized;structureundergoes from
ordered to disordered state

66. B. Proteins
•Amphipathic structures
•Determines membrane function
•Act as pumps, channels, carriers,
receptors, enzymes, structural
components, antigens

67. MEMBRANE PROTEIN
Membrane proteins have various functions:
1. Transporters
2. Enzymes
3. Cell surface receptors
4. Cell surfaceidentitymarkers
5. Cell-to-cell adhesion proteins
6. Attachments to the cytoskeleton

68. Types of Membrane Proteins
1. Integral/Transmembrane
–attached directly to phospholipids
–require detergents to be removed
–amphipathic, globular and spans the bilayer
(transmembrane) several times in certain
proteins
–asymmetrically distributed in cell membrane
–nonpolar regions of the protein are embedded
in the interior of the bilayer
–polar regions of the protein protrude from both
sides of the bilayer

69. 2. Peripheral
-do not interact directly with phospholipids
-attached to integral proteins
-usually found inside the cell
-Are free to move throughout one layer of
the bilayer
-Possess nonpolar regions that are
inserted in the lipid bilayer

71. C. Carbohydrates
•occur in association with lipids or proteins :
glycolipids or glycoproteins
•mostly found on the external membrane
surface
•functions :
o receptors
o antigens
o confers negative charge to cell
(glycocalyx)

73. Fluid-Mosaic Model
(Singer & Nicholson)
•universally accepted description of
membrane structure
•“icebergs” (proteins) floating in a “sea” of
phospholipids
•membranes undergo phasic changes from
stiff (gel or crystalline) to fluid state
•both lipids and proteins undergo "rapid
redistribution" in the plane of the
membrane ("lateral diffusion")

76. Factors Affecting Membrane
Fluidity
1. Lipid composition
-longer and more saturated fatty acid
chains exhibit higher transition temperature
-unsaturated cisbonds tend to increase
membrane fluidity
-presence of cholesterol the moderator
molecule

77. 2. Temperature
•At low temperature –fluidity is less
•As temperature increases –increase fluidity
•The hydrophobic side chains undergo a
transition from ordered state to a disordered
state
•Transition Temperature (Tm) -temperature
at which structure undergoes transition from
ordered to disordered state

78. 3. Role of Cholesterol
•Cholesterol acts as bidirectional regulator of
membrane fluidity
–At high temperature –it stabilizes the
membrane and raises its melting point
–At low temperature –it intercalates between the
phospholipids and prevents them from
clustering together and stiffens
•Without cholesterol
–Cell membrane would be too fluid, not firm
enough and too permeable to some molecules

80. Importance of Increased
Membrane Fluidity
1.Permeability to water and other
hydrophilic molecule increases
2.Lateral mobility of integral proteins
increases*
•* especially important with proteins
involved in transport and receptor proteins
3. Increased protein diffusion –since some
proteins are internalized, allows for faster
appearance

81. Artificial Membranes and
Other Special Membrane
Structures

82. A. Micelle
•are relatively small
aggregates of
amphipathic
molecules forming a
monolayer with :
o hydrophobic regions
-shielded from H20
o hydrophilic regions -
immersed or interact
with H20

83. •single-layer unlike cell membrane
•arrangement of different regions depends on the
chemical environment where the micelle is
situated
•used in detergents
•clinical application of micelles :
–are formed when bile acids (which are
amphipathic) associate with products of lipid
digestion
–bile acids-formed micelles assist in the
digestion and absorption of fat plus ADEK

84. B. Liposomes
•Vesicles surrounded with lipid bilayer
•Consist of phospholipids that are of
natural or synthetic origin
•Lipid content can be varied allowing for
examination of varying lipid composition
on certain functions (ie., transport)
•In the study of factors that affect protein
and enzyme function
•May be used for specific drug delivery and
gene therapy

86. C. Tight Junctions
•Located below the apical surface of
epithelial cells
•Prevents the diffusion of macromolecules
between them
•Composed of proteins occludin, claudins
•Sites of paracellulartransport
•Means of attachment

87. Tight Junctions

88. •Prevents diffusion of macromolecules
•Allows paracellulartransport of water (e.g.
Na+ K+ ATPase)
•Physical connection between cells

89. D. Gap Junctions
•Low resistance connection between cells
•More functional connection
•Made of connexons(made of connexins)
and are aligned with another cell
•Transports small ions, molecules, and
impulses
•In heart muscles, they are known as
syncytium

90. Gap Junctions

91. Desmosomes
•Junctions which act like spot welds between adjacent
epithelial cells
•Involves a complex of proteins, some extend across the
membrane while others anchor the junction within the
cell
•Pin adjacent cells together, ensuring that cells in organs
and tissues that stretch, such as skin and cardiac
muscle, remianconnected in an unbroken sheet.
•Cathedrins, specialized adhesion proteins, attach to a
structure called the cytoplasmic plaque which connects
to the intermediate filaments and helps anchor the
junction

92. Desmosome

94. E. Lipid Raft
•are dynamic areas of the exoplasmic
leaflet of the lipid bilayer enriched in
cholesterol, sphingolipidsand proteins
•involved in and enhances signal
transduction by clustering elements of the
signaling systems

97. Caveolae
•Derived from lipid rafts
•Usually contain special protein called
caveolin-1, which is involved in the
formation of lipid rafts
•Also takes part in signal transduction

98. Special Characteristics of Red
Cell Membrane

99. Integral Protein
•Two major integral proteins in RBC:
–Glycophorin
–Band-3-protein

100. Glycophorin
•Glycoproteins; contains 60% carbohydrates by weight
•Oligosaccharides are linked to serine, threonine and
asparagine residues
•RBC membrane contains about 6 ×105 glycophorin
molecules.
•The polypeptide chain of glycophorincontains 130 amino
acid residues.
–A sequence of 23 hydrophobic amino acid residues lies within the
non-polar hydrocarbon phase of the phospholipid bilayer, tightly
associated with phospholipids and cholesterol.
–This 23 amino acid residue sequence has an α-helical
conformation.

102. Functions
•Some of the oligosaccharides of
glycophorinare the M and N blood group
antigens.
•Other carbohydrates bound to glycophorin
are sites through which the influenza virus
becomes attached to red blood cells.

103. Band-3-Protein
•Integral protein found in red cell membrane.
•It is dimerichaving molecular weight of
93,000.
•The polypeptide chain of the dimer is thought
to traverse the membrane about a dozen time.
–Both the C and N terminals of band-3-protein are
on the cytosolic side of the membrane.
–The N-terminal residues extend into the cytosol
and interact with components of the cytoskeleton.
•

104. Functions
•plays an important role in the function of red
blood cells.
–As red blood cells flow through the capillaries of
the lungs, they exchange bicarbonate anions
(HCO3–.) produced, by the reaction of CO2 and
H2O, for chloride (Cl–) ions.
–This exchange occurs by way of a channel in
band-3-protein, which forms a Pore through the
membrane. .

105. Peripheral Protein
•The inner face of the red blood cells
membrane is laced with a network of proteins
called cytoskeletons that stabilizes the
membrane and is responsible for the
biconcave shape of the cells:
•The special peripheral membrane proteins
participate in this stability of red cells are:
–Spectrin
–Actin
–Ankyrinand Band 4, 1 protein.

106. Spectrin
•Spectrinconsists of an α-chain, having
molecular weight 240,000 and a β-chain having
molecular weight 220,000.
•It is a fibrous protein in which the polypeptide
chains are thought to coil around each other to
give an α-β dimer, 100 nm long and 5 nm in
breadth.
•Spectrindimers are linked through short chains
of actin molecules and band 4, 1 proteins to
form α2 β2 tetramers.

107. Actin
•In red blood cells and other nonmuscle
cells, actin is a component of the
cytoskeleton.
•An erythrocyte contains 5 ×105 actin
molecules.
–About 20 actin molecules polymeriseto form
short actin filaments.

108. Ankyrin
•Where the network of spectrin, actin and band 4, 1 protein
are attached
–These network of protein forms the skeleton of the red
blood cell, but none of these proteins is attached directly to
the membrane.
•It has a molecular weight 200,000.
•The protein has 2 domains: One binds to spectrin, and the
other to the N-terminal region of band-3-protein that extends
into the cytoskeleton.
•It is now known that the protein network can also be bound
directly to glycophorin(integral protein) or to band-3-protein.

109. Clinical Aspect
•Hereditary spherocytosis and hereditary elliptocytosisare
inherited genetic abnormalities of red cells in which red cells
are of abnormal shape.
–In hereditary spherocytosis the red cells are spherical and in hereditary
elliptocytosisthey are ellipsoidal.
–These defects in shape of red blood cells lead to increased haemolysis,
anaemiaand jaundice.
–These abnormally shaped red blood cells are fragile and have shorter life
than normal erythrocytes.
•Defect: They result from mutations in the genes coding for
proteins of the membrane.
–The abnormality may be from defective spectrinthat is unable to bind
either ankyrinor band 4, 1 protein and in some cases band 4, 1 protein
is absent.