Lipid200 structure and function

LIPID STRUCTURE, FUNCTION
AND METABOLISM
Oheneba C. K. Hagan

Objectives
• Know the types of lipids
• Know the structure, function, classification
and clinical importance of lipids

Lipids
 The lipids are a heterogeneous group of naturally occuring
compounds; including fats, oils, steroids, waxes, and related
compounds, that are related more by their physical than by their
chemical properties.
 They have the common property of being
(1) relatively insoluble in water and
(2) soluble in nonpolar solvents such as ether and chloroform.

Function
 Storage form of energy
 Important dietary components because of their
high energy value and also because of the fat-
soluble vitamins and the essential fatty acids
contained in the fat of natural foods.
 Structural components of biomembranes
 Serve as thermal insulators in the subcutaneous
tissues and around certain organs
 Nonpolar lipids act as electrical insulators,
allowing rapid propagation of depolarization
waves along myelinated nerves

 Provide shape and contour to the body
 Act as metabolic regulators
 Combinations of lipid and protein
(lipoproteins) are important cellular
constituents, occurring both in the cell
membrane and in the mitochondria, and
serving also as the means of transporting
lipids in the blood.

Classification of lipids
Simple lipids: Esters of fatty acids with various
alcohols.
• a. Fats: Esters of fatty acids with glycerol. Oils
are fats in the liquid state.
• b. Waxes: Esters of fatty acids with higher
molecular weight monohydric alcohols

Classification
2. Complex lipids: Esters of fatty acids containing groups in addition
to an alcohol and a fatty acid.
• a. Phospholipids: Lipids containing, in addition to fatty acids and an
alcohol, a phosphoric acid residue. They frequently have nitrogen-
containing bases and other substituents, eg, in
glycerophospholipids the alcohol is glycerol and in
sphingophospholipids the alcohol is sphingosine.
• b. Glycolipids (glycosphingolipids): Lipids containing a fatty acid,
sphingosine, and carbohydrate.
• c. Other complex lipids: Lipids such as sulfolipids and aminolipids.
Lipoproteins may also be placed in this category.
3. Derived Lipids: Sterols, Eicosanoids, Vit ADEK,

Dietary fat Composition
More than 95% are triglycerides, the
other are
Cholesterol,
Cholesteryl esters,
Phospholipids, and
Unesterified fatty acids.

Dietary sources of Lipids
 Animal Sources
Dairy products- Meat, butter, ghee
Meat and Fish, Pork, eggs
 Vegetable Sources
Cooking oils- Sun flower oil, Mustard oil,
Ground nut oil
Fats from other vegetable sources

Lipid Digestion
Acid stable lingual and gastric lipases. SCFA (<12C) eg in milk
Problem of lipids- hydrophobic and enzymes work in hydrophilic
environment
Bile acids produced in liver and stored in gall bladder
Forms amphipathic micelles in small intestine with fat globules
Pancreatic lipases enter micelles and digest lipids

• Triglycerides (TG)
TG + H2O → Diglyceride + fatty acid (FA)
Diglyceride + H2O → Monoglyceride (MG) + FA
• Cholesterol esters & phospholipids (PL)
↓ esterase ↓ phospholipases
FA + cholesterol (chol) FA + lyso PL

Micelles containing the FFA, Monoacylglycerol, cholesterol and lysophospholipids are presented
to the duodenal and jejunal enterocytes for absorption

Clinical Correlation
The drug Orlistat for weight loss inhibits pancreatic lipase leading
reduced TAG malabsorption and weight loss.
Malabsorption of lipids (steatorrhoea)
Results
From bile acid insufficiency eg liver disease, gastrointestinal resection.
Pancreatic insufficiency eg pancreatitis
 The drug ezetimibe blocks a protein that specifically mediates
cholesterol transport across the apical plasma membrane of
enterocytes.
 Ezetimibe has been shown to be effective at reducing levels of LDL
cholesterol, particularly when combined with a statin, a drug that
inhibits cholesterol synthesis in the liver.

Glycerol
• Structure  Also called ‘Glycerin’.
 Trihydric alcohol as it contains
three hydroxyl groups
 Can be obtained from diet,
from lipolysis of fats in adipose
tissue and from glycolysis.
 Can be utilized for the
synthesis of triacylglycerols,
phospholipids, glucose or can
be oxidized to provide energy
 Used as a solvent in the
preparation of drugs and
cosmetics
 Nitroglycerine is used as a
vasodilator
glycerol
H2C
HC
H2C
OH
OH
OH

Fatty Acids
Fatty acids are aliphatic carboxylic acids
Have the general formula R-(CH2)n-COOH
They occur mainly as esters in natural fats and
oils but do occur in the unesterified form as free
fatty acids, a transport form found in the
plasma.
Fatty acids that occur in natural fats are
usually straight-chain derivatives containing an
even number of carbon atoms.
The chain may be saturated (containing no
double bonds) or unsaturated (containing one or
more double bonds).
6/29/2012 17Biochemistry for medics

Classification of Fatty Acids
Fatty acids can be classified in many ways-
1) According to nature of the hydrophobic
chain-
a) Saturated
b) Unsaturated
c) Branched chain fatty acids
d) Substituted Fatty acids
Saturated fatty acids do not contain double
bonds, while unsaturated fatty acids contain
double bonds

Saturated Fatty Acids
Saturated fatty acids may be envisaged as
based on acetic acid (CH3 —COOH) as the first
member of the series in which —CH2 — is
progressively added between the terminal CH3 —
and —COOH groups.
Fatty acids in biological systems usually
contain an even number of carbon atoms,
typically between 14 and 24. The 16- and 18-
carbon fatty acids are most common.
The hydrocarbon chain is almost invariably
unbranched in animal fatty acids. A few
branched-chain fatty acids have also been
isolated from both plant and animal sources.

Saturated Fatty Acids
Number of C
atoms
Common Name Systemic Name Formula
2 Acetic acid Ethanoic acid CH3COOH
4 Butyric acid Butanoic acid CH3(CH2)2COOH
6 Caproic acid Hexanoic acid CH3(CH2)4COOH
8 Caprylic acid Octanoic acid CH3(CH2)6COOH
10 Capric acid Decanoic acid CH3(CH2)8COOH
12 Lauric acid Dodecanoic acid CH3(CH2)10COOH
14 Myristic acid Tetradecanoic acid CH3(CH2)12COOH
16 Palmitic acid Hexadecanoic acid CH3(CH2)14COOH
18 Stearic acid Octadecanoic acid CH3(CH2)16COOH
20 Arachidic acid Eicosanoic acid CH3(CH2)18COOH
22 Behenic acid Docosanoic acid CH3(CH2)20COOH

Unsaturated fatty Acids
Unsaturated fatty acids may further be divided as follows-
(1) Monounsaturated (monoethenoid, monoenoic) acids, containing
one double bond.
(2) Polyunsaturated (polyethenoid, polyenoic) acids, containing two
or more double bonds.
The configuration of the double bonds in most unsaturated fatty
acids is cis.
The double bonds in polyunsaturated fatty acids are separated by at
least one methylene group.

Nomenclature of Fatty acids
The systematic name for a fatty acid is derived from the
name of its parent hydrocarbon by the substitution of oic
for the final e.
For example, the C18 saturated fatty acid is called
octadecanoic acid because the parent hydrocarbon is
octadecane.
A C18 fatty acid with one double bond is called
octadecenoic acid; with two double bonds, octadecadienoic
acid; and with three double bonds, octadecatrienoic acid.
The notation 18:0 denotes a C18 fatty acid with no double
bonds, whereas 18:2 signifies that there are two double
bonds.

Nomenclature of Fatty acids(Contd.)
• Carbon atoms are numbered
from the carboxyl carbon
(carbon No. 1). The carbon
atoms adjacent to the carboxyl
carbon (Nos. 2, 3, and 4) are
also known as the α ,β, and g
carbons, respectively, and the
terminal methyl carbon is
known as the ω or n-carbon.
The position of a double bond
is represented by the symbol
∆followed by a superscript
number.
• eg, ∆ 9 indicates a double bond
between carbons 9 and 10 of
the fatty acid;

Nomenclature of Fatty acids(Contd.)
Alternatively, the position of a double bond can
be denoted by counting from the distal end, with
the ω-carbon atom (the methyl carbon) as
number 1.
ω9 indicates a double bond on the ninth carbon
counting from the ω-carbon.

Cis and Trans-Isomers in unsaturated
fatty acids
• Depending upon the
orientation of the radicals
around the axis of the double
bond-
• Cis- If the radicals are on the
same side of the double bond
• Trans- If the radicals are on the
opposite side
• In humans UFA are in cis form
• Trans arises from
hydrogenation of FA (High
Trans FA leads to increased
cardiovascular accidents)
6/29/2012 Biochemistry for medics 25

Biological Importance of fatty acids-
1-Fatty acids are the building blocks of
dietary fats. The human body stores such fats
in the form of triglycerides.
2)- Fatty acids are also required for the
formation of membrane lipids such as
phospholipids and glycolipids.
3) -They are required for the esterificaton of
cholesterol to form cholesteryl esters.
4) They act as fuel molecules and are
oxidized to produce energy.

Triglycerides
The triacylglycerols are esters of the trihydric alcohol,
glycerol and fatty acids.
Mono- and Diacylglycerol, wherein one or two fatty acids
are esterified with glycerol, are also found in the tissues
 Naturally occurring fats and oils are mixtures of
triglycerides.
FUNCTIONS
• Major lipid in the body and diet
• Stored fat provides about 60% of the body’s resting
energy needs – compactly!
• Insulation and protection
• Carrier of fat-soluble compounds
• Sensory qualities – flavor and texture

Properties of triglycerides
Insoluble in water
Specific gravity is less than 1.0,
consequently all fats float in water
Oils are liquids at 200C, they contain higher
proportion of Unsaturated fatty acids
Fats are solid at room temperature and
contain saturated long chain fatty acids
Triglycerides are the storage form of energy
in adipose tissue

Waxes
They are esters of higher fatty acids with higher
mono hydroxy aliphatic alcohols(e.g. Cetyl alcohol)
 Have very long straight chain of 60-100 carbon
atoms
They can take up water without getting dissolved in
it
Used as bases for the preparation of cosmetics,
ointments, polishes, lubricants and candles.
 In nature, they are found on the surface of plants
and insects.

Phospholipids
Contain in addition to fatty acids and
glycerol/or other alcohol, a phosphoric acid
residue, nitrogen containing base and other
substituents.
Phospholipids may be regarded as
derivatives of phosphatidic acid , in which the
phosphate is esterified with the —OH of a
suitable alcohol.
They are amphipathic molecules containing
a polar head and a hydrophobic portion

Phospholipids
33Biochemistry for medics6/29/2012

Classification of phospholipids
Based on nature of alcohol-
1)Glycerophospholipids- Glycerol is the alcohol group.
Examples-
o Phosphatidyl choline
o Phosphatidyl ethanolamine
o Phosphatidyl serine
o Phosphatidyl inositol
o Phosphatidic acid
o Cardiolipin
o Plasmalogen
o Platelet activating factor
o Phosphatidyl Glycerol
2)Sphingophospholipids- Sphingol is the alcohol group
Example- Sphingomyelin

1)Glycerophospholipids
1) Phosphatidylcholines (Lecithins )
Phosphoacylglycerols containing choline are
the most abundant phospholipids of the cell
membrane
 Are present a large proportion of the body's
store of choline.
Dipalmitoyl lecithin is a very effective surface-
active agent and a major constituent of the
surfactant preventing adherence, due to surface
tension, of the inner surfaces of the lungs. Its
absence from the lungs of premature infants
causes respiratory distress syndrome.

Glycerophospholipids(Contd.)
2) Phosphatidyl ethanolamine (cephalin)-
 Structurally similar to Lecithin with the exception that the base
Ethanolamine replaces choline
Brain and nervous tissue are rich in Cephalin
3) Phosphatidyl Serine-(found in most tissues) differ from
phosphatidylcholine only in that serine replaces choline
4) Phosphatidylinositol -The inositol is present in
phosphatidylinositol as the stereoisomer,
myoinositol.Phosphatidylinositol 4,5-bisphosphate is an
important constituent of cell membrane phospholipids; upon
stimulation by a suitable hormone agonist, it is cleaved into
diacylglycerol and inositol trisphosphate, both of which act as
internal signals or second messengers.

Glycerophospholipid- structures

5) Cardiolipin –
Abundantly found in mitochondrial membrane of the heart
tissues.
Barth syndrome due to lack of enzyme (tafazzin) involved
in its synthesis
6) Plasmalogens –ether linkage
constitute as much as 10% of the phospholipids of brain
and muscle.
Typically, the alkyl radical is an unsaturated alcohol .
In some instances, choline, serine, or inositol may be
substituted for ethanolamine.

7) Platelet activating factor (PAF)- ether linkage
Ether glycerophospholipid
Contains an unsaturated alkyl group in an ether link to carbon -1
An acetyl residue at carbon 2 of the glycerol backbone.
Synthesized and released by various cell types
PAF activates inflammatory cells and mediates hypersensitivity, acute
inflammatory and anaphylactic reactions
Causes platelets to aggregate and degranulate and neutrophils and alveolar
macrophages to generate superoxide radicals
8) Phosphatidyl Glycerol-
Formed by esterification of phosphatidic acid with glycerol
Diphosphatidyl glycerol, cardiolipin is found in the mitochondrial membrane

2)Sphingophospholipids
Sphingomyelin-
Backbone is sphingosine (amino
alcohol instead of glycerol)
A long chain fatty acid is
attached to amino group of
sphingosine to form Ceramide
The alcohol group at carbon-1of
sphingosine is esterified to
phosphoryl choline, producing
sphingomyelin
Sphingomyelin is an important
component of myelin of nerve
fibers

Functions of Phospholipids
Components of cell membrane, mitochondrial membrane and
lipoproteins
Participate in lipid absorption and transportation from intestine
Play important role in blood coagulation
 Required for enzyme action- especially in mitochondrial electron
transport chain
Choline acts as a lipotropic agent
Membrane phospholipids acts as source of Arachidonic acid
Act as reservoir of second messenger- Phosphatidyl Inositol
Act as cofactor for the activity of Lipoprotein lipase
Phospholipids of myelin sheath provide insulation around the nerve
fibers
Dipalmitoyl lecithin acts as a surfactant

Glycolipids(Glycosphingolipids)
 Glycolipids differ from
sphingomyelins in that they do
not contain phosphoric acid and
the polar head function is
provided by monosaccharide or
oligosaccharide attached directly
to ceramide by an O- glycosidic
linkage.
 The number and type of
carbohydrate moieties present,
determine the type of
glycosphingolipid. There are two
types of Glycolipids-
 A) Neutral glycosphingolipids
 B) Acidic glycosphingolipids

1. Cerebrosides
2. Sulfatides
3. Globosides
4. Gangliosides
Types of
Glycolipids

a) Neutral Glycosphingolipids
Cerebrosides- These are ceramide
monosaccharides, that contain either a molecule of
galactose(Galactocerebroside)or
glucose(Glucocerebroside)
Found predominantly in the brain and nervous
tissue with high concentration in myelin sheath
Ceramide oligosaccharides (Globosides) are
produced by attaching additional monosaccharides to
Glucocerebroside.
Lactosyl ceramide contains lactose (Galactose and
Glucose attached to ceramide)
Eg lactosylcerebroside

b) Acidic Glycosphingolipids (Gangliosides)
They are negatively charged at
physiological pH
The negative charge is imparted by N-
acetyl Neuraminic acid(Sialic acid)
Brain gangliosides may contain up to four
Sialic acid residues and based on that they
are-GM, GD, GT and GQ, containing 1,2,3 or 4
Sialic acid residues

Functions of Glycosphingolipids
They occur particularly in the outer leaflet of
the plasma membrane, where they contribute to
cell surface carbohydrates.
They act as cell surface receptors for various
hormones, and growth factors
Play important role in cellular interactions,
growth and development
They are source of blood group antigens and
various embryonic antigens
GM1 acts as a receptor for cholera toxin in
human intestine

3) Sulfolipids(Sulfoglycosphigolipids)
 They are cerebrosides that contain sulfated
galactosyl residues
Negatively charged at physiological pH
Found predominantly in nerve tissue and
kidney
Failure of degradation causes them to
accumulate in nervous tissues

Lipid storage diseases(Sphingolipidosis)
Disease Enzyme deficiency Nature of lipid
accumulated
Clinical Symptoms
Tay Sach’s Disease Hexosaminidase A GM2 Ganglioside Mental retardation,
blindness, muscular
weakness
Fabry's disease α-Galactosidase Globotriaosylceramide Skin rash, kidney
failure (full symptoms
only in males; X-
linked recessive).
Metachromatic
leukodystrophy
Arylsulfatase A Sulfogalactosylceramide Mental retardation
and Psychologic
disturbances in
adults;
demyelination.

Lipid storage diseases(Sphingolipidosis)-
contd.
Disease Enzyme deficiency Nature of lipid
accumulated
Clinical symptoms
Krabbe's disease β-Galactosidase Galactosylceramide Mental retardation;
myelin almost absent.
Gaucher's disease β -Glycosidase Glucosyl ceramide Enlarged liver and
spleen, erosion of long
bones, mental
retardation in infants.
Niemann-Pick disease Sphingomyelinase Sphigomyelin Enlarged liver and
spleen, mental
retardation; fatal in
early life.
Farber's disease Ceramidase Ceramide Hoarseness, dermatitis,
skeletal deformation,
mental retardation;
fatal in early life

• Fatty acids, phospholipids, sphingolipids, bile
salts, and, to a lesser extent, cholesterol contain
polar groups. Therefore, part of the molecule is
hydrophobic, or water-insoluble; and part is
hydrophilic, or water-soluble. Such molecules are
described as amphipathic
• They become oriented at oil:water interfaces
with the polar group in the water phase and the
nonpolar group in the oil phase.
• A bilayer of such amphipathic lipids is the basic
structure in biologic membranes
Amphipathic lipids

• Liposomes-Liposomes may be formed by sonicating an
amphipathic lipid in an aqueous medium.
• They consist of spheres of lipid bilayers that enclose
part of the aqueous medium.
• Liposomes are of potential clinical use—particularly
when combined with tissue-specific antibodies—as
carriers of drugs in the circulation, targeted to specific
organs, eg, in cancer therapy.
• In addition, they are used for gene transfer into
vascular cells and as carriers for topical and
transdermal delivery of drugs and cosmetics.
Amphipathic lipids

OTHER LIPIDS
Cholesterol  Cholesterol occurs both as free form or in ester form
 In cholesteryl ester, the hydroxyl group on position 3 is esterified
with a long-chain fatty acid.
 Cholesterol esters are formed by the transfer of acyl group by Acyl
transferases
 In plasma, both forms are transported in lipoproteins
 Plasma low-density lipoprotein (LDL) is the vehicle of uptake of
cholesterol and cholesteryl ester into many tissues.
 Free cholesterol is removed from tissues by plasma high-density
lipoprotein (HDL) and transported to the liver, where it is
eliminated from the body either unchanged or after conversion to
bile acids in the process known as reverse cholesterol transport
 A sum total of free and ester cholesterol in serum is called serum
total cholesterol

Significance of Cholesterol
Cholesterol is widely distributed in all cells of the
body but particularly in nervous tissue.
It is a major constituent of the plasma membrane
and of plasma lipoproteins.
It is synthesized in many tissues from acetyl-CoA
and is the precursor of all other steroids in the body,
including corticosteroids, sex hormones, bile acids,
and vitamin D.
Cholesterol is a major constituent of gallstones.
Its chief role in pathologic processes is as a factor in
the genesis of atherosclerosis of vital arteries, causing
cerebrovascular, coronary, and peripheral vascular
disease.

Eicosanoides
20 CARBON CONTAINING FATTY ACIDS GENERATED FROM
ARACHIDONIC ACID
• Discovered in prostate gland secretions
• Synthesized in all tissues
• Acts as local hormones
• Function in even low concentrations

EICOSANOIDES
Prostanoides Leukotrienes
Prostaglandins
Thromboxanes
Prostacyclins
Lipoxins
COX LOX

Prostaglandins
• Fatty acid-like substances
• Produced in prostate
– small amounts produced
in all tissue
• Synthesized from
Arachidonic Acid
COOH
CH3
Arachidonic Acid
COOH
O
HO OH
CH3
PGE2 (a prostaglandin)
steps

Prostaglandins
• PGF2
– induce labor
– therapeutic abortion
– lowers bp
– used to treat asthma
• PGE2
– causes hypertension
• PGE1
– used as a nasal decongestant
COOH
O
HO OH
CH3
PGE2 (a prostaglandin)

Thromboxanes
O
O
OH
COOH
•Induce Plaelet aggregation
•When a blood vessel is ruptured,
platelets congregate and PGH2
causes Them to clot together
Aspirin blocks the effect and acts
A blood thinner
PGH2

Prostaglandins / Leukotriene
• Leukotrienes
– Occur mainly in leukocytes (white
blood cells)
– Long lasting muscle contractions
especially in the lungs where they
cause Asthma-like attacks
CH3
OH OHOH
COOH
Leukotriene B4

Separation of lipids
• Liquid-liquid extraction
(chloroform-methanol mix)
• Liquid-solid extraction
(adsorption chromatography)
• Gas liquid chromatography
• Mass spectrometry

STRUCTURE AND FUNCTION
OHENEBA HAGAN
CELL MEMBRANES

What is a membrane?
• Membranes are the borders between
different regions of a cell.
• The plasma membrane borders the entire
cell separating the internal environment
from the external environment

Membrane Structure
• Lipids and proteins are the chief ingredients
of membrane
– Phospholipid is amphipathic, both a
hydrophobic and a hydrophilic region
– Membrane proteins are also amphipathic
• Phospholipid is arranged as a bilayer
– Hydrophilic heads exposed, hydrophobic tails
protected
• Proteins are embedded in the phospholipid
bilayer

Membrane Structure
• Not all membranes are identical
– Membranes with different functions differ in their
chemical composition and structure
• Fluid Mosaic Model best describes our current
understanding of membrane structure
– a mosaic of proteins bobbing in a fluid bilayer of
phospholipids

Figure 7.5
Glyco-
protein
Carbohydrate
Glycolipid
Microfilaments
of cytoskeleton
EXTRACELLULAR
SIDE OF
MEMBRANE
CYTOPLASMIC SIDE
OF MEMBRANE
Integral
protein
Peripheral
proteins
Cholesterol
Fibers of extra-
cellular matrix (ECM)

Fluidity
• Membranes are maintained by
hydrophobic interactions of the
phospholipids resulting in the
alignment of the polar phosphate
regions toward the aqueous
environment and the nonpolar
regions’ hydrocarbon chains
toward each other.
• Membranes are in motion with fast
drifting lipids and slower drifting
proteins

Factors affecting fluidity
• As temperatures cool, membranes switch from a
fluid state to a solid state
• The temperature at which a membrane solidifies
depends on the types of lipids
• Membranes rich in unsaturated fatty acids are
more fluid than those rich in saturated fatty acids
• Membranes must be fluid to work properly

• The steroid cholesterol has different effects on
membrane fluidity at different temperatures
• At warm temperatures (such as 37°C),
cholesterol restrains movement of
phospholipids
• At cool temperatures, it maintains fluidity by
preventing tight packing

Fluidity Influences Permeability
• Permeability deals with the movement of materials
across a membrane
• The hydrophobic portion of the lipid bilayer is
selectively permeable; allowing only certain
substances to cross

Mosaic
• Combination of proteins
makes membrane unique
• Membrane proteins may
be fluid or anchored
• Proteins may penetrate the bilayer fully (integral) or
reside on the surfaces of membranes (peripheral)
• Integral proteins typically have hydrophobic regions that
span the bilayer as a result of nonpolar amino acids
arranged as helices
• Anchored proteins strengthen membranes

The Main Classes of Membrane Proteins
Membrane proteins are classified according to their mode of attachment to the membrane. Integral
membrane proteins contain one or more hydrophobic regions that are embedded within the lipid
bilayer. Peripheral membrane proteins are too hydrophilic to penetrate into the membrane but are
attached to the membrane by electrostatic and hydrogen bonds that link them to adjacent
membrane proteins or to phospholipid head groups. Lipid-anchored proteins are hydrophilic and do
not penetrate into the membrane; they are covalently bound to lipid molecules that are embedded
in the lipid bilayer. (f) Proteins on the inner surface of the membrane are usually anchored by either a
fatty acid or a prenyl group. (g) On the outer membrane surface, the most common lipid anchor is
glycosylphosphatidylinositol (GPI).

Protein function
• Plasma membrane
proteins serve diverse
functions including:
– Transport
– Enzymatic activity
– Signal transduction
– Intercellular joining
– Cell-cell recognition
– Attachment to the
cytoskeleton and
extracellular matrix

Transport of Substances Across the
Plasma Membrane (PM)
1. Passive Transport
– (Simple) Diffusion
– Facilitated diffusion
– Osmosis
2. Active Transport
3. Bulk Flow
– Endocytosis
– Exocytosis

Factors Affecting Diffusion Rate
• Steepness of concentration gradient
– Steeper gradient, faster diffusion
• Molecular size
– Smaller molecules, faster diffusion
• Temperature
– Higher temperature, faster diffusion

Simple Diffusion
Nonpolar, hydrophobic molecules diffuse
directly through the lipid bilayer
Simple diffusion does not require the use of
transport proteins.
Examples: O2, CO2, CO, NO, steroids other
lipophilic substances, H2O (exception through
osmotic forces), ethanol
Polar, hydrophilic substances cannot pass
directly through the lipid bilayer
Examples: ions, carbohydrates

Facilitated Diffusion
 In facilitated diffusion small polar
molecules and ions diffuse through
passive transport proteins (carriers
and channels).
• Channel proteins provide corridors that
allow a specific molecule or ion to
cross the membrane
• Carrier proteins undergo a subtle
change in shape that translocates the
solute-binding site across the
membrane
 No energy needed
• Most passive transport proteins
are solute specific
• Example: glucose enter/leaves
cells through facilitated diffusion

Types of Transport Systems
Movement of single
molecule at a time
Simultaneous transport of
two different molecules in
same direction
Simultaneous transport of
two different molecules in
opposite directions

Osmosis
• Diffusion of water across a differentially
permeable membrane
• Water moves from [high]  [low]

Normal RBCs
Isotonic Solution
The Effects of Osmosis
Equal movement of water
into and out of cells
Net movement of
water out of cells Net movement of
water into cells
Shriveled RBCs
Swollen RBCs
Hypertonic Solution Hypotonic Solution

ACTIVE TRANSPORT
• Active transport is the movement of particles
across the plasma membrane against the
concentration gradient, that is from a region of low
concentration to a region of high concentration.
• Energy is provided by adenosine triphosphate (ATP)
molecules.
• Active transport also require a specific carrier
protein to carries molecules in or out of the cell.
• Examples of active transport in biology:
Absorption of glucose and amino acids by cell in
the small intestine.
Na+K+ ATPase, CFTR (chloride channels-Cystic fibrosis

Cytoplasmic Na+ bonds to
the sodium-potassium pump
CYTOPLASM
Na+
[Na+] low
[K+] high
Na+
Na+
EXTRACELLULAR
FLUID
[Na+] high
[K+] low
Na+
Na+
Na+
ATP
ADP
P
Na+ binding stimulates
phosphorylation by ATP.
Na+
Na+
Na+
Phosphorylation causes
the protein to change its
conformation, expelling Na+
to the outside.
P
Extracellular K+ binds
to the protein, triggering
release of the phosphate
group.
P
P
Loss of the phosphate
restores the protein’s
original conformation.
K+ is released and Na+
sites are receptive again;
the cycle repeats.

Bulk Flow
• Vesicles are used to transport large
particles across the PM.
– Requires energy
• Types:
– Exocytosis
– Endocytosis
• Phagocytosis, pinocytosis, receptor-mediated

Bulk Flow
• Exocytosis
–Cytoplasmic vesicle merges with the PM
and releases its contents
–Example:
• Golgi body vesicles merge with the PM an
release their contents
• How nerve cells release neurotransmittors

Vesicle
Fluid outside cell
Protein
Cytoplasm
Exocytosis

Endocytosis
Endocytosis
PM sinks inward, pinches off and forms a vesicle
Vesicle often merges with Golgi for processing and
sorting of its contents

Endocytosis - terms
• Phagocytosis – cell eating
– Membrane sinks in and captures solid
particles for transport into the cell
– Examples:
• Solid particles often include: bacteria, cell
debris, or food
• Pinocytosis – cell drinking
– Cell brings in a liquid

Receptor Mediated Endocytosis
1. Receptor proteins on PM bind specific
substances (vitamins, hormones..)
2. Membrane sinks in and forms a pit
– Called a coated pit
3. Pit pinches closed to form a vesicle around
bound substances
• Cytoskeleton aids in pulling in the membrane and
vesicle formation

Fig. 5-9c
Coated
vesicle
Coated
pit
Specific
molecule
Receptor-mediated endocytosis
Coat protein
Receptor
Coated
pit
Material bound
to receptor proteins
Plasma membrane

Lipid200 structure and function

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