Transcript Lipids and Proteins Are Associated in Membranes Chapter 8

Chapter 8
Lipids and Proteins Are Associated in Membranes

The Definition of a Lipid
- Lipids are marginally soluble in water but readily soluble in organic solvents
 Fats and oils are typical lipids in terms of their solubility
- Lipids are a mixed bag of compounds that share some properties based on structural
similarities, mainly a preponderance of nonpolar groups
 Open-chain compounds with polar head groups and long nonpolar tails
(fatty acids, triacylglycerols, sphingolipids, phosphoacylglycerols, and glycolipids)
 Fused-ring compounds, the steroids (e.g., cholesterol)
Dept. of Chemical Engineering
Chapter 8
Lipids and Proteins Are Associated in Membranes
- Biological lipids are a chemically diverse group of compounds, the common and
defining feature of which is their insolubility in water
- The biological functions of the lipids are as diverse as their chemistry
 Fats and oils are the principal stored forms of energy in many organisms
 Phospholipids and sterols are major structural elements of biological membranes
 Other lipids play crucial roles as enzyme cofactors, hydrophobic anchors for proteins,
“chaperones” to help membrane proteins fold, and emulsifying agents in the digestive
tract
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Chapter 8
The Chemical Natures of the Lipid Types

Fatty Acids
- Fatty acids are carboxylic acids with hydrocarbon chains ranging from 4 to 36 carbons
long (C4 to C36)
- A simplified nomenclature for fatty acids specifies the chain length and number of
double bonds, separated by a colon: e.g., 16-carbon saturated palmitic acid  16:0
 20-carbon fatty acid with one double bond between C-9 and C-10 and another
between C-12 and C-13; 20:2(9,12)
- The most commonly occurring fatty acids have even numbers of carbon atoms in an
unbranched chain of 12 to 24 carbons
- In nearly all naturally occurring unsaturated fatty acids, the double bonds are in the cis
configuration
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Chapter 8
Lipids and Proteins Are Associated in Membranes
Dept. of Chemical Engineering
Chapter 8
The Chemical Natures of the Lipid Types

Fatty Acids
- Trans fatty acids are produced during hydrogenation of fish or vegetable oil
 Diets high in trans fatty acids correlate with increased blood levels of LDL (bad
cholesterol) and decreased HDL (good cholesterol)
 French fries, doughnuts, and cookies tend to be high in trans fatty acid
- The physical properties of the fatty acids are largely determined by the length and
degree of unsaturation of the hydrocarbon chain
 The nonpolar hydrocarbon chain accounts for the poor solubility in water
 The longer the fatty acyl chain and the fewer the double bonds, the lower is
solubility in water
- Melting points are also strongly influenced by the length and degree of unsaturation
of the hydrocarbon chain
 Saturated FA: waxy, unsaturated FA: oily liquid  Different degrees of packing
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Chapter 8
The Chemical Natures of the Lipid Types
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Chapter 8
The Chemical Natures of the Lipid Types
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Triacylglycerols
- The simplest lipids constructed from fatty acids are the triacylglycerols, also referred to
as triglycerides, fats, or neutral fats
 Triacylglycerols are composed of three fatty acids each in ester linkage with a single
glycerol
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Chapter 8
The Chemical Natures of the Lipid Types
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Triacylglycerols
- Triacylglycerols form a separate phase of microscopic, oily droplets in the cytosol,
serving as depots of metabolic fuel
 Adipocytes (fat cells) in vertebrates and seeds of plants store large amounts of
triacylglycerols as fat droplets
 Adipocytes and germinating seeds contain lipases, enzymes that catalyze the
hydrolysis of stored triacylglycerols
Stored oils
Guinea pig adipocytes
Cell from a seed of the
plant Arabidopsis
Dept. of Chemical Engineering
Chapter 8
The Chemical Natures of the Lipid Types
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Triacylglycerols
- Most natural fats, such as those in vegetable oils, dairy products,
and animal fat, are complex mixtures of simple and mixed
triacylglycerols
 These contain a variety of fatty acids differing in chain length
and degree of saturation
- The hydrolysis reactions can take place outside organisms with
acids or bases as catalysts
 The products of the reaction, called saponification, are
salts of the fatty acids (soaps)
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Chapter 8
The Chemical Natures of the Lipid Types
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Triacylglycerols
- There are two advantages in using triacylglycerols as stored fuels, rather than
polysaccharides such as glycogen and starch
1) Oxidation of tryacylglycerols (~ 9 kcal/g) yields more than twice as much energy as
the oxidation of carbohydrates (~ 4 kcal/g)
2) The organism that carries fat as fuel does not have to carry the extra weight of
water of hydration that is associated with stored polysaccharides ( 2g per g of PS)
- Humans have fat tissues (composed primarily of adipocytes) under the skin, in the
abdominal cavity, and in the mammary glands
e.g., Carbohydrates such as glucose and glycogen do offer advantages as quick sources of
metabolic energy, one of which is their ready solubility in water
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Chapter 8
The Chemical Natures of the Lipid Types
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Triacylglycerols
- In some animals, triacylglycerols stored under the skin serve not only as energy stores
but as insulation against low temperature
e.g., Seals, walruses, and penguins are amply padded with triacylglycerols
- In hibernating animals (e.g., bears), the huge fat reserves accumulated before
hibernation serve the dual purposes of insulation and energy storage
Dept. of Chemical Engineering
Chapter 8
The Chemical Natures of the Lipid Types
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Phosphoacylglycerols
- Glycerophospholipids, also called phosphoacylglycerols, are membrane lipids in which
two fatty acids are attached in ester linkage to the first and second carbons of glycerol,
and a highly polar or charged group is attached through a phosphodiester linkage to the
third carbon
- Glycerophospholipids are named as derivatives of the parent compound, phosphatidic
acid, according to the polar alcohol in the head group
 e.g., phosphatidylcholine and phosphatidylethanolamine have choline and
ethanolamine in their polar head groups, respectively
 The phosphate group bears a negative charge at neutral pH, while the polar alchol
may be negatively charged, neutral, or positively charged
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The Chemical Natures of the Lipid Types
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Phosphoacylglycerols
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Chapter 8
The Chemical Natures of the Lipid Types
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Waxes and sphingolipids
- Biological waxes are esters of long-chain (C14 to C36) saturated and unsaturated fatty
acids with long-chain (C16 to C30) alchols
 Their melting points (60-100 oC) are generally higher than those of triacylglycerols
- Waxes serve functions related to their water-repellent properties
 Certain skin glands of vertebrates secrete waxes to protect hair and skin and keep it
pliable, lubricated, and waterproof
 Birds, particularly waterfowl, secrete waxes from their preen glands to keep their
feathers water-repellent
 The shiny leaves of many tropical plants are coated with a thick layer of waxes
- Myricyl cerotate, produced by the Brazilian wax palm, is
extensively used in floor wax and automobile wax
- Cetyl palmitate, produced by whales, has been used as the
component of cosmetics
Dept. of Chemical Engineering
Chapter 8
The Chemical Natures of the Lipid Types
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Waxes and sphingolipids
- Sphingolipids also have a polar head group and two nonpolar tails, but unlike
glycerophospholipids and galactolipids they contain no glycerol
 Sphingolipids are composed of one molecule of the long-chain amino alcohol
sphingosine or one of its derivatives and a polar head group
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Chapter 8
The Chemical Natures of the Lipid Types
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Waxes and sphingolipids
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Chapter 8
The Chemical Natures of the Lipid Types
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Glycolipids
- If a carbohydrate is bound to an alcohol group of a lipid by a glycosidic linkage, the
resulting compound is a glycolipid
 Glycosphingolipids (neutral glycolipids): Cerebrosides having a single sugar linked to
ceramide + Globosides having two or more sugars
 Gangliosides have oligosaccharides as their polar head groups and one or more
residues of N-acetylneuraminic acid (Neu5Ac), a sialic acid, at the termini
Dept. of Chemical Engineering
Chapter 8
The Chemical Natures of the Lipid Types
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Steroids
- Steoids have the same general structure: a fused-ring system consisting of three sixmembered rings and one five-membered ring
- Cholesterol, the major steroid in animal tissues, is amphipathic, with a polar head group
(the hydroxyl group at C-3) and a nonpolar hydrocarbon body, about as long as a 16carbon fatty acid in its extended form
- Cholesterol is a precusor of other steroids and of vitamin D3
 However, it’s harmful when present in excess in the blood
(altherosclerosis)
- Bile acids are polar derivatives of cholesterol that act as
detergents in the intestine, emulsifying dietary fats
to make them more readily accessible to digestive lipases
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Chapter 8
Biological Membranes
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The structure of lipid bilayers
- The molecular basis of the membrane’s structure lies in its lipid and protein
components
 Lipid bilayers depends on hydrophobic interactions
 The protein component of a membrane can make up from 20% to 80%
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Chapter 8
Biological Membranes
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The structure of lipid bilayers
- The bilayer’s fluidity depends on its composition
 Bulkier molecules tend to occure in the outher layer
 Saturated fatty acids and cholesterol lead to close packing of molecules in the bilayer
 Unsaturated fatty acids cause disorder in the packing of the chains, resulting in
greater fluidity in the bilayer
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The Kinds of Membrane Proteins
- Peripheral proteins on the membrane and integral proteins within the lipid bilayer
 Peripheral proteins are bound to the charged head groups of the membrane by polar
interactions, electrostatic interactions, or both
 When a protein spans the membrane, it is often in the form of an α-helix or β-sheet,
which can minimize contact of the polar parts of the peptide backbone with the
nonpolar lipids
- Membrane proteins have a variety of functions
e.g., Transport proteins, receptor proteins, enzymes
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The Fluid-Mosaic Model of Membrane Structure
- Fluid-mosaic model is the most widely accepted description of biological membranes
 The term “mosaic” implies that the two components (lipid and protein) exist die by
side without forming intermediates
 The term “fluid mosaic” implies that the same sort of lateral motion occurs in
membrane (the proteins float in the bilayer and can move along the plane of the
membrane)
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The Functions of Membrane
- Transport
 Membranes are semipermeable barriers and transport through the membrane can
involve the lipid bilayer as well as the membrane proteins
- Catalysis
 The enzymatic reaction takes place on the membrane
- Receptor property
 Proteins bind specific biologically important substances that trigger biochemical
responses in the cell
Dept. of Chemical Engineering
Chapter 8
The Functions of Membrane
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Transport
- In passive transport, a substance moves from a region of higher concentration to one
of lower concentraion
 The substance moves depending on a concentration gradient, and the cell does not
expend energy
- In active transport, a substance moves from a region of lower concentration to one of
higher conentraion, requiring the cell to expend energy
- The process of passive transport can be divided into two categories
 In simple diffusion, a molecule moves directly through the
membrane (small, uncharged molecules such as O2, N2, and CO2)
 In facilitated diffusion, a molecuel passively moves through a
membrane using a carrier protein (e.g., glucose transport by
glucose permease)
Dept. of Chemical Engineering
Chapter 8
The Functions of Membrane
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Transport
- Active transport is characterized by the presence of a carrier protein and the need for
an energy source to move solutes against a gradient
 In primary active transport, the movement of molecules is directly linked to the
hydrolysis of a high-energy molecule, such as ATP.
 In the secondary active transport, the protein uses the energy indirectly.
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The Functions of Membrane
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Receptors
- Receptors are often large oligomeric proteins
 Effects of some biologically active substances are due to the binding of the
substance to a protein receptor site on the exterior of the cell
 E.g, low-density lipoprotein (LDL), the principal carrier of cholesterol in the blood
Oversupply of cholesterol
Binding to the receptor
Receptor-mediated endocytosis
Recycling to the surface
Inhibition of the synthesis
of LDL receptor
High level of cholesterol
in blood
Atherosclerosis
Heart attacks
Strokes
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Chapter 8
Lipid-Soluble Vitamins and Their Functions
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Vitamin A
- Vitamin A (retinol) in its various forms functions as a hormone and as the visual
pigment of the vertebrate eye
 Vitamin A derivative retinoic acid regulates gene expression in the development of
epithelial tissue, including skin
 The vitamin A derivative retinal is the pigment that initiates the response of rod and
cone cells of the retina to light, producing a neuronal signal to the brain
- In vertebrates, -carotene, the pigment that gives carrots, sweet potatoes, and other
yellow vegetables their characteristic color, can be enzymatically converted to vitamin
A
 Deficiency of vitamin A  dryness of the skin, eyes, and mucous membranes;
retarded development and growth; and night blindness
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Chapter 8
Lipid-Soluble Vitamins and Their Functions
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Chapter 8
Lipid-Soluble Vitamins and Their Functions

Vitamin D
- The several forms of vitamin D play a major role in the regulation of calcium and
phosphorus metabolism
 Vitamin D3, called cholecalciferol, is formed in the skin from 7-dehydrocholesterol in
a photochemical reaction driven by the UV component of sunlight
- Vitamin D3 is not itself biologically active, but it is converted by enzymes in the liver
and kidney to 1,25-dihydroxycholecalciferol, a hormone that regulates calcium uptake in
the intestine and calcium levels in kidney and bone
 Deficiency of vitamin D leads to defective bone formation and the disease rickets
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Lipid-Soluble Vitamins and Their Functions
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Vitamin E
- Vitamin E is the collective name for a group of closely related lipids called tocopherols,
all of which contain a substituted aromatic ring and a long isoprenoid side chain
 Tocopherols are biological antioxidants.
 The aromatic ring reacts with and destroys the most reactive forms of oxygen
radicals and other free radicals, protecting unsaturated fatty acids from oxidation and
preventing oxidative damage to membrane lipids, which can cause cell fragility
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Lipid-Soluble Vitamins and Their Functions
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Vitamin K
- The aromatic ring of vitamin K undergoes a cycle of oxidation and reduction during
the formation of active prothrombin, a blood plasma protein essential in blood clot
formation
 Vitamin K deficiency slows blood clotting, which can be fatal
 Two well-known anticoagulants, dicumarol and warfarin, are vitamin K antagonists
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Chapter 8
Prostaglandins and Leukotrienes
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Eicosanoids
- Eicosanoids are paracrine hormones, substances that act only on cells near the point of
hormone synthesis
- All eicosanoids are derived from arachidonic acid, the 20-carbon polyunsaturated fatty acid
 There are three classes of eicosanoids: prostaglandins, thromboxanes, and leukotrienes
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Chapter 8
Prostaglandins and Leukotrienes
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Eicosanoids
- Prostaglandins (PG) such as PGE1 and PGE2 contain a five-carbon ring
originating from the chain of arachidonic acid
 They affect a wide range of cellular and tissue functions
e.g., Some PGs stimulate contraction of the smooth muscle; others affect
blood flow to specific organs, and they may elevate body temperature
(producing fever) and cause inflammation and pain
- Thromboxanes have a six-membered ring containing an ether, which is
produced by platelets and act in the formation of blood clots and the reduction
of blood flow to the site of a clot
 The nonsteroidal antiinflammatory drugs (NASAIDs) - e.g., aspirin,
ibuprofen – inhibit the enzyme PG H2 synthesase, which catalyze an early step
in the pathway from arachidonate to prostaglandins and thromboxanes
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Chapter 8
Prostaglandins and Leukotrienes
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Eicosanoids
- Leukotrienes, first found in leukocytes, contain three conjugated double bonds
 Leukotriene D4, derived from leukotriene A4, induces contraction of the
muscle lining the airways to the lung
- Overproduction of leukotrienes causes asthmatic attacks,
 Drugs that inhibit the synthesis of leukotriene C are now being used in the
treatment of asthma, as are other drugs designed to block leukotriene
receptors
Leukotriene C
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