Mary K.

Campbell
Shawn O. Farrell
http://academic.cengage.com/chemistry/campbell

Chapter Eight
Lipids and Proteins Are Associated in
Biological Membranes

Paul D. Adams • University of Arkansas

What is a Lipid
• Lipids: a heterogeneous class of naturally occurring organic
compounds classified together on the basis of common
solubility properties
• insoluble in water, but soluble in aprotic organic solvents
including diethyl ether, chloroform, methylene chloride, and
acetone
• Amphipathic in nature
• Lipids include:
• Open Chain forms
• fatty acids, triacylglycerols, sphingolipids,
phosphoacylglycerols, glycolipids,
• lipid-soluble vitamins
• prostaglandins, leukotrienes, and thromboxanes
• Cyclic forms
• cholesterol, steroid hormones, and bile acids
Fatty Acids
• Fatty acid: an unbranched-chain carboxylic acid, most commonly of 12 -
20 carbons, derived from hydrolysis of animal fats, vegetable oils, or
phosphodiacylglycerols of biological membranes
• In the shorthand notation for fatty acids
• the number of carbons and the number of double bonds in the
chain are shown by two numbers, separated by a colon
Fatty Acids (Cont’d)
Length of fatty acid plays a role in its chemical character
• Usually contain even numbers of carbons (can contain odd,
depending on how they are biosynthesized)
• FA that contain C=C, are unsaturated: If contain only C-C
bonds, they are saturated
Fatty Acids (Cont’d)
• In most unsaturated fatty acids, the cis isomer predominates;
the trans isomer is rare

• Unsaturated fatty acids have lower melting points than their

saturated counterparts; the greater the degree of
unsaturation, the lower the melting point
Triacylglycerols
• Triacylglycerol (triglyceride): an ester of glycerol with three
fatty acids

• natural soaps are prepared by boiling triglycerides

(animal fats or vegetable oils) with NaOH, in a
reaction called saponification (Latin, sapo, soap)
Soaps
• Soaps form water-insoluble
salts when used in water
containing Ca(II), Mg(II),
and Fe(III) ions (hard
water)

• Reactions with acids/bases

as catalysts

• Salts formed by
saponification
Phosphoacylglycerols (Phospholipids)
• When one alcohol group of glycerol is esterified by a
phosphoric acid rather than by a carboxylic acid,
phosphatidic acid produced

• Phosphoacylglycerols (phosphoglycerides) are the second

most abundant group of naturally occurring lipids, and they
are found in plant and animal membranes
Waxes
• A complex mixture of esters of long-chain carboxylic
acids and alcohols
• Found as protective coatings for plants and animals
Sphingolipids
• Contain sphingosine, a long-
chain amino alcohol
sphingosine

• Found in plants and animals

• Abundant in nervous system

• Bares structural similarity to

phospholipids
Glycolipids
• Glycolipid: a compound in
which a carbohydrate is
bound to an -OH of the lipid

• In most cases, sugar is

either glucose or galactose
• many glycolipids are
derived from
ceramides
• Glycolipids with complex
carbohydrate moiety that
contains more than 3
sugars are known as
gangliosides (Fig. 8.8, p.
207)
Steroids
• Steroids: a group
of lipids that have
fused-ring
structure of 3 six-
membered rings,
and 1 five-
membered ring.
Sex Hormones
• Androgens: male sex hormones
• synthesized in the testes
• responsible for the development of male secondary
sex characteristics
• Testosterone
• Estrogens: female sex hormones
• synthesized in the ovaries
• responsible for the development of female secondary
sex characteristics and control of the menstrual cycle
(refer to Figure 8.9, p. 207)
Cholesterol
• The steroid of most interest in our discussion of
biological membranes is cholesterol
Biological Membranes
• Every cell has a cell membrane (plasma membrane)
• Eukaryotic cells also have membrane-enclosed organelles
(nuclei, mitochondria…etc)
• Molecular basis of membrane structure is in lipid
component(s):
• polar head groups are in contact with the aqueous
environment
• nonpolar tails are buried within the bilayer
• the major force driving the formation of lipid bilayers is
hydrophobic interaction
• the arrangement of hydrocarbon tails in the interior can be
rigid (if rich in saturated fatty acids) or fluid (if rich in
unsaturated fatty acids)
Lipid Bilayers
• The polar surface of
the bilayer contains
charged groups

• The hydrophobic
tails lie in the interior
of the bilayer
Biological Membranes
• Plant membranes have a higher percentage of
unsaturated fatty acids than animal membranes

• The presence of cholesterol is characteristic of

animal rather than plant membranes

• Animal membranes are less fluid (more rigid) than

plant membranes

• The membranes of prokaryotes, which contain no

appreciable amounts of steroids, are the most
fluid
Membrane Layers
• Both inner and outer
layers of bilayer contain
mixtures of lipids

• Compositions on inside
and outside of lipid
bilayer can be different

• This is what
distinguishes the layers
Effect of Double Bonds on the
Conformations of Fatty Acids
• Kink in hydrocarbon
chain

• Causes disorder in
packing against other
chains

• This disorder causes

greater fluidity in
membranes with cis-
double bonds vs......
saturated FA chains
Cholesterol reduces Fluidity
• Presence of cholesterol
reduces fluidity by
stabilizing extended
chain conformations of
hydrocarbon tails of FA

• Due to hydrophobic
interactions
Temperature Transition in Lipid Bilayer
• With heat, membranes become more disordered;
the transition temperature is higher for more rigid
membranes; it is lower for less rigid membranes

• Mobility of the lipid chains increases dramatically

(Biochemical Connections p. 212)
Membrane Proteins
• Functions: transport substances across membranes; act as receptor
sites, and sites of enzyme catalysis
• Peripheral proteins
• bound by electrostatic interactions
• can be removed by raising the ionic strength
• Integral proteins
• bound tightly to the interior of the membrane
• can be removed by treatment with detergents or ultrasonification
• removal generally denatures them
Proteins Can be Anchored to Membranes
• N-myristoyl- and S-
palmitoyl anchoring
motifs

• Anchors can be via N-

terminal gly

• Thioester linkage with

Cys
Fluid Mosaic Model
• Fluid: there is lateral motion of components in the
membrane;
• proteins, for example, “float” in the membrane and can
move along its plane

• Mosaic: components in the membrane exist side-by-side as

separate entities
• the structure is that of a lipid bilayer with proteins,
glycolipids, and steroids such as cholesterol
embedded in it
• no complexes, as for example, lipid-protein
complexes, are formed
Fluid Mosaic Model of Membrane Structure
Membrane Function: Membrane Transport
Passive transport
• driven by a concentration gradient
• simple diffusion: a molecule or ion moves through
an opening
• facilitated diffusion: a molecule or ion is carried
across a membrane by a carrier/channel protein
• Active transport
• a substance is moved against a concentration
gradient
• primary active transport: transport is linked to the
hydrolysis of ATP or other high-energy molecule; for
example, the Na+/K+ ion pump (Figure 8.24)
• secondary active transport: driven by H+ gradient
Passive Transport
• Passive diffusion of species (uncharged) across
membrane dependent on concentration, presence
of carrier protein
1˚ Active transport
• Movement of molecules against a gradient directly linked to
hydrolysis of high-energy yielding molecule (e.g. ATP)
Membrane Receptors
• Membrane receptors

• generally oligomeric
proteins

• binding of a
biologically active
substance to a
receptor initiates an
action within the cell
Lipid-Soluble Vitamins
• Vitamins are divided into two classes: lipid-soluble and water-soluble
Vitamin A
• Vitamin A (retinol) occurs only in the animal world
• Extensively unsaturated hydrocarbon (-carotene)
• Vitamin A is found in the plant world in the form of a
provitamin in a group of pigments called carotenes
• enzyme-catalyzed cleavage of -carotene followed by
reduction gives two molecules of vitamin A
Vitamin A
• The best understood role of Vitamin A is its participation in the
visual cycle in rod cells
• the active molecule is retinal (vitamin A aldehyde)
• retinal forms an imine with an -NH2 group of the
protein opsin to form the visual pigment called
rhodopsin
• the primary chemical event of vision in rod cells is
absorption of light by rhodopsin followed by
isomerization of the 11-cis double bond to the 11-trans
double bond
• (Biochemical Connections, p. 225)
Vitamin D
• A group of structurally
related compounds that
are involved in the
regulation of calcium and
phosphorus metabolism

• the most abundant

form in the
circulatory system is
vitamin D3
Vitamin E
• The most active of vitamin E is -tocopherol

• Vitamin E is an antioxidant; traps HOO• and ROO•

radicals formed as a result of oxidation by O2 of
unsaturated hydrocarbon chains in membrane
phospholipids
Vitamin K
• Vitamin K has an
important role in the
blood-clotting
process
• Long unsaturated
hydrocarbon side
consists of
repeating isoprene
units
Prostaglandins
• Prostaglandins: a family of compounds that have the 20-
carbon skeleton of prostanoic acid

• First detected in seminal fluid…from prostate

• The metabolic precursor is arachidonic acid (20 carbon

atoms: 4 double bonds)

• Production of prostaglandins from arachidonic acid occurs in

several steps.
Arachodonic Acid and Some
Prostoglandins
Leukotrienes
• Compounds also derived from arachidonic acid

• Found in white blood cells (leukocytes)

• Consists of 3 conjugated double bonds

• An important property is constriction of smooth

muscles, especially in the lungs
Leukotrienes (Cont’d)