Transcript Principles of BIOCHEMISTRY - Illinois State University

Chapter 9 - Lipids and Membranes
• Lipids are essential components of all living
organisms
• Lipids are water insoluble organic compounds
• They are hydrophobic (nonpolar) or
amphipathic (containing both nonpolar and
polar regions)
Fig 9.1 Structural relationships
of major lipid classes
Fatty Acids
• Fatty acids - R-COOH (R=hydrocarbon chain)
are components of triacylglycerols,
glycerophospholipids, sphingolipids
• Fatty acids differ from one another in:
(1) Length of the hydrocarbon tails
(2) Degree of unsaturation (double bond)
(3) Position of the double bonds in the chain
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Nomenclature of fatty acids
Most fatty acids have 12 to 20 carbons
Most chains have an even number of carbons
IUPAC nomenclature: carboxyl carbon is C-1
Common nomenclature: a,b,g,d,e etc. from C-1
Carbon farthest from carboxyl is w
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Structure and nomenclature of fatty acids
• Saturated - no C-C double bonds
• Unsaturated - at least one C-C double bond
• Monounsaturated - only one C-C double bond
• Polyunsaturated - two or more C-C double bonds
Double bonds in fatty acids
• Double bonds are generally cis
• Position of double bonds indicated by Dn, where n indicates
lower numbered carbon of each pair
• Shorthand notation example: 20:4D5,8,11,14
(total # carbons : # double bonds, D double bond positions)
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(a) Stearate (octadecanoate)
(b) Oleate (cis-D9-octadecenoate)
(c) Linolenate (all-cis-D9,12,15octadecatrienoate)
• The cis double bonds produce kinks
in the tails of unsaturated fatty acids
Fig. 9.3 Structures of three C18 fatty acids
Triacylglycerols
• Fatty acids are stored as neutral
lipids, triaclyglycerols (TGs)
Fats have 2-3 times the energy of
proteins or carbohydrates
• TGs are 3 fatty acyl residues
esterified to glycerol
• TGs are hydrophobic, stored in fat
cells (adipocytes)
Fig 9.5
Structure of a
triacylglycerol
Fig 9.9 Phospholipases hydrolyze phospholipids
Fig 9.10 Structure of an
ethanolamine plasmalogen
• Plasmalogens - C-1
hydrocarbon substituent
attached by a vinyl ether
linkage (not ester linkage)
Sphingolipids
• Sphingolipids - sphingosine is the backbone
abundant in central nervous system tissues
• Ceramides - fatty acyl group linked to C-2 of sphingosine by an
amide bond
• Sphingomyelins - phosphocholine attached to C-1 of ceramide
• Cerebrosides - glycosphingolipids with one monosaccharide
residue attached via a glycosidic linkage to
C-1 of ceramide
• Galactosylcerebrosides - a single b-D-galactose as a polar
head group
• Gangliosides - contain oligosaccharide chains with
N-acetyl-neuraminic acid (NeuNAc)
attached to aChapter
ceramide
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Fig 9.11
(a) Sphingosine
(b) Ceramides
(c) Sphingomyelin
Fig 9.12
• Structure of a
galactocerebroside
Fig 9.13 Ganglioside GM2
(NeuNAc in blue)
Steroids
• Classified as isoprenoids - related to 5-carbon isoprene
(found in membranes of eukaryotes)
• Steroids contain four fused ring systems: 3-six carbon rings
(A,B,C) and a 5-carbon D ring
• Ring system is nearly planar
• Substituents point either down (a) or up (b)
Fig 9.14
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Isoprene
Chapter 9
Fig 9.15
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Fig 9.15
Structures of
several steroids
Fig 9.15
Structures of
several steroids
Cholesterol
• Cholesterol modulates the fluidity of mammalian cell
membranes
• It is also a precursor of the steroid hormones and bile salts
• It is a sterol (has hydroxyl group at C-3)
• The fused ring system makes cholesterol less flexible than
most other lipids
Cholesterol esters
• Cholesterol is converted to cholesteryl esters for cell storage
or transport in blood
• Fatty acid is esterified to C-3 OH of cholesterol
• Cholesterol esters are very water insoluble and must be
complexed with phospholipids or amphipathic proteins for
transport
Fig 9.17 Cholesteryl ester
Waxes
• Waxes are nonpolar esters of long-chain fatty acids and
long chain monohydroxylic alcohols
• Waxes are very water insoluble and high melting
• They are widely distributed in nature as protective
waterproof coatings on leaves, fruits, animal skin, fur,
feathers and exoskeletons
Fig 9.18 Myricyl palmitate, a wax
Eicosanoids
• Eicosanoids are oxygenated derivatives of C20
polyunsaturated fatty acids (e.g. arachidonic acid)
• Prostaglandin E2 - can cause constriction of blood vessels
• Thromboxane A2 - involved in blood clot formation
• Leukotriene D4 - mediator of smooth-muscle contraction
and bronchial constriction seen in asthmatics
• Aspirin alleviates pain, fever, and inflammation by inhibiting
cyclooxygenase (COX), an enzyme critical for the synthesis
of prostaglandins. (NSAID family of compounds)
Fig 9.19 Arachidonic acid and eicosanoid derivatives
Lipid vitamins
• Vitamins A,D,E,
and K are
isoprenoid
derivatives
Vitamin E
Biological Membranes Are Composed
of Lipid Bilayers and Proteins
• Biological membranes define the external
boundaries of cells and separate cellular
compartments
• A biological membrane consists of proteins
embedded in or associated with a lipid bilayer
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Several important functions of membranes
• Some membranes contain protein pumps for ions or small
molecules
• Some membranes generate proton gradients for ATP
production
• Membrane receptors respond to extracellular signals and
communicate them to the cell interior
Lipid Bilayers
• Lipid bilayers are the structural basis for all biological
membranes
• Noncovalent interactions among lipid molecules make them
flexible and self-sealing
• Polar head groups contact aqueous medium
• Nonpolar tails point toward the interior
Fig 9.21 Membrane lipid and bilayer
Fluid Mosaic Model of Biological Membranes
• Fluid mosaic model - membrane proteins and
lipids can rapidly diffuse laterally or rotate within
the bilayer (proteins “float” in a lipid-bilayer sea)
• Membranes: ~25-50% lipid and 50-75% proteins
• Lipids include phospholipids, glycosphingolipids,
cholesterol (in some eukaryotes)
• Compositions of biological membranes vary
considerably among species and cell types
Fig 9.22 Structure of a typical
eukaryotic plasma membrane
Lipid Bilayers and Membranes Are Dynamic Structures
Fig 9.23 (a) Lateral diffusion is very rapid
(b) Transverse diffusion (flip-flop) is very slow
Fig 9.25 Freeze-fracture electron microscopy,
distribution of membrane proteins
Fig 9.22 Structure of a typical
eukaryotic plasma membrane
Three Classes of Membrane Proteins
(1) Integral membrane proteins
Contain hydrophobic regions embedded in the lipid bilayer
• Usually span the bilayer completely
(2) Peripheral membrane proteins
• Associated with membrane through charge-charge or hydrogen
bonding interactions to integral proteins or membrane lipids
• More readily dissociated from membranes than covalently
bound proteins
• Change in pH or ionic strength often releases these proteins
(3) Lipid-anchored membrane proteins
• Tethered to membrane through a covalent bond to a lipid
Fig 9.22 Structure of a typical
eukaryotic plasma membrane
Membrane Transport
• Three types of integral membrane protein
transport:
(1) Channels and pores
(2) Passive transporters
(3) Active transporters
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Table 9.3 Characteristics of membrane transport
Pores and Channels
• Pores and channels are transmembrane proteins with a
central passage for ions and small molecules
• Solutes of appropriate size, charge, and molecular structure
can diffuse down a concentration gradient
• Process requires no energy
• Central passage allows
molecules and ions of
certain size, charge and
geometry to transverse
the membrane.
• Figure 9.30
Passive Transport
• Passive transport (facilitated diffusion) does not require an
energy source
• Protein binds solutes and transports them down a
concentration gradient
Types of passive transport systems
• Uniport - transporter carries only a single type of solute
• Some transporters carry out cotransport of two solutes,
either in the same direction (symport) or in opposite
directions (antiport)
Fig 9.31
• Types of passive transport
(a) Uniport
(b) Symport
(c) Antiport
Fig 9.32 Kinetics of passive transport
• Initial rate of
transport
increases until a
maximum is
reached
(site is saturated)
Active Transport
• Transport requires energy to move a solute up its
concentration gradient
• Transport of charged molecules or ions may result
in a charge gradient across the membrane
Types of active transport
• Primary active transport is powered by a
direct source of energy as ATP, light or
electron transport
• Secondary active transport is driven by an
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ion concentration gradient
Fig 9.34 Secondary active transport in E. coli
• Oxidation of Sred
generates a
transmembrane
proton gradient
• Movement of H+
down its gradient
drives lactose
transport (lactose
permease)
Fig 9.35 Secondary active transport
in animals: Na+-K+ ATPase
• Na+ gradient (Na+-K+ATPase) drives glucose transport
Endocytosis and Exocytosis
• Cells import/export molecules too large to be
transported via pores, channels or proteins by:
• Endocytosis - macromolecules are engulfed by
plasma membrane and brought into the cell
inside a lipid vesicle
• Exocytosis - materials to be excreted from the
cell are enclosed in vesicles that fuse with the
plasma membrane
Transduction of Extracellular Signals
• Specific receptors in plasma membranes
respond to external chemicals (ligands) that
cannot cross the membrane: hormones,
neurotransmitters, growth factors
• Signal is passed through membrane protein
transducer to a membrane-bound effector
enzyme
• Effector enzyme generates a second
messenger which diffuses to intracellular target
Fig 9.37 General mechanism of signal
transduction across a membrane
Fig 9.43
• Summary of
the adenyl
cyclase
signaling
pathway