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752
CHAPTER
24 Carbohydratesin Living Organisms
PRACTICE
EXERCISE
24.7
Explain why liver glycogen,but not muscle glycogen,is a source of glucoseto other body tissues.
24.1I Metoholicregulotion
AIM: To describehow hormonesregulotemetobolismthrough
the useof secondmessengers.
Focus
Many metabolic processesare
subject to hormonal control.
One of the most fascinating aspects of metabolism is its regulation-how
cellular processesare turned on when they are needed and turned off when
they are not. So that you can clearly grasp the regulation of glucose metabolism, you will first need to know more about how hormones control cellular processesin general.
Examples
of hormonal
control
Since metabolic reactions are enzyme-catalyzed,you might reasonably
expect the control of cellular metabolism to involve the regulation of
enz),Tneactivity, and it often does. In complex organisms such as human
beings,many processesare controlled byhormones. In fact, over 30 effects
of a single hormone, insulin, are knor,rm.You have already seen that hormones control basal metabolism (th),noxine),permeability of cellular
membranes(vasopressin),
and the activity of ion pumps (aldosterone).The
prostaglandins also exhibit hormone-like effects. The study of prostaglandins is complicated, though, by the fact that they seem to have opposite effectson different kinds of tissue cells,whereashormones influence all
their target cells in the same way.
NH,
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Second messengers
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Hormones are powerful regulatorsof processesthat occur inside cells,but
few hormones are ever found inside the cells they act on. The discoverythat
H-C
hormones that reach target cells bind to specificprotein receptorson the
outer surface of the cell membrane was an important contribution to the
o-cH2
study of hormones and cells. This discovery did not, however, explain how
hormones
influence processesinside cells.Scientistshad few leads to the
-O-Pr
H \13' ,
solution of this mysteryuntil Earl Sutherland and his colleaguesdiscofred
cyclicAMP (cAMP) in 1957 (Fig.2a.T. Their work, and the work ofthose
who followed them, has sho'ornthat formation of a hormone-receptorcomplex on the exterior of a cell membrane activates an enzyme, adenylate
Figure24.7
cycl.ase,
that is attached to the interior of the cell membrane (Fig. 2 .B).
Cyclic
adenosine
monophosphate
Adenylate
cyclase catalyzes the conversion of AIP to cAMP In most
(cAMP).Notethat in cAMPa cyclic
instances,
cAMP
then binds to the allosteric sites of a group of enzymes
phosphodiester
linkageisformed
protein
called
kinases.In
other words, cAMP is a positive modulator (see
betweenthe hydrorylgroupson
protein
19.10)
Sec.
of
kinases.
Activated protein kinases catalyzethe transthe 3' and5' positions
of the
phosphoryl
fer
groups
of
from
AIP to various proteins. These proteins are
ribosering.
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24.1I Metabolic Regulation
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Stimulus
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Hormone
(first messenger)
Hormone-receptor
complex
Figure24.8
Manyhormonesexerttheir
influenceon cellsby stimulating
the productionof cAMP,
the
secondmessenger.
mainly en4lmes that catalyze important cellular processes.Phosphorylation activates many of these en4rrnes, but it deactivates some; ultimately,
the presence of cAMP starts some cellular processesand stops others.
CyclicAMP a-lsomay play roles other than that of activating protein kinases.
In at least one instance, cAMP activates an en4rrne by releasing it from an
en4rme-inhibitor complex (Fig. 24.9).
Hormone action is often compared with a messengerservice in which
the hormone is the first messenger, deliuering a regul.atorynxessageto the
cell. Cyclic AMP is ofren the second.messenger, taking the messageto its
final destination: the enzymeswithin the cell. There are other second messengersbesides cAMP For example, scientists have found that the action
of some hormones is impaired in the absenceof calcium ions. They see
this effect at both low and high levels of cAMP in the cellular-cytoplasm.
-/
Inhibitor
Figure24.9
CyclicAMPactivates
some
enrymesby releasing
themfrom
inactivecomplexes.
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754
24 Carbohydrates
in LivingOrganisms
CHAPTER
This indicates that calcium ions rather than cAMP are the second messengers.Sometimescalcium ions and cAMP work together to causea certain effect on cellular metabolism. In addition to cAMP and calcium ions,
two very simple molecules have been found to serve as second messengers in many important physiologic processes.These molecules are discussed in A Closer Look Nitric Oxide and Carbon Monoxide as Second
Messengers.
Ni.tric Oxide and Carbon Monoxide
as SecondMessengers
In a world of complex biological molecules sueh as
cyclic AMB simple nitric oxide (NO) seems an
unlikely candidate for an important role in the
body. Its simplicity aside, nitric oxide (NO) is one
of the most important messengersin the body. A
specific enzyme, nitric oxide synthase,makes NO
from nitrogen in the amino acid arginine. Nitric
oxide is a gas under,atmospheric conditions. In
the body it lasts only 6 to I0 secondsbefore it is
oxidized by oxygen and water to nitrite ions
(NOz-) and nitrate ions (NOs-). Despiteits fleeting existence, NO is responsible for a host of
effects in the body. The molecule is toxic to many
kinds of cells,but certain white blood cells called
macrophagesare resistant to its toxicity. Macrophages contain NO and use it to kill tumor cells,
fungi, and bacteria- NO also relaxes muscles of
blood vessels,which permits the vesselsto expand
and reduce blood. pressure. Many patients who
suffer from angina pectoralis,chest pain that is
causedby spasmsof the arteries of the heart, are
treated with nitroglycerin.The relaxation of these
arteries relieves the symptoms of 4ngina. Nitroglycerinis degradedto NO in the body,the spasms
stop, and angina is relieved.NO simultaneously
behavesrnuch like a neurotransmitter in the brain
and other parts of the body.Learningand memory
are thought to involve the passageof neurotransmitter molecules between the nerve cells of the
brain (neurons).NO may enableus to learn and to
rememberwhat we have learned.
Perhapseven more surprising than NO as a
messengerin the bodyis the recent implication of
r:.,
carbon monoxide (CO). Most of usknowthat car'
bon monoxide is a toxic component of automobile
exhaust and other incomplete combustion of
hydrocarbons (Case in Point: Carbon monoxide
poisoning, page 316). Scientistshave found that
our bodies naturally make a small amount of carbon monoxide by the oxidation of heme, the'oxy-,
gen-carryingpart of the hemoglobin molecule in
red blood cells.An en4/rne called hdme oxygenase
catalyzesthe formation of carbon monoxide fiom
heme. The details of the action of carbon monoxide are sketchy at present, but it appears that this
tiny molecule is the main regulator of the arnount
of the secondmessengercGMP (seeSec.24.12)in
at least some brain ceils.
Macrophages
are resistantto the toxicityof nitricoxide
(No).