Fundamentals of
Biochemistry
Fourth Edition
Donald Voet • Judith G. Voet •
Charlotte W. Pratt
Chapter 9
Lipids and Biological Membranes
Copyright © 2013 by John Wiley & Sons, Inc. All rights reserved.
There are several classifications of lipids.
• Fatty Acids
Lipids (Fats) –
• Triacylglycerols Biological
molecules that are
• Glycerophospholipids soluble in
nonpolar solvents
• Sphingolipids and
poorly soluble in
water
• Isoprenoids
– Cholesterol
© 2014 John Wiley & Sons, Inc. All rights reserved.
Fatty acids are long-chain
hydrocarbons
• Amphiphiles
• Polar head group:
carboxylic acids
• Nonpolar tail:
hydrocarbon chain
• Fatty acids can be
saturated with
hydrogen, unsaturated,
or polyunsaturated.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Common Biological Fatty Acids
Triacylglycerols (Triglycerides) Contain 3x Esterified
Fatty Acids
R1, R2 and R3 are fatty
acid chains
Triacylglycerols function as energy reservoirs in animals.
Fats provide about six times the metabolic energy of an
equal weight of hydrated glycogen.
Adipocytes are specialized cells for the synthesis and
storage of triacylglycerols.
Glycerophospholipids
• R1 and R2 are
fatty acid
chains
• X = functional
group
Major lipid components of biological membranes.
Amphiphilic molecules with nonpolar aliphatic (hydrocarbon) “tails”
and polar phosphoryl-X “heads.”
© 2014 John Wiley & Sons, Inc. All rights reserved.
There are three common head
groups on glycerophospholipids
Notice
similarities
Phospholipases cleave phospholipids at specific
sites.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Plasmalogens Contain an Ether Linkage
Replaces C1 Ester
Plasmalogens are glycerophospholipids in which the C1 substituent of
the glycerol moiety is linked via unsaturated ether linkage rather than
through an ester linkage.
Sphingolipids
• Sphingolipids are also major membrane components and have
considerable physiological and medical significance.
• Instead of using glycerol as a backbone, sphingolipids use
sphingosine as a backbone.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Sphingomyelins
Most common sphingolipids with either a Phosphocholine or
a phosphoethanolamine head group.
Sphingomyelin is found in the myelin sheath around nerves
Cerebroside has monosaccharides
as head groups
• A cerebroside is a
sphingolipid with a
monosaccharide
head group.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Ganglioside is a sphingolipid with oligosaccharides as head groups
Gangliosides are primarily
components of cell-surface
membranes and constitute a
significant fraction (6%) of
brain lipids.
Their complex carbohydrate
head groups, which extend
beyond the surfaces of cell
membranes, act as specific
receptors for certain pituitary
glycoprotein hormones.
Gangliosides are also
receptors for certain bacterial
protein toxins such as cholera
toxin.
Gangliosides are specific
determinants of cell-cell
recognition, important role in
the growth and differentiation
of tissues as well as in
carcinogenesis.
Cholesterol
• Cholesterol is the most abundant steroid in animals
• Major component of animal plasma membranes
• Fused ring system provides it with greater rigidity than other lipids
• Metabolic precursor of steroid hormones
• Amphiphilic character
Cholesterol is the metabolic precursor of steroid
hormones in mammals
Cortisol affects carbohydrate,
protein, and lipid metabolism.
Aldosterone regulate the excretion
of salt and water by the kidneys.
Testosterone is male sex hormone.
estrogen is female sex hormone.
Vitamin D Regulates Ca2+ Metabolism.
Vitamin D various forms are sterol derivative hormones in which the
steroid B ring is disrupted between C9 and C10.
Vitamins D2 and D3 are inactive; the active forms are produced through their enzymatic
hydroxylation (addition of an OH group) carried out by the liver (at C25) and by the
kidney (at C1)
Active vitamin D increases serum [Ca2+] by
promoting the intestinal absorption of
dietary Ca2+. This increases the deposition of
Ca2+ in bones and teeth.
Other Lipids Perform a Variety of Metabolic Roles
Vitamin K is a lipid synthesized by plants (as The isoprenoid ubiquinone (also known as
phylloquinone) and bacteria (as menaquinone) coenzyme Q) is reversibly reduced and
oxidized in the mitochondrial membrane
About half of the vitamin K daily requirement for humans is supplied by intestinal bacteria.
It participates in the carboxylation of Glu residues in some of the proteins involved in blood
clotting. Vitamin K deficiency prevents this carboxylation, and the resulting inactive clotting
proteins lead to excessive bleeding.
Other Lipids Perform a Variety of Metabolic Roles
Vitamin E is a highly hydrophobic molecule which is incorporated into
cell membranes, where it functions as an antioxidant that prevents
oxidative damage to membrane proteins and lipids.
Vitamin A or retinol is derived mainly
from plant products such as β- carotene.
Retinal functions as the eye’s photoreceptor
at low light intensities.
Eicosanoids Are Derived from Arachidonic Acid.
Eicosanoids act at very low concentrations and are involved in the production of pain
and fever, and in the regulation of blood pressure, blood coagulation, and reproduction.
Micelles
In aqueous solutions, amphiphilic molecules such as soaps and detergents
(single-
tailed lipids) aggregate forming micelles.
Lipid Bilayers
In aqueous solutions, phospholipids (glycerophospholipids or sphingomyelins) can form
liposomes which are self-sealing solvent-filled vesicles made of only a single bilayer.
Characteristics of the Lipid Bilayer
• Fluid
– No clearly defined
geometry
– Head groups move
up, down
– Hydrocarbon tails
wave
• Asymmetric A lipid bilayer
– Different lipids are
found in each “leaflet”
© 2014 John Wiley & Sons, Inc. All rights reserved.
Diffusion in membranes differs according to direction
Fluidity of Lipid Bilayer is Temperature Dependent
Below transition temperature, lipid bilayer undergoes a sort of phase change and
becomes a gel-like solid.
The fluidity of a lipid bilayer decreases with the chain length and the degree of
saturation of its component fatty acid residues for the same reasons that the
melting points of fatty acids increase with these quantities.
Proteins associate with membranes in different ways
Some lipids anchor proteins in the membrane.
© 2014 John Wiley & Sons, Inc. All rights reserved.
Integral Membrane Proteins
Membrane proteins catalyze chemical reactions, mediate the flow of nutrients and wastes
across the membrane, and participate in relaying information about the extracellular
environment to various intracellular components.
Integral or intrinsic proteins associate tightly with membranes through hydrophobic effects
and can be separated from membranes only by treatment with agents that disrupt membranes.
polar
hydrophobic
polar residues
X-Ray structure of the integral membrane protein
aquaporin-0 (AQP0) in association with lipids. Human erythrocyte glycophorin
A
Membrane proteins can span the bilayer
Bacteriorhodopsin Beta Barrel
20 amino acids/helix 8 strands minimum
Transmembrane segments of integral proteins consist of either alpha helix or beta
sheets.
β Barrels occur in porins, which are channel-forming proteins that permit the entry of
small polar solutes such as nutrients.
Lipids can be covalently linked to proteins in a
variety of ways
Myristoylation Palmitoylation Prenylation
Lipid-linked proteins come in three varieties: prenylated proteins, fatty acylated proteins (myristic and
palmitic acids), and glycosylphosphatidylinositol-linked proteins. They can be located in a number of
subcellular compartments, including the cytosol, endoplasmic reticulum, plasma membrane, and the
nucleus.
Peripheral or Extrinsic Proteins
Peripheral or extrinsic proteins, unlike integral membrane proteins or lipid linked
proteins, can be dissociated from membranes by relatively mild procedures that leave
the membrane intact, such as exposure to high ionic strength salt solutions or pH
changes. Peripheral proteins do not bind lipid and, once purified, behave like water-
soluble proteins. Cytochrome c is a peripheral membrane protein that is associated with
the outer surface of the inner mitochondrial membrane. At physiological pH, cytochrome
c is cationic and can interact with negatively charged phospholipids such as
phosphatidylserine and phosphatidylglycerol.
© 2014 John Wiley & Sons, Inc. All rights reserved.
The Fluid Mosaic Model
Membrane structure is defined by the fluid mosaic model. A key element of the model
is that integral proteins can diffuse laterally in the lipid matrix. Membrane proteins float
in a sea of lipids and do not transverse the bilayer.
Membranes Have Asymmetric
Phospholipid Distribution
