lipids bettelheim, brown, campbell and farrell chapter 21
TRANSCRIPT
Lipids
Bettelheim, Brown, Campbell and Farrell
Chapter 21
Lipids
• Lipids:Lipids: a heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties– insoluble in water, but soluble in organic
solvents including diethyl ether, dichloromethane, and acetone
Functional Classification of Lipids
• Storage of energy in animals
• Membrane components– Lipid bilayer
• Messengers – Primary: Hormones– Secondary: mediate hormonal response
• prostaglandins, thromboxanes, etc.
Lipids
• Lipids include– fatty acids, triacylglycerols, sphingolipids,
phosphoacylglycerols, and glycolipids – lipid-soluble vitamins– prostaglandins, leukotrienes, and
thromboxanes– cholesterol, steroid hormones, and bile acids
Structural Classification of Lipids
• Simple Lipids – Fatty acids, waxes
• Complex Lipids– Multiple components
• Steroids
• Prostaglandins, Thromboxanes and Leukotrienes
Fatty Acids• Fatty acid:Fatty acid: an unbranched-chain carboxylic acid derived
from hydrolysis of animal fats, vegetable oils, or membrane phospholipids– Usually unbranched chain with 10-20 carbons– EVEN number of carbons– May be saturated or unsaturated (C=C)– Unsaturated generally have cis double bonds– Unsaturated fatty acids have lower melting points than their
saturated fatty acids– Most abundant are palmitic acid (16:0), stearic acid (18:0),
and oleic acid (18:1)
Fatty Acid Notation
• (18:0) = 18 C and no double bonds
• (18:1) = 18 C and one double bond
• (18:3) = 18 C and three double bonds
Table 20.1, p.496
Fatty AcidsCOOH
COOH
COOH
Unsaturated Fatty Acids
Saturated Fatty Acids
20:418:3
18:218:116:1
20:018:016:014:012:0
Carbon Atoms/Double Bonds*
MeltingPoint(°C)
Common Name
-49-11
-5161
7770635844
Arachidonic acidLinolenic acidLinoleic acidOleic acidPalmitoleic acid
Arachidic acidStearic acidPalmitic acidMyristic acid
Lauric acid
Waxes
• High molecular-weight esters
OCH2
CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH3
O CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH3
46 C total for triacontyl palmitate
Fats and Oils
• Contain glycerol and fatty acids
• Glycerol is triol
• Combined with ester
bonds
Triglycerides
• Triglyceride (triacylglyceride):Triglyceride (triacylglyceride): an ester of glycerol with three fatty acids
O
CH2OCR
CH2OCR''
R'COCH
OO
1. NaOH, H2O
2. HCl, H2O CH2OH
CH2OH
HOCH
RCOOH
R'COOH
R''COOH
A triglyceride 1,2,3-Propanetriol(Glycerol, glycerin)
+
Fatty acids
Example of triglyceride
Triglycerides
• Triglyceride (triacylglyceride):Triglyceride (triacylglyceride): an ester of glycerol with three fatty acids
O
CH2OCR
CH2OCR''
R'COCH
OO
1. NaOH, H2O
2. HCl, H2O CH2OH
CH2OH
HOCH
RCOOH
R'COOH
R''COOH
A triglyceride 1,2,3-Propanetriol(Glycerol, glycerin)
+
Fatty acids
Triglycerides
• Physical properties depend on the fatty acid components– More carbons: higher melting point – More saturated (fewer C=C): higher melting point– Oils:Oils:
• More unsaturated fatty acids • Liquid at room temperature
– Fats:Fats: • Primarily saturated fatty acids • Semisolids or solids at room temperature
Triglycerides
• Melting points related to 3-D shape of triglyceride– Saturated fatty acids can pack closely together
• More London dispersion forces between chains• Higher melting points (above room temperature)
– Unsaturated fatty acids have cis double bonds • Bend in chain prevents close packing• Fewer London dispersion forces between them• Lower melting points (below room temperature)
Packing of Saturated vs Unsaturated Fatty Acids
Hydrogenation
• Can convert liquid oil to solid fat by adding H2 to double bonds by using H2/catalyst
– Can control hardening to produce fats of a desired consistency
– Examples: Crisco, Spry, Dexo, etc.– Margarine produced by partial hydrogenation of
polyunsaturated oils derived from corn, cottonseed, peanut, and soybean oils
Hydrogenation of triglyceride
HC
H2C
H2C C (CH2)12 CH3O
O
O
O
C (CH2)6 CH2
CH CH
CH2 (CH2)6 CH3
O
C (CH2)6 CH2
CH CH
CH2 (CH2)6 CH3
O
+ H2
catalyst
HC
H2C
H2C C (CH2)12 CH3O
O
O
O
C (CH2)6 CH2
CH2 CH2
CH2 (CH2)6 CH3
O
C (CH2)6 CH2
CH2 CH2
CH2 (CH2)6 CH3
O
Iodine or Bromine Test for Unsaturation
• Add Br2 (or I2) to C=C.
• The more Br2 or I2 you add, the greater the number of double bonds in the fat or oil
• Iodine number is a measure of unsaturation.
Soaps
• Natural soaps are prepared by boiling lard or other animal fat with NaOH, in a reaction called saponificationsaponification (Latin, sapo, soap)
Sodium soaps
1,2,3-Propanetriol(Glycerol; Glycerin)
A triglyceride(a triester of glycerol)
+
saponification+CH
CH2OCR
CH2OCR
CHOH
CH2OH
CH2OH
RCO 3NaOH
3RCO- Na
+
O
O
O
O
Soaps
• Soaps clean by acting as emulsifying agents– their long hydrophobic hydrocarbon chains cluster
so as to minimize their contact with water– their polar hydrophilic carboxylate groups remain in
contact with the surrounding water molecules– driven by these two forces, soap molecules
spontaneously cluster into micelles
Soaps
– Soaps form water-insoluble salts (scum) when used in water containing Ca2+, Mg2+, and Fe3+ ions (hard waterhard water)
2CH3(CH2)14COO- Na
+Ca2+
[CH3(CH2)14COO-]2Ca
2+2Na++
+
A sodium soap(soluble in water as micelles)
Calcium salt of a fatty acid(insoluble in water)
Complex Lipids
• Phospholipids– contain an alcohol, two fatty acids, and a
phosphate ester– in glycerophospholipids, the alcohol is
glycerol– in sphingolipids, the alcohol is sphingosine
• Glycolipids– complex lipids that contain a carbohydrate
Fig 20.1, p.501
Complex Lipids
Complex Lipids
Phospholipids
GlycolipidsGlycerophospholipids Sphingolipids
G l y c e r o l
S p h i n g o s i n e S p h i n g o s i n e
Fatty acid
Fatty acid
PO4-alcohol
Fatty acid
Fatty acid
Glucose orGalactose
PO4-Choline
Membranes• Complex lipids form the membranes around cells
and small structures within cells• In aqueous solution, complex lipids form into a
lipid bilayer, with a back-to-back arrangement of lipid monolayers– polar head groups are hydrophilic and point to aqueous
environment– nonpolar tails are hydrophobic and are inside the
bilayer– hydrophobic interactions drive bilayer formation– Rigidity of membrane depends on whether fatty acid
tails are saturated or unsaturated
Membrane bilayer
• Hydrophilic head outside
• Hydrophobic tails inside
Membrane Rigidity
• Depends on nature of fatty acid tails– Saturated fatty acids = more rigid– Unsaturated fatty acids = less rigid
– Reindeer legs• Near foot membranes have different fatty acid
composition than in other parts of animal
Fig 20.1, p.501
Membrane bilayer
• Hydrophilic head outside
• Hydrophobic tails inside
Fluid Mosaic Model
Transport across membrane
• Passive transport– Gap junctions—6 proteins make a central pore– Small molecules pass through pores
• Ions, sugars, amino acids, nucleotides• Large molecules can’t pass through
– Pore can be open or twisted shut
• Facilitated transport– Interaction between transporter and transported molecule
• Active transport—– Ions transported against concentration gradient– Energy expended to change shape of protein and transport
ion across membrane
Transport across membranes
• Active transport—– Ions transported against concentration
gradient– Energy expended to change shape of protein
and transport ion across membrane– Polar compounds transported via specific
transmembrane channels.
Fig 20.1, p.501
Complex lipids found in membranesSimple lipids
Glycerophospholipids• GlycerophospholipidsGlycerophospholipids (phosphoglycerides) are
the second most abundant group of naturally occurring lipids– found in plant and animal membranes, which
consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins
– Major phosphoacylglycerols are derived from phosphatidic acid
• glycerol + 2 fatty acids + phosphate
– Most abundant fatty acids in phosphatidic acids are palmitic (16:0), stearic (18:0), and oleic (18:1)
Glycerophospholipids
• A phosphatidic acid
– Fatty acid attached to C-2 is always unsaturated– Can also add small alcohol to the phosphate to
make a glycerophospholipid
CH2
CH
CH2-O-P-O-
O
O
O
Oglycerol
palmitic acid
oleic acid
O
O-
Glycerophospholipids
HOHO
OHOH
OH
OH
NH3+
HOCH2CHCOO-
HOCH2CH2N(CH3)3
HOCH2CH2NH2
inositol phosphatidylinositol
Name and FormulaName of Glycerophospholipid
ethanolamine
+choline lecithin
cephalin
serine cephalin
Glycerophospholipids
– a lecithina lecithin
CH2
CH
CH2
O
O
O
O
O P OCH2CH2N(CH3)3
O
O-
+
palmitic acid
linolenic acid
glycerol
choline
Glycerophospholipids
• Phosphatic acid– Glycerol, 2 fatty acids, phosphate
• Lecithins– Glycerol, 2 fatty acids, phosphate, choline
• Cephalins– Glycerol, 2 fatty acids, phosphate,
ethanolamine or serine
Sphingolipids
• Found in the myelin sheath of nerve axons– Sphingomyelin deterioration found in MS
• Contain sphingosine, a long-chain aminoalcohol
OH
(CH2)12CH3
HO
NH2
SphingosineOH
(CH2)12CH3
HO
NHCR
A ceramide(an N-acylsphingosine)
OPOCH2CH2N(CH3)3
(CH2)12CH3
HO
NHCR
A sphingomyelinO
O-+
O O
Glycolipids• GlycolipidGlycolipid:: complex lipid that contains a sugar
– Sugar is glucose or galactose– Cerebrosides found in brain and nerve synapses
O
(CH2)12CH3
HO
NHCR
O
H
HO
H
HO
H
HOH
H
OHO
a-glycosidic bond
a unit of -D-glucopyranose
a ceramide
Steroids
• SteroidsSteroids:: a group of plant and animal lipids that have a steroid ring structure
A B
C D
Cholesterol• Cholesterol is the most abundant steroid in
the human body, and also the most important– Component in animal plasma membranes – Precursor of all steroid hormones and bile acids
HO
Lipoproteins• Schematic of a low-density lipoprotein
Lipoproteins
• Cholesterol, along with fats, are transported by lipoproteins
Lipoprotein
Composition (% dry weight)
ProteinsCholesteroland esters
Phospho-lipids
Tri-glycerides
High-densitylipoprotein (HDL)
Low-densitylipoprotein (LDL)
Very-low densitylipoprotein (VLDL)
Chylomicrons
33 30 29 8
25 50 21 4
10 22 18 50
1-2 8 7 84
Lipoproteins
• Protein has a higher density than lipids do
• HDL (high density lipoprotein)– Have higher protein to lipid ratio
• LDL (low density lipoprotein)– have lower protein to lipid ratio
Cholesterol Transport—from liver to peripheral cells
– Transport from the liver starts with VLDL (55 nm)• Carried in plasma
– Density increases as fat is removed• VLDL becomes LDL (22 nm)• LDL stays in the plasma for about 2.5 days
– LDL carries cholesterol to cells, where specific LDL receptors (coated pits) bind it
– LDL is taken into cells where enzymes liberate free cholesterol and cholesteryl esters
Cholesterol Transport—from peripheral cells to liver
– HDL transport cholesterol from peripheral tissues to the liver and also transfer cholesterol to LDL
– Free cholesterol in HDL is converted to cholesteryl esters (while in serum)
– HDL binds to the liver cell surface and transfers its cholesteryl esters to the cell
– Cholesterol esters are used for the synthesis of steroid hormones and bile acids
– after HDL has delivered its cholesteryl esters to liver cells, it reenters circulation
• Cholesterol forms plaque deposits on inside of blood vessels (atherosclerosis)
• Narrows blood vessel diameter
• Lowers blood flow
• Can lead to heart attack, stroke, kidney disfunction or other problems
Levels of LDL and HDL
– Most cholesterol is carried by LDL– Normal plasma levels are 175 mg/100 mL– LDL is removed from circulation if there are
enough LDL receptors on cells– Number of LDL receptors controlled by feedback
mechanism• High cholesterol inside cell suppresses receptor
synthesis
– Hypercholesterolemia: not enough LDL receptors• High plasma cholesterol levels (up to 680 mg/100 mL)
Levels of LDL and HDL
– High LDL together with low HDL is a symptom of faulty cholesterol transport and a warning of possible atherosclerosis
– Serum cholesterol level controls cholesterol synthesis in the liver
• High serum cholesterol results in low synthesis of cholesterol in liver, and vice versa
• Statin drugs inhibit the synthesis of cholesterol
Steroid Hormones
• Androgens:Androgens: male sex hormones– synthesized in the testes– responsible for the development of male
secondary sex characteristics
AndrosteroneTestosteroneO
OH
H3C
H3C H3C
H3C
O
HO
Steroid Hormones
• Among the synthetic anabolic steroids are
O
H3C
H3C
MethandienoneO
CH3
H3CH3C
OHOH
CH3
MethenoloneO
H3C
H3C O
4-Androstene-3,17-dione
Steroid Hormones• Estrogens:Estrogens: female sex hormones
– synthesized in the ovaries– responsible for the development of female
secondary sex characteristics and control of the menstrual cycle
H3C
H3C
C=O
O
CH3
OH
HO
H3C
Progesterone Estradiol
Steroid Hormones
• Progesterone-like analogs are used in oral contraceptives
H3C
O
OHC CH
H3C
O
OHC CCH3
NH3C
CH3
"Nor" refers tothe absence of a methyl group here
Norethindrone
Mifepristone(RU486)
Steroid Hormones• Glucorticoid hormonesGlucorticoid hormones
– synthesized in the adrenal cortex– regulate metabolism of carbohydrates– involved in the reaction to stress– decrease inflammation
Aldosterone
C=O
CH2OH
O
H
H3C H
H
CHO
OH
Bile Salts
• Bile saltsBile salts, the oxidation products of cholesterol– synthesized in the liver, stored in the gallbladder,
and secreted into the intestine where they emulsify dietary fats and aid in their absorption and digestion
HO OH
HO NH
O
COO-
HO OH
HO NH
O
SO32-
Glycocholate(from glycine)
Taurocholate(from taurine)
Prostaglandins
• Prostaglandins:Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid
COOH2
3
4
5
67
89
2011
1213
1415
1617
1819
1
10
Prostaglandins
• Prostaglandins are synthesized in response to specific physiological triggers
• Made from membrane-bound 20-carbon polyunsaturated fatty acids such as arachidonic acid
COOH
Arachidonic acid1514
89
11 12
6 5
ProstaglandinsCOOH
2O2
OOH
COOHO
O
OH
COOH
O
HO
COOH
OH
HO
HO15
9 9
11 11
Arachidonic acid
PGF2PGE2
PGG2
Aspirin and other NSAIDs inhibit this enzyme
15
9
11
9
11
15
15
cyclooxygenase (COX)
COX Enzymes• COX enzyme occurs in two forms
• COX-1 catalyzes the normal physiological production of prostaglandins
• COX-2 is responsible for the production of prostaglandins in inflammation– when a tissue is injured or damaged, special
inflammatory cells invade the injured tissue and interact with tissue cells
– interaction activates COX-2 and prostaglandins are synthesized
Thromboxanes• Thromboxanes are also derived from
arachidonic acid– thromboxane A2 induces platelet aggregation and
vasoconstriction– aspirin and other NSAIDs inhibit the synthesis of
thromboxanes by inhibiting the COX enzyme
O
OOH
COOH
Thromboxane A2
189
11 201512
10
Leukotrienes• Synthesized from arachidonic acid
– occur mainly in leukocytes– produce muscle contractions, especially in the
lungs and thereby can cause asthma-like attacks– 100 times more potent than histamine – Many new anti-asthma drugs inhibit the synthesis
of leukotrienesOH OH
COOH
Leukotriene B4
1512
20