Chapter 24 Lipids. Lipids Lipids: Lipids: a class of naturally occurring organic compounds which...
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Transcript of Chapter 24 Lipids. Lipids Lipids: Lipids: a class of naturally occurring organic compounds which...
Chapter 24
LipidsLipids
Lipids
Lipids:Lipids: a class of naturally occurring organic compounds which are:– insoluble in water, but soluble in organic
solvents
Lipids are generally put into three classes– Storage Lipids– Structural Lipids– Lipids as Signals, Cofactors, and Pigments
Lipids
Storage Lipids (80% of the mass of a fat cell)– Fatty acids
• Long chain alkane or alkene with carboxylic acid at one end.
– Triacylglycerols• Glycerol triester of three fatty acids
– Waxes• Fatty acid ester with long chain alcohol
Lipids
Structural Lipids (5% to 10% of dry mass of most cells)– Phosphoacylglycerols (glycerophospholipids)– Galactolipids (glycolipids)– Sulfolipids– Sphingolipids– Cholesterol (and Bile acids)
Lipids
Signals, Cofactors, and Pigments– Steroid hormones – Lipid-soluble vitamins– Eicosanoids (not transported in the blood)
• Prostaglandins
• Thromboxanes
• Leukotrienes
Triglyceride
Triglyceride:Triglyceride: 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
Fatty Acids Fatty acid:Fatty acid: an unbranched-chain carboxylic acid
derived from hydrolysis of animal fats, vegetable oils, or membrane phospholipids– nearly all have an even number of carbon atoms, most
between 12 and 20, in an unbranched chain– the three most abundant are palmitic acid (16:0), stearic
acid (18:0), and oleic acid (18:1)– in most unsaturated fatty acids, the cis isomer
predominates; the trans isomer is rare– unsaturated fatty acids have lower melting points than
their saturated counterparts; the greater the degree of unsaturation, the lower the melting point
Fatty Acids COOHCOOH
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
Triglycerides
Physical properties depend on the fatty acid components– melting point increases as the number of carbons in the
hydrocarbon chains increases and as the number of double bonds decreases
– triglycerides rich in unsaturated fatty acids are generally liquid at room temperature and are called oilsoils
– triglycerides rich in saturated fatty acids are generally semisolids or solids at room temperature and are called fatsfats
Triglycerides The lower melting points of triglycerides rich in
unsaturated fatty acids are related to differences in their three-dimensional shape– hydrocarbon chains of saturated fatty acids can lie
parallel with strong London dispersion forces between their chains; they pack into well-ordered, compact crystalline forms and melt above room temperature
– because of the cis configuration of the double bonds in unsaturated fatty acids, their hydrocarbon chains have a less ordered structure and London dispersion forces between them are weaker; these triglycerides have melting points below room temperature
Hydrogenation
Hardening: reduction of some or all of the carbon-carbon double bonds of an unsaturated triglyceride using H2/catalyst– in practice, the degree of hardening is carefully
controlled to produce fats of a desired consistency
– the resulting fats are sold for kitchen use (Crisco, Spry, Dexo, and others)
– margarine and other butter substitutes are produced by partial hydrogenation of polyunsaturated oils derived from corn, cottonseed, peanut, and soybean oils
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 when used in water containing Ca(II), Mg(II), and Fe(III) 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
Complex LipidsComplex 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
Glycerol Sphingosine – amino alcohol
Membranes Complex lipids form the membranes around
cells and small structures within cells In aqueous solution, complex lipids
spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers– polar head groups are in contact with the aqueous
environment– nonpolar tails are buried within the bilayer– the major force driving the formation of lipid
bilayers is hydrophobic interaction– the arrangement of hydrocarbon tails in the interior
can be rigid (if rich in saturated fatty acids) or fluid (if rich in unsaturated fatty acids)
Fluid Mosaic Model
Glycerophospholipids GlycerophospholipidsGlycerophospholipids are the second most
abundant group of naturally occurring lipids– they are also called phosphoglycerides– found almost exclusively in plant and animal
membranes, which typically consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins
– the most abundant phosphoacylglycerols are derived from phosphatidic acid, a molecule in which glycerol is esterified with two molecules of fatty acid and one of phosphoric acid
– the three most abundant fatty acids in phosphatidic acids are palmitic (16:0), stearic (18:0), and oleic (18:1)
Glycerophospholipids
A phosphatidic acid
– the fatty acid on carbon 2 is always unsaturated
– further esterification with a low-molecular-weight alcohol gives 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
More often phosphatidyl____________
Glycerophospholipids
– a lecithin (phosphotidylcholine)a lecithin (phosphotidylcholine)
CH2
CH
CH2
O
O
O
O
O P OCH2CH2N(CH3)3
O
O-
+
palmitic acid
linolenic acid
glycerol
choline
Sphingolipids Found in the coatings of nerve axons
(myelin)– contain the long-chain aminoalcohol,
sphingosine,
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:: a complex lipid that contains a
carbohydrate– the carbohydrate is either glucose or galactose– the cerebrosides are ceramide mono- or
oligosaccharides
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 this tetracyclic ring structure
A B
C D
Cholesterol Cholesterol is the most abundant steroid in
the human body– in plasma membranes in all animal cells– precursor of all steroid hormones and bile acids
HO
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 Schematic of a low-density lipoprotein
Cholesterol Transport
– transport of cholesterol from the liver starts with VLDL
– VLDL is carried in the serum
– as fat is removed, its density increases and it becomes LDL; LDL stays in the plasma for about 2.5 days
– LDL carries cholesterol to cells, where specific LDL receptors bind it
– after binding, LDL is taken into cells where enzymes liberate free cholesterol and cholesteryl esters
Cholesterol Transport
– high-density lipoproteins (HDL) transport cholesterol from peripheral tissues to the liver and also transfer cholesterol to LDL
– while in the serum, free cholesterol in HDL is converted to cholesteryl esters
– in the liver, HDL binds to the liver cell surface and transfers its cholesteryl esters to the cell
– these esters are used for the synthesis of steroid hormones and bile acids
– after LDL has delivered its cholesteryl esters to liver cells, it reenters circulation
Levels of LDL and HDL– most of the cholesterol is carried by LDL– normal plasma levels are 175 mg/100 mL– if there are sufficient LDL receptors on the surface of
cells, LDL is removed from circulation and its concentration drops
– the number of LDL receptors is controlled by a feedback mechanism
– when the concentration of cholesterol inside cells is high, the synthesis of LDL receptors is suppressed
– in the disease called hypercholesterolemia, there are not enough LDL receptors and plasma levels of cholesterol may be as high as 680 mg/100 mL
Levels of LDL and HDL– these high levels of cholesterol can cause premature
atherosclerosis and heart attacks– in general, high LDL means high cholesterol content in
the plasma because LDL cannot get into cells– therefore, high LDL together with low HDL is a
symptom of faulty cholesterol transport and a warning of possible atherosclerosis
– the serum cholesterol level controls cholesterol synthesis in the liver
– when serum cholesterol is high, its synthesis in the liver is low, and vice versa
– the commonly used statin drugs inhibit the synthesis of cholesterol by blocking HMG-CoA reductase
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– decrease inflammation– involved in the reaction to stress
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
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 not stored in tissues as
such, but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers– one such polyunsaturated fatty acid is
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
The 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 resident cells, for example, smooth muscle cells
– this 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 Leukotrienes are also synthesized from
arachidonic acid– they occur mainly in leukocytes– they produce muscle contractions, especially in
the lungs … can cause asthma-like attacks– they are 100 times more potent than histamine– anti-asthma drugs inhibit leukotrienes synthesis
OH OHCOOH
Leukotriene B4
1512
20
End End Chapter 20Chapter 20
Lipids