Lipids

Lipids: A family of substances classified together on the basis of common solubility properties.
 Insoluble in water, but soluble in organic solvents including diethyl ether,
dichloromethane, and acetone.
The roles of lipids in human biochemistry include:
 Energy storage within cells
 Components of membranes in cells
 Chemical messengers
Lipids are classified into four groups based on their structures:
 Simple lipids (fats, oils, and waxes).
 Complex lipids.
 Steroids.
 Prostaglandins, thromboxanes, and leukotrienes.

Fatty Acids
The fatty acid components of triglycerides have certain
things in common:
1. Practically all are unbranched carboxylic acids.
2. They range in size from about 12 to 20 carbons.
3. They contain an even number of carbon atoms.
4. Apart from the –COOR ester groups, triglycerides have no functional groups, except that
some have one or more carbon–carbon double bonds in the fatty acid hydrocarbon chains.
5. In most fatty acids that have carbon–carbon double bonds, the cis isomers predominate.
Triglycerides
Triglyceride: A triester of glycerol with three fatty acids.
 In most triglycerides, two or three different fatty acid components are
present.
 The hydrophobic character of triglycerides is caused by the long
nonpolar hydrocarbon chains of the fatty acid components.
 The ester groups, although polar, are buried within a nonpolar
environment, which makes triglycerides insoluble in water.
  In triglycerides, all three hydroxyl
groups of glycerol are esterified with
fatty acids.

The physical properties of triglycerides depend

on the fatty acid components.
 Melting points of fatty acids 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 oils
 Triglycerides rich in saturated fatty acids
are generally semisolids or solids at room
temperature and are called fats.

Hydrogenation: The reduction of some or all of the carbon-carbon double bonds of an

unsaturated triglyceride using H2/transition metal catalyst, which converts a liquid triglyceride to
a semisolid.
 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 and others).
 Margarine and other butter substitutes are produced by partial
hydrogenation of polyunsaturated oils derived from corn, cottonseed,
peanut, and soybean oils.
 The hydrogenation process is the source of trans fatty acids (see Chemical Connections
17A).
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.

Figure 20.2 Schematic diagram of simple and complex lipids.

Biological Membranes
Complex lipids form the membranes around cells and around small structures within cells.
In aqueous solution, complex lipids spontaneously form into a lipid bilayer, with a tail-to-tail
arrangement of lipid monolayers.
 Polar (hydrophilic) head groups are in contact with the aqueous environment.
 Nonpolar (hydrophobic) tails are buried within the bilayer and shielded from the aqueous
environment.
 The major driving force for the formation of


lipid bilayers is hydrophobic interaction.
 Unsaturated fatty acids prevent tight packing of the hydrophobic chains; the resulting
liquid-like membrane allows for molecular transport across it.
 Fluid Mosaic Model

Glycerophospholipids
Glycerophospholipids, also called phosphoglycerides, are membrane components of cells
throughout the body.
 The most abundant glycerophospholipids are derived from phosphatidic acid, a molecule
in which glycerol is esterified with two molecules of fatty acid and one of phosphoric
acid.
  The fatty acid on carbon 2 of glycerol is usually unsaturated.

The structure of glycerophospholipids is very similar to that of fats.

 The alcohol is glycerol.
 Two of the three hydroxyl groups are esterified with fatty acids. The third hydroxyl group
is esterified with phosphoric acid, which is also esterified with another alcohol.

If the other alcohol is choline, the glycerophospholipid is called a phosphatidylcholine (common

name lecithin).

Cephalins: Another group of glycerophospholipids in which the additional phosphate ester is

provided by either ethanolamine
or serine.
 Sphingolipids
 Contain the long-chain aminoalcohol, sphingosine, from which this class of compounds
in named.
 The sphingolipid myelin is found in the coatings of nerve axons.

Glycolipids
Glycolipid: a complex lipid that contains carbohydrates and ceramides.
 The carbohydrate is either glucose or galactose.
 The cerebrosides are ceramide mono- or oligosaccharides.
 The following is a glucocerebroside.

Steroids
Steroids: A group of plant and animal lipids that contains
this tetracyclic ring structure.
 Cholesterol
Cholesterol is the most abundant steroid in the human body, and also the most important.
 It is a component in plasma membranes in all animal cells.
 It is the precursor of all steroid hormones and bile acids.

Lipoproteins
Lipoproteins: Carriers of cholesterol.
 Most lipoproteins contain a core of hydrophobic lipid molecules surrounded by a shell of
hydrophilic molecules such as proteins and phospholipids. There are four kinds of
lipoproteins.
 High-density lipoprotein (HDL) (“good cholesterol”), which consists of about 33%
protein and 30% cholesterol.
 Low-density lipoprotein (LDL) (“bad cholesterol”). which contains about 25% protein
and 50% cholesterol.
 Very-low density lipoprotein (VLDL), which carries triglycerides (fats) synthesized by
the liver.
 Chylomicrons, which carry dietary lipids synthesized in the intestines.
Lipoprotein Composition

Low-Density Lipoprotein
 Cholesterol Transport
 Transport of cholesterol from the liver starts out as a large VLDL particle.
 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 from
cholesteryl esters.

 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 HDL 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 in blood plasma 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 famelial hypercholesterolemia, there are not enough LDL receptors
and plasma levels of cholesterol may rise as high as 680 mg/100 mL.
 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.
 Adrenocorticoid Hormones
 Synthesized in the adrenal cortex.
 Decrease inflammation.
 Involved in the reaction to stress.
 Mineralocorticoids regulate ion concentrations
 Glucocorticoids control carbohydrate metabolism
 Aldosterone, a mineralocorticoid, controls tissue
swelling.

Steroid Hormones
 Male sex hormones
 Synthesized in the testes from cholesterol.
 Responsible for the development of male secondary sex characteristics.
Figure 20.7 Cholesterol is first converted to progesterone and then to both sex hormones and
adrenocorticoid hormones.

Among the synthetic anabolic steroids are:

Bile Salts
Bile salts are 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.
Female sex hormones
 Synthesized in the ovaries from progesterone.
 Responsible for the development of female secondary sex characteristics and control of
the menstrual cycle.

Progesterone-like analogs are used in oral contraceptives:

 Prostaglandins
Prostaglandins: a family of compounds synthesized in the body from arachidonic acid by a ring
closure between carbons 8 and 12.

The enzyme that catalyzes prostaglandin formation is cyclooxygenase (COX for short).
 COX Enzymes

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.

Leukotrienes
Leukotrienes are also synthesized from arachidonic acid.
 They occur mainly in leukocytes.
 They produce muscle contractions, especially in the lungs and thereby can cause asthma-
like attacks. They are 100x more potent than histamine.
 Several recently-developed anti-asthma drugs inhibit the synthesis of leukotrienes