Download 17.10 Plant steroids l7.l I Prostoglondins ond leukotrienes

17.1I Prostaglandins
and Leukotrienes
545
sivevaginalbleeding.In the 1940sand early 1950s,DESwas routinely used
to prevent spontaneous abortions (miscarriages). This practice was
stopped when several studies showed that daughters born to women who
took DES have a higher-than-averageincidence of vaginal cancer after
I
reachingpuberty.
17.10Plant steroids
AIM: To stote the sourceond of least one function of digitoxin.
Focus
Digitalis is a mixture of plant
steroids used to treat heart
disease.
Many plants produce steroids also. Nobody knows, though, what function
many of these compounds have in plants. Many plant steroids are toxic to
humans. Nevertheless,one of the oldest drugs,in use since 1785,is in fact a
mixture of toxic steroids. The drug is digitalis, obtained from the common
foxglove plant. Digitalis is potentially deadly, but in very small doses it
improves the tone of heart muscles and is widely used to treat congestive
heart failure. Digitoxin is one of the major components of digitalis. Digitoxin has a steroid dng system, but it is unlike animal steroids in that the
steroid part of the molecule is attached to a carbohydrate part.
Digitoxin
l7.l I Prostoglondinsond leukotrienes
AIM: Torecognizeprostaglandinsand leukotrienesond stote
severolof their biologicol effects.
Prostaglandins and
leukotrienes infl uence many
bodv functions.
Prostaglandins are a classof fatty acid deriuatiuesthat haue a wide range of
physiologic actiuity. These substances have hormone-like effects. Unlike
hormones, however, they are not transported to their site of action in the
bloodstream but are qmthesized in the same environment in which they
act. Prostaglandinsare involved in the control of pain and fever, acid secretion into the stomach,relaxationand contraction of smooth muscle,blood
pressure, and the wake/sleep cycle. They also stimulate many inflammatory responses,particularly of the joints (rheumatoid arthritis), skin (psori-
Y
546
CHAPTER
l7 Lipids
asis),and eyes.It seemslikely that prostaglandins play a role in almost every
stageof reproduction.
Since their initial discovery in the 1930s,more than a dozen different
prostaglandins have been identified. Slight structural differences account
for their distinct biological effects. Prostaglandins are qmthesized in the
body by oxidation and cyclization of unsaturated continuous-chain fatty
acids containing 20 carbons.Arachidonic acid is one such acid.
o
lc-oH
CH:
20
Arachidonic acid
This acid is converted into a prostaglandin structure when the eighth and
twelfth carbons fuse to make a cyclopentane ring. Everyprostaglandin moleculecontains20 carbonsarrangedin the basicstructureof prostanoicacid.
o
C-oH
I
.tP.,
Prostanoicacid
Prostanoicacid is so named becauseprostaglandinswere first isolated
from human semen, and scientists thought that they were produced in the
prostate gland. It is now knor,trnthat they are present in minute amounts in
nearly all animal tissues and fluids.
ProstaglandinE2 demonstratesthe widespread effects of prostaglandins on a variety of body functions. ProstaglandinE2 does not itself cause
pain, but it enhancesthe intensity of the pain induced by other pain-producing chemicals in the body. This prostaglandin also induces the signs of
inflammation such as swelling, redness,and heat in the inflamed body part.
It also lowers arterial blood pressure and promotes blood clotting.
Prostaglandin E2and prostaglandin F2ohave been used extensivelyas drugs
in reproductive medicine, where they can be employed to induce labor and
terminate pregnancy.
COOH
ProstaglandinE2
CHs
Prostaglandin F2"
Summary lt47
Aspirin blocks the synthesis of prostaglandins that induce pain and
fever. It also has been reported that low dosesof aspirin reduce the danger
of heart attack and stroke by blocking the synthesis of prostaglandins that
promote blood clotting. Aspirin's inhibition of the formation of these
prostaglandins accounts for its effectivenessas an analgesic (pain killer),
antipyretic (fever killer), and anticlotting agent.
Leukotrienes are another classof hormone-like substancessynthesized
from arachidonic acid. Leukotriene Bn and leukotriene En are examples of
leukotrienes. Unlike the prostaglandins, the leukotrienes contain three carbon-carbon double bonds in a row in their molecular structures.
I
NHz
Leukotriene Ea
Certain leukotrienes constitute what is referred to as the slow-acting substances of anaphylactic shock. Anaphylactic shock is a drastic allergic
response of the body that can be fatal. Severeallergies to foods such as
shellfish or peanuts can tdgger anaphylactic shock in susceptible people.
The syrnptoms of anaphylactic shock include closing of the throat, blocking
the airways. Heart stoppage also can occur, Ieading to death. Leukotrienes
are also implicated in less severeallergic reactions, asthma, inflammations,
and heart attacks. Recent studies suggestthat dietary fish oils can reduce
levels of leukotrienes and reduce the risk of heart attack.
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Lipids are a broad class of naturally occurring, relatively water-insoluble molecules. Triglycerides-triesters of glycerol and fatty acids-are the most
abundant lipids in animal tissue.
The membranes of all cells are composed of
lipids. The major lipids of cell membranes are the
phospholipids, the glycolipids, and in animal cells,
cholesterol.Phospholipidshave a backbone of glycerol (phosphoglycerides)or of sphingosine (sphingomyelins). Cerebrosides,containing glucose or
galactose,with a backbone of sphingosineare com-
mon glycolipids.Phospholipid and glycolipid molecules have polar heads and hydrophobic tails. The
lipid bilayer is the fundamental structure of liposomes and the membranes of cells and organelles.
Its behavior is best described by a fluid mosaic
model. Proteins,which may be peripheral or integral, are associatedwith cell and organelle membranes. Membrane proteins are often glycoproteins.
Steroid molecules have no structural features in
common with other lipids. They are often classified
as lipids, however, because,like fatty acid esters,