18-1 principles and applications of inorganic, organic, and biological chemistry denniston, topping,...
TRANSCRIPT
18-1
Principles and Applications ofInorganic, Organic, and
Biological ChemistryDenniston, Topping, and Caret
4th edChapter 18
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Power Point to Accompany
18-2
18.1 Lipids• Lipids- a collection of organic
molecules united by solubility in nonpolar solvents.
• Varying chemical composition
• Four main groups
18-3
Main Groups1. Fatty acids
Saturated and unsaturated
2. Glycerides
Contain glycerol (HOCH2CHOHCH2OH)
3. Nonglycerides
Sphingolipids, steroids, waxes
4. Complex lipids
lipoproteins
18-4
Lipid Functions• As an energy source, lipids provide 9
kcal of energy per gram.• Triglycerides provide energy storage in
adipocytes.• Phosphoglycerides, sphingolipids, and
steroids are part of cell membranes.• Steroid hormones are critical intercell
messengers.• Lipid soluble vitamins (A, E, D, E)• Provide shock absorption and
insulation.
18-5
18.2 Fatty AcidsLauric acid: a typical saturated fatty acid with
12 carbons in the chain (in salt form)Fatty acid: 12-20 carbons, even # carbons, no
branching, nonpolar carbon chain, polar COO- group (as anion).
CH3
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
C
O
O
Nonpolar hydrophobic tail“Polar” hydrophilic head
2
18-6
Fatty Acids-2An unsaturated fatty acid has one or more
carbon-carbon double bonds in the chain. The first double bond is usually at the ninth carbon. The double bonds are not conjugated and are usually cis.
C
O
OCH2CH2
C C
CH2
CH2
CH2
CH2
CH2
CH2
HH
CH2
CH2
CH2
CH2
CH3
Palmitoleic acid, salt form
Cis double bond results in a bent chain and lower mp.
2
18-7
Fatty Acids-3Stearic 18:0 (# of C and double
bonds)
CH3(CH2)16COOH
Palmitoleic 16:19 (9 position of double bond)
CH3(CH2)5CH=CH (CH2)7COOH
Linolenic 18:29,12
CH3(CH2)4CH=CHCH2CH=CH(CH2)7CO
Arachidonic 20:4,8,11,14
CH3(CH2)3(CH2CH=CH)4(CH2)3 COOH
18-8
Fatty Acid PropertiesMp increases with carbon number.
Mp of saturated acid is higher than an unsaturated acid of same carbon number.
cis double bond prevents good alignment of molecules in unsaturated fatty acids. Lowers mp relative to saturated or trans acid.
18-9
Fatty Acid Reactions-1Esterification
R CO
OH OH R' O R'R CO
+ +H+
warm H2O
Acid Hydrolysis
R CO
OH OH R'O R'R CO
++H+
warmH2O
18-10
Fatty Acid Reactions-2Saponification
R CO
ONa OH R'O R'R CO
++NaOH
Hydrogenation of Double Bonds
2 H2, Ni
CH3 CH2 C
O
OH16
CH2CH CH CH2 C
O
OHCH3 CH2 CH CH4 7
18-11
Eicosanoids: Prostaglandins, etc.
Arichadonic acid (20 carbons) is the eichosanoid presursor.
COO-
arachadonic acidProstaglandins have hormonelike
activity.
In PGF2, PG stands for prostaglandin; F for a particular group with OH on C-9; and the 2 indicates two double bonds.
18-12
Prostaglandin Function• Stimulation of smooth muscle
• Regulation of steroid biosynthesis
• Inhibition of gastric secretion
• Inhibition of hormone-sensitive lipases
• Inhibition of platelet aggregation
• Stimulation of platelet aggregation
• Regulation of nerve transmission
• Sensitization to pain
• Mediation of inflammatory response
18-13
Aspirin and ProstaglandinsAspirin inhibits prostaglandin synthesis
by acylating cyclooxygenase, an enzyme necessary for prostaglandin synthesis.
arachadonic acid
PGH2
cyclooxygenase-NH2
+
cyclooxygenase-NH CO
CH3NH
O CO
CH3
COO-
OH
COO-
Acylated enzyme
18-14
18.3 Glycerides: TriacylglycerolsWhen all three alcohol groups of glycerol
form esters with fatty acids a neutral triacylglycerol (triglyceride) is formed.
Triglycerides serve as energy storage in adipose cells.
CH2
CH
CH2
O
O
O CO
CO
CO
R1
R2
R3
Fatty acid chains
Glycerolpart
18-15
PhosphoglyceridesHave hydrophobic and hydrophilic
domains.
Structural components of membranes
Emulsifying agents
Suspended in water they spontaneously rearrange into ordered structures
Hydrophobic group to center
Hydrophilic group to water
(Basis of membrane structure)
18-16
Phosphoglycerides-2When the third OH of glycerol is esterified to a
phosphoric acid or a phosphoric acid ester instead of a carboxylic acid, a phosphoacylglycerol results.
CH2
CH
CH2
O
O
O PO
CO
CO
R1
R2
OH
O
Phosphatidic acidCH2
CH
CH2
O
O
O PO
CO
CO
R1
R2
OR
OPhosphatidic ester
18-17
Phosphatidyl esters, egs.
CH2
CH
CH2
O
O
O PO
CO
CO
R1
R2
OR
O
R=CH2CH2NH3
+
phosphatidylethanolamine
CH2CH2N(CH3)3+
phosphatidylcholine(lecithin)
Lecithin has a polar head and is amphipathic. It is the major phospholipid in pulmonary surfactant and an emulsifying agent.
18-18
18.4 Nonglyceride Lipids: Sphingolipids
These lipids are based on sphingosine, are found in plants and animals, and are common in the nervous system.
CH CH CH2 CH3
CH OH
CH NH2
CH2OH
12
18-19
Sphingolipids-2
CH CH CH2 CH3
CH OH
CH NH
CH2OH
12
CO
R1
A ceramideN-acylsphingosine
CH CH CH2 CH3
CH OH
CH NH
CH2O
12
OR1
P OO
CO
CH2CH2N+(CH3)3
A sphingomyelinEssential to cerebral functionand nerve transmission.
18-20
Glycolipids or GlycosphingolipidsFrequently a glucose or galactose is bound to
the primary alcohol of a ceramide. The compound is called a cerebroside. These compounds are found in the cell membranes of nerve and brain cells.
OCH2OH
HH
OHH
OH
OH
HH
OCH CH CH2
CH3CHOH
CHNH
CH2 12
C O
R1A cerebroside
18-21
Glycolipids-2: GangliosidesGangliosides have oligosaccharide
groups with one or more sialic acid (N-acetylnuraminic acid) residues attached. Names include M, D, T (# residues) and subscripts for number of sugars attached to the ceramide.
See the next slide for the structure of a ganglioside associated with Tay-Sachs an autosomal recessive disease resulting in neurological deterioration.
18-22
Gangleoside GM2
OCH2OH
O
O
OH
O
SphOCH2OH
OH
OH
OOCH2OH
OH
OH
NHC OCH3
OR
NH
OH
COO-C
O
CH3 R = CH OHCH OHCH2OH
Sph=ceramide
18-23
Sphingolipid Storage Diseases
Disease Sympt. Sph. Lip Enzyme
Tay-Sachs Blindness,
muscle weakenss
Ganglioside
GM2
-hexose-
aminidaseA
Gaucher’s Liver and spleen enlarge, MR
Glucocer-
ebroside
-glucos-
idase
Krabbe’s demyelation,
MR
Galactocer-
ebroside
-galactos-
idase
Nieman-Pick
MR Sphingo-
myelin
Sphingomy-
elinase
18-24
SteroidsSteroids are synthesized from the five
carbon isoprene unit and are part of a diverse collection of lipids called isoprenoids. They also fit into the terpene classification.
CH2 CCH3
CH CH2 CH2 CCH3
CH2CH2 O PO
O PO
OOOisoprene unit isopentenyl-
pyrophosphate
18-25
Steroids-2Steroid lipids are based on the ring system
shown below. The next slide shows some examples of steroid sex hormones and of cholesterol, a lipid very important in human physiology.
12
3
456
7
8
910
111213
14 15
16
17
A B
C D
18-26
Steroid Examples
CH CH2 CH2CH2CH(CH3)2
OH
H
CH3 H
CH3
H H
H
CH3
Cholesterol
O
CH3
CH3
OH
testosterone
O
CH3
CH3
C
CH3
O
progesterone
18-27
Wax Esters
Waxes are typically esters of fatty acids and fatty alcohols. They protect the skin of plants and fur of animal etc.
Examples of waxes include carnuba, from the leaves of the Brasilian wax palm, and beeswax.
CH3 CH2 C
O
O CH2 CH324 29
18-28
18.5 Complex Lipids
LipoproteinsThe term is most often used for
molecular complexes found in blood plasma of humans.
Contain: neutral lipid core of cholesterol esters and/or TAGs surrounded by a layer of phospholopid, cholesterol, and protein.
Classes: chylomycrons, VLDL, LDL, HDL
18-29
Lipoproteins-2Chylomycrons: very large and very low
density; transport intestineadipose
VLDL: made in liver; transport lipids to tissues; depleted one to LDLs.
LDL: carry cholesterol to tissues
HDL: made in liver; scavenge excess cholesterol esters; “good cholesterol”
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AtherosclerosisAtheromas (plaque) impede blood flow.
Plaque: smooth muscle cells, macrophages, cell debris
Macrophages fill with LDLs
Coronary artery disease a very common consequence. High plasma concentrations of LDLs correlate with risk.
18-31
Membrane Receptors
The LDL receptor was discovered during an investigation of familial hypercholesterolemia.
When a cell needs cholesterol, it synthesizes the receptor which migrates to a coated region of the membrane. The “captured” cholesterol is absorbed by endocytosis. Failure to make the receptor is the most common problem encountered.
18-32
18.6 MembranesEach type of cell has a unique
membrane composition with varying percentages of lipids, proteins, and some carbohydrates.
The currently accepted model of the membrane is the fluid mosaic model of a lipid bilayer.
Some examples follow on the next slide.
18-33
Composition of Some Membranes
Protein % Lipid % Carb. %
Human
erythrocyte
49 43 8
Mouse liver 46 54 2-4
Mitochon-
drial (inner)
76 24 1-2
Spinach
lamellar
70 30 6
G Guidotti, Ann Rev Biochem, 41:731, 1972
18-34
Membrane Lipids1. Fluidity
Lateral movement of phospholipids is rapid. Flip-flop, from one side to the other is rare.
Increasing percentage of unsaturated fats leads to more fluidity.
See next slide.
18-35
A fluid membrane model
18-36
Membrane Lipids-22. Selective permeability
The hydrophobic nature of the membrane makes it impenetrable to the transport of ionic and polar substances.
Membrane proteins regulate passage of ionic and polar substances by binding to the polar compound or by providing a channel.
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Membrane Lipids-33. Self-sealing capacity
A break in the membrane immediately and spontaneously seals.
4. Asymmetry
Bulkier molecules occur more often in the inner side of the membrane.
18-38
Membrane ProteinsMost membranes require proteins to carry out
their functions. Integral proteins are embedded in and/or
extend through the membrane.Peripheral proteins are bound to membranes
primarily through interactions with integral proteins.
18-39
Membrane TransportThe cell membranes is responsible for the
controlled passage of molecules and ions into and out of cells and organelles.
Binding of hormones and other biomolecules.
With passive transport, there is net movement of solute to a region of lower concentration (diffusion)
With facilitated diffusion, a membrane protein (a permease) assists in diffusion. The process still requires no energy and is passive.
18-40
Membrane Transport-2
Passive transport (no direct energy input)
Simple diffusion-molecules move through a membrane down a concentration gradient (toward lower concentration).
Facilitated diffusion-molecules move through protein channels in membrane.
18-41
OsmosisOsmosis is the net flow of water through
a semipermeable membrane (ie. Cell wall) from a region of low solute concentration to a region of high solute concentration.
Osmotic pressure is that which must be applied to prevent flow of water across the membrane.
18-42
Osmosis, cont.If a cell has a higher osmotic
concentration than the surrounding fluid, it’s fluid is said to be hypertonic. Water flows into the cell and it may burst or hemolyze.
If a cell has a lower osmotic concen-tration than the surrounding fluid, it’s fluid is said to be hypotonic. Water flows out og the cell and it shrinks or crenates..
18-43
Membrane Transport-3
Facilitated diffusion
Chemically or voltage-regulated
e. g. acetyl choline binds to a receptor; Na+ rushes into the cell causing depolarization which in turn opens a voltage gated channel for Na+. Repolarizaton begins when a voltage-gated K+ channel opens and K+ leave the cell.
18-44
Membrane Transport-4
Facilitated diffusion (cont.)
A carrier protein binds to a molecule. The protein changes conformation and releases the molecule into the cell.
This process speeds diffusion but cannot cause a net increase in solute concentration over diffusion limits.
18-45
Membrane Transport-5
Active transport
Primary-energy provided by ATP
e. g. the Na+-K+ pump (Next slide)
Secondary-concentration gradients generated by primary active transport are used to move substances across membranes.
e. g. Na+ gradient (Na+-K+ pump) used to transport glucose in kidney tubules.
18-46
Sodium-Potassium Pump
Insert Fig 18.21
18-47
Membrane Transport-6
Cystic fibrous is a result of a missing or defective plasma membrane glycoprotein called cystic fibrosis transmembrane conductance regulator (CFTR) which functions as a chloride channel in epithelial cells.
In CF, chloride is retained in the cells, thick mucous forms due to osmotic uptake of water in the cells. Chronic pulmonary problems and infections result.
18-48
The End
Lipids