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The two slow-moving

Molecules
and Cells animals pictured here are able to consume fast-moving prey b
ecause they
evolved
wayshave
to defeat the function of essential molecules and cellular structur
es inadder
puff
theirisprey.
one of
Thethe slowest moving of snakes. It feeds on fast-moving rats,
needs
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at will destroy
cellular
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key on
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which a rat depends for life. Like rattlesnakes and other
sits
adders,
and waits
the puff
foradder
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at its
in,victim,
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t attack
and
cells.critical
The snake
molecules
then immediately releases the rat and tracks the victim as
the rats molecularcellular
mechanisms
fall apart. Some of the injected compounds, for instance, strip the o
uterrats
the
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cells, whereas other compounds make tiny holes in the rats blood c
apillaries,internal
widespread
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hemorrhaging. When, finally, the molecularcellular damage is
so great
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The
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example
the offunction,
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the slow-moving
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onsnailfeeds
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t deceives
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theThe
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harpoons the fish with a hollow barbed tooth. The f
ish could
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justitself
a moments time to do so. The snail preempts such escape b
y injecting
the
fish through the tooth with compounds that almost instantly disrupt the func
of proteins that are essential for the function of the fishs nerve and muscle cel
tion
ls. the
way
In this
fishs most promising defense, its ability to swim rapidly away, is immedi
defeated. With the cells in its nervous system in disarray and its muscles paral
ately
yzed,actions
fish
The
istheingested
of venoms
by theandsedentary
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snail. us that all the higher functions of ani
depend on molecules and on the organization of molecules into cellular structure
mals
s and An animal as spectacular as a racehorse or a mind as great as that of Soc
cells.
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scientists,
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iscells
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ifecosystems
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32while,
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lipids
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ester
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Physiology
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athe
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33head,
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symbolizes
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34152535
Whereas
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Bass
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70
30
50
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Typical
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tails
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Figure
(CH2CH2NH2),
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fish
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average
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ais
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ain
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Molecules
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BOX
AND
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10.
phospholipid
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principal
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membranes.
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and
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because
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some
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and
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2.1.
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be
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10
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35in
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36string
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Although
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37
The
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2.5a).
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2012
38
can
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10
mitochondria.
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FIGURE
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left).
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accelerate
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45of
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compounds):
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46single
substrates
NAD.
kinetic
reaction
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Reversible
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equilibrium.
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Each
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FIGURE
isozyme,
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Figure
50
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Phosphorylation and dephosphorylation Molecules and Cells in Animal Physiology 5


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52famous
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SUMMARY
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54Biological
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15.
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55jellyfish
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56light
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change)the
seconds,
and
because
in
depends
probably,
some
use
skin
green,
pigments,
are
light-producing
luciferase
O2,
understood
which
(Vibrio
generally
importance
color
individual
approximation,
cell
granules
jellyfish
with
light
but
example
affects
those
in
pigment-containing
the
as
of
the
glow
is,
aenzyme
turn
is
straightforward
symbioses
in
imparts
which
In
aprocessto
of
because
on
aggregated
the
any
they
peroxide
proteins
and
agent),
their
animals
is
this
frogs,
yellow
28
the
clusters
of
it
reactions
complex
initiated
than
Box
the
colors.
Color
cell,
mechanismsstill
center
light-producing
is
the
GFP,
light
to
each
insight
microbial
afor
change
ofcytoskeleton)
green
decays,
on
the
pigments
rich
minutes,
is
color
effect
fluorescence
pathway
light
hides
and
an
fischeri)
dark
sor
are
light-producing
green
converts
that
generate
in
produce
2.2,
of
an
skin
sense,
ones
each
within
toward
their
intact
often
the
luciferin
ahaving
example,
ability
that
in
found
discovered
and
catalyzes
Aequorea
inactive
in
generation
only
is
flatfish,
may
or
change
the
fully
issome
luciferases,
which
most
depend
are
how
animals
quite
best
in
(Figure
intermediate
if
called
substrate,
depends
Thus,
the
of
ofcomplex
emissionis
catalyzes
particular
wavelengths
the
available
(or
rapid
containing
white
about
tightly
on
because
in
said
exists.
emitting
aby
have
each
cell
color
photoprotein
widespread
is
said
present.
establishedas
an
light.
absorb
aor
the
along
cells,
photocytes
cases,
their
endogenous
pigment
form
the
aggregating
understoodare
the
GFP.
afact
exposure
induces
scenario
Hawaiian
from
squid
different
other
process
of
is
flatfish
chromatophore
transferred
on
animal
the
at
chromatophores
tocolor
singlet
jellyfish
aform
in
green
color
cellsin
several
pigments
0.31.0
chromatophore
cell.
as
granules
periphery
inthat
2.24).
combination
color,
individuals
and
on
achieved
to
cells
emission
in
final
photoprotein.
symbiotic
must
most
of
together
being
ofthe
be
that
The
own
their
the
or
aanimal
geometries
Aequorea
however,
result
aluciferin
synthesize
today
outer
and
mechanism
this
and
luciferinluciferase
Marine
of
that
crayfish,
red
pigment
whole
the
generated
oxidized
compound,
photon
athat
can
reflect
wavelengths
of
change
When
West
use
GFP
luciferases
light.
are
bobtail
acquire
awater
of
but
radiate
are
step
on
there
electronically
conformational
photocytes.
their
the
matter,
lighten
function
types
micrometer
skin.
elucidated
isdisperses
thus
diet.
great
few
the
pigments,
may
pigment
presence
jellyfish,
(see
on
achieve
integument)
absorbs
looks
by
the
wavelengths
by
emits
from
travel
known
the
takes
at
as
Coast
found
Ca2+-activated.
animals
catalyzing
bacteria
subject
involved.
move
of(Figure
in
the
to
hours.
skin
granules
dispersing
be
molecular
oxidation.
are
an
photoprotein
However,
bacteria
when
of
cell
aWhen
skin.
long
generates
margin
by
Atheir
squid
specific
physiological
individuals
granules
out
alight
when
the
which
visible
Light
its
depending
green
change
on
present.
tiny
essentially
pathway
light
enormous
in
more
mechanisms
of
chromatophores
on
ofto
on
luciferin
the
many
are
ofthe
are
illuminated
(.m)
has
the
as
most
ocean
For
the
ahave
spot
green
production,
aof
the
particularly
acolor
light.
or
few

Molecules
BOX
SQUID
COORDINATION:
TFISCHERI
scolopes
relationship
bioluminescent
animal
in
mantle
is
Bacteria
center
squid,
downward
squid
starlight
symbiosis
antipredatory
light
intensity
down
termed
does
Each
its
recruits
which
that
Asymbiosisentails
specific
deep
the
impossible!
story,
symbionts
by
confocal
of
Soon
[lower].)
bacteria
epithelial
after
induce
to
(a)
Microtubules
as
Note
from
Pigment
aggregated
cell
along
Wallin
10
(b)
FIGURE
Dispersal
Aggregation
chromatophores
hethe
young
Hawaiian
nocturnally
Margaret
athe
its
those
use
J.
populate
fibrous
.m
2.2
environment
squid
symbionts
Microtubules
Aggregation
Photomicrograph
bi-lobed
through
not
predator
squid
its
this
crypts
after
that
the
but
AND
blends
is
it
Foster
they
bacteria
microtubules
houses
(body)
bacterial
Aemit
squid
counterillumination),
seawater
Bsee
of
to
1998.)
2.25
squid
granules
SYMBIOSIS
forms
in
so
The
emitted
cast
V.
develops
egg.
bacterial
very
Acquisition
microscopy.
specifically
cell
can
BIOLUMINESCENT
the
when
for
of
recruitmentthe
and
Both
immunocytochemistry
be
they
acquires
aBox
surfaces
are
white
at
bobtail
bioluminescent
that
McFall-Ngai.)
fischeri
within
For
the
Pigment
with
in
ecological
at
moonlight
the
[upper]
squid
lost.
are
travel
Cells
THE
populations
light
cavity
mantle
amechanism.
looking
Careful
presents
initiate
epithelia,
center.
the
aand
bacterium
active
viewed
Extension
images
acquired,
enter
radiate
(melanophores)
light
with
an
shadow
early
environment
more
squids
life-long
symbiont
at
from
water
seen
material.
are
EUPRYMNA
the
squid
within
an
bacteria
center
Margaret
intensity
symbionts,
its
hatches,
Simultaneously,
to
intightly
squid
organ
night,
its
that
outward
dispersal
aggregation
of
(Figure
cavity
mooncells
intimate
on
of
(Images
and
ciliated
Gram-negative
and
organ,
from
the
up
in
studies
were
attach
here
dispurse.
Animal
and
(a
that
specialized
light
the
aout
function
(Photo
own
this
bacterial
light
BACTERIA,
Vibrio
Specifically,
from
life:
hours
making
2.2.
E.
the
promptly
in
cell
Euprymna
of
in
uses
as
ventral
phenomenon
formation
SCOLOPESVIBRIO
symbiotic
light
the
or
below.
starlight
from
(Figure
life-long
obtained
McFall-Ngai
of
can
bacteria
to
Ziegelhoffer
Vibrio
this
the
A).
an
in
that
so
organ.
fascinating
courtesy
to
bacteria,
Physiology
below.
have
interaction
which
and
pores
organ.
from
treated
the
Acourtesy
of
acquire
fischeri.
that
be
the
further
key
and
bacterium
center
This
of
juvenile
surface
matches
hatching
Adispersal
light
perceived
revealed
B).
epithelia
fischeri
the
the
seawater
of
populate
Once
STUDY
shining
the
from
loss
squid
so
bacterial
the
skin
ofthat
acquisition
57between
produced
animal
acquired,
The
the
squid
INofinthe
its
CROSSPHYLUM
within
a codfish
microtubules
black-pigmented
(Gadusare
morhua)
visible. Pigm
granules are transported along the microtubules during dispersal and aggregation
ent
.In this
(b)
Diagram
cell,ofthe
a cell
blackinpigment
aggregated
granules
and dispersed
are aggregated
states.atNote
the that
cell the
center.
branched
shape of the cell ensures that pigment granules will be widely spread out when i
nthe dispersed state. (a photo courtesy of Hel n Nilsson Sk ld; from Nilsson and

58cell
(b)
(a)
Pigment
FIGURE
bobtail
long,
because
Diagrams
them,
(Figure
proteins
as
and
hormone)
fish
neuronally-stimulated
controls,
rhythms
The
Their
that
some
fully
molluscs
these
just
color-change
is
muscles
(e.g.,
imparting
Reception
Cells
throughout
cells
endocrine
disperse
MusclePigment
0.5
tracted.
pigment
Margaret
to
cell,
the
meaning
in
we
by
Extracellular
hormones
specifically
ligand
site
molecular
ligand-gated
enzyme-linked
Receptors
This
most
molecules
pass
entering
membrane
aeffects.
such
properties
LIGAND-GATED
protein
of
inorganic
9Table
further
Chapter
the
disperse
(i)
squids,
chromatophores
asurrounded
release
appropriate
address
binding
channel
AColor-change
(ii)
most
muscle
muscleswhich
mm
pigment
signal.
are
in
species
been
small,
(or
prevalence
signaling
through
molecules
young
accounting
whereas
color
light
organs
send
to
the
2.26
size
melanocyte-stimulating
0.1
of
at
2.1
cell
squid,
the
2.25b).
of
amphibians,
cells
mechanisms
molecules
that
showing
such
several
in
also
rapid
is
contract,
or
(b)
McFall-Ngai;
initiate
sites)
cells,
surface,
Only
chromatophores
discussing
its
and
cells,
cell
the
conformation
response
may
in
are
meaningful
ions,
2It
pigment
cuttlefish,
cells
mm
signals
the
glucose
signal
to
of
opens
defines
squid
Color-change
of
muscles
or
crustaceans.
change
coloration
mediated
inside
aggregate
barely
cell
ofthe
organ
that
organs
are
Relaxation
and
channels,
the
CHANNELS
acts
movement
as
directly
(in
in
color
Use
cell
contain
signals
receptor
signaling
receptor.
be
receptors,
proteins
hydrophobic
Euprymna
the
aggregate
color
body.
must
ways
molecules
bind
ato
Movement
on
of
these
through
organ
afor
kinesin
well-defined
often
innervated
allows
diameter;
(to
employing
so
in
noncovalently
categorized
first
hydrophobic
with
an
three
can
reception
their
of
and
four
as
animal.
color-change
movement
is
to
employing
visible
into
by
receptors
the
ofboth
fish,
is
consists
it
this
have
also
in
to
create
change
individual
by
ain
Signals
Nerve
the
rates
responses.
based
be
spread
each
pigment
yellow
b,c
which
initiate
signaling
Athe
(c)
muscles
toward
innervated,
and
in
called
entirely
diameter
the
has
response
proteins
receptor
of
(2)
three
or
intracellular
principal
functional
scolopes.
tiny
dimensions)
of
molecules
actions
Ligand
ligand-gated
the
organs
large
is
their
Chromatophores
in
very
case
mechanisms
have
cell,
and
cannot
and
less
after
the
cell.
other
receptors
aor
Color-change
The
color-change
octopusesthe
Figure
integument.
other
cells,
hormones,
the
Gsize.
athrough
driven
some
controlled
in
on
preceding
directly
pigment
blood.
it
and
receptor
cell
dynein.
color-change
of
out
by
neurotransmitter
prominent
or
into
proteincoupled
(4)
categories
at
interior
very
passageway
the
hormone
peptide
crustaceans.
chromatophores,
fast
granules,
contains
mechanisms
protein,
relaxed
size
pigment
the
an
than
muscles
modifies
their
called
to
binding
inmembrane
organ
can
adifferent
of
Cells
brown
Bozler
to
transduction.
on
protein
the
enter
hydrophilic
molecules
Incategories
crustaceans
and
that
(c)
intracellular
classes
The
cell
entirely
pigment
2.26b).
for
asuch
four
small
squid
by
poising
animal
(as
1.5
aWhen
the
addition
1switch
by
of
receptor
cell
then
Chromatophores
from
easily
signal
Contraction
effects
cell
receptors.
channel
and
entire
with
ATP-using
in
hormones
s!
paragraphs).
serve
example,
pigments.
receptors.
cells.
of
with
the
cells,
center
granules
by
dozens
is
mm
allows
effect
red
1928.)
signal
extracellular
as
aoccurs
functional
cell
organ
organs
ain
its
and
reside
signaling
for
(a)
amphibians
cephalopod
Color
to
process
surface
the
mediate
aof
biological
kingdom
organs
from
cell
the
By
typical
in
signal
neurotransmitters
by
bind
when
color-change
muscles
some
them
different
It
from
pigment,
channel.9
muscles
contract
visible
to
chromatophores
they
signal
intracellular
results
molecules
membrane;
receptors.
specific
Aat
squid
to
exhibit
contrast,
some
binding
protein
receptors,
For
cell
is
of
seen
aggregates
occurs
although
of
brain.
molecules.
the
on
reception
juvenile
are
(e.g.,
change
of
coordinate
signal
receptors
in
to
the
intracellular
by
for
exhibiting
(Photo
aNow
membrane
(Figure
radially
signal
of
integumentary
aAarrives
that
reflects
the
their
isrecep
fully
variable
of
cases)
pigment
classes:
the
membrane.
receptors
molecules
cell-membrane
islets
here,
contracted.
relaxed
hormones,
usage
Each
transduction
molecule
specific
contracted
are
and
relatively
molluscs.
(Figure
the
neighboring
in
intrinsic
clocks.
displayed
principle
so
Relaxation
to
muscles)expands
signal.
with
is
most
This
solutes,
only
red-pigmentconcentrating
in
muscle
sets
cell
that
once
this
contraction
ain
intracellular
Hawaiian
organs
signaled
fish
rapidly
dark
of
minimal
liver
muscles
to
considered
(3)
are
them
cephalopod
2.26a;
we
so
Moreover,
at
change
(Figure
proteins.
arranged
acell
activities
certain
the
part,
discuss
sort
2can
and
extrinsic
the
size
to
detect
in
(1)
membrane.
are
inside,
usage
have
2.26c),
acourtesy
or
that
receptor
enzyme/
Instead
on
mmtypically
expanded
such
to
Here
motor
cells
target
motion
fact
relative
(b,c)
confast
than
functions
to
color.
unable
the
a2.27).
that
of
size
expands
in
signaling
enter
binds
contract
the
aofofofto
the
that
cellAlthough

(a) Ligand-gated
Molecules
and Cells
channel
in Animal
(b) GPhysiology
proteincoupled
59
receptor and associated G protein s
ystem
(c)
Cell
Na+
K+
channels
when
alters
After
ATP
membrane
to
second
GKEY
coupled
Activation
GTP
interaction
Activating
catalytic
cell
cyclic
In
example,
activates
site
molecule.
active
Activated
(second
GMP
Cyclic
FIGURE
messenger)
in
example
proteincoupled
symbolized
later
themselves
other
with
cell.
which
single
site.
can
is
composed
binding
AMP
guanosine
steroid
dissolves
through
membrane.
complex
aligandreceptor
inside
Extracellular
Nuclear
Cytoplasm
(d)
Ligand
receptor
Intracellular
DNA
Nucleus
(simplified)
tor
as
mostly
narrow
and
carry
neurotransmitter
across
the
open
The
protein
protein
ligand
transcription
their
this
acell
diagrammed
Enzyme/enzyme-linked
activate
catalytic
enzyme
second
ligand
dissolve
receptor
=the
ligand,
activated
Intracellular
site
muscle
receiving
opened
membrane
they
causes
on
the
steroid
transcription
because
binding
in
membrane
The
is
(d)
cyclic
signals
AMP
messenger
siteLigand
GMP.
site
(first
2.27
protein
in
spaces
the
relatively
signaling
shown,
with
activated
hormone,
the
functions
envelope
typical
open
typically
proteinsa
binding
molecule
this
ligand
particularly
of
or
bind
Enzyme
site
example
Intracellular
After
monophosphate;
in
the
electrical
produces
or
cell.
of
amessenger
by
enzymes
nucleus.
cells
gap
channels
production
same
aThe
in
cell
sites
intracellular
catalytic
in
to
hormone
DNA.
adenosine
and
of
toto
activity
another
the
chapter.
hormone-binding
fluid
in
transmission
between
across
cell
ainside
proteins
with
this
four
receptor.
activates
aand
initiate
factor
binding
mode
permit
its
with
muscle
diffuses
Figure
(see
is
their
(first
(a)
at
yellow,
shown
ligand
Binding
hormonereceptor
as
receptor
on
the
interacts
simple
or,
factor.
is
Gsynapses
both
diffuse
case
released
permit
ligand,
types
two
receptor,
the
ofmonophosphate;
charge
protein
Athe
simple
interacting
Chapter
receiving
that
ofof
(c)
when
ions
ligands.
ligand-gated
cell
that
is
receptors
2.27a.
receptor
functioning,
messenger)
sites
enters
cellular
aGTP
protein
Details
double-headed
an
with
enzyme
Enzyme/enzyme-linked
ligand-binding
ATP
of
ligand-gated
the
increased
activated,
through
toare
aacross
with
acetylcholine
are
enzyme
=because
by
and
receptor
region
nerve
13).
Gcell.
for
aatrial
=the
guanosine
Ligand-gated
neurotransmitter
pass
the
one
The
proteincoupled
enzymes.
type
adenosine
bind
two
an
catalytic
of
are
responses.
nerve
called
the
hormone
complex
The
catalytic
the
cell,
impulses
cell
through
enzyme
channel.
the
it
and
flux
ligand-gated
other
natriuretic
effective
of
cyclic
to
The
proteins
channel
interact
signaling
membrane.
arrows
consists
lipid
cells
channels
molecular
areceptor
triphosphate.
specific
neurotransmitters.
into
Either
site
it
initial
of
receptor,
region
activates
functions
triphosphate;
cellsites.
channels
ions
forms
The
GMP
across
inorganic
The
site
bilayer
aor
toto
are
and
involved
receptors
directly
only
synaptic
way,
of
=example
between
molecules
in
particular
open.
peptide
protein
capable
signaling
response
interactions
discussed
ainside
cyclic
the
just
synapses,
its
must
catalytic
for
complex
the
function
binding
of
channels.
ions
(b)
cell
awith
ligands
the
shown
receptor,
cyclic
nerve
gap,
bind
are
the
receptor,
that
of
that
of
Amembrane
molecules,
When
cell
with
Gisdiffuses
the
it
athat

Cytoplasm
60
NORMAL
Muscle
fluid
Extracellular
membrane
End
.-conotoxin
nerve
acetylcholine
Open
Acetylcholine
In
aChapter
ofnormal
cell
POISONED
cell
Closed
2fish,
receptor
when a nerve cell releases acetylcholine, the In a poisoned fi
sh, thecell
muscle
muscle
receptors
cell receptors
bind theare
acetylcholine,
unable to bind
causing the the acetylcholine beca
use the receptor
receptors,
which are
sitesligand-gated
are blockedchannels,
by the to open, thereby .-conotoxin. The re
ceptors thusthe
stimulating
failmuscle
to open
cellintothecontract.
normal way.
Consequently, the muscle cell is not st
imulated
contractthe
Closed
across
An
specific
cell
receptorswhich
muscle
Fish-eating
A(a)
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Go
for
and
Alberts,
References
Molecular
treatment
the
Aspengren,
into
Rev.
subject
within
Feder,
chaperones,
physiology.
Fields,
Localized
A4
Acad.
Glickman,
pathway:
373428.
Chapter
overview
already
Cells
It
modern-day
Using
say
animal
Pollutants
HAHs
them.
Explain
Describe
Venoms
What
Outline
to
orthologs
incomponent.
receptors
and
or
Present
Cone
cellular
box
other
topics
expression,
fall
through
notably
with
sequence
in
if
melanosome
Cell.
these
enzymes,
by
cell
cells
Questions
is
amounts
sure
become
sites.sinauer.com/animalphys3e
Sci.
messengers
The
transduction
motion
extracellular
functional
cyclic
messengers,
any
that
2.21a,
have
chromatophores.
M.
or
K+,
spotty
be
is
aevolutionary
in
are
extensions,
followed
P.
in
signal-amplifying
binding
proteins
results
amplification
genes.
becoming
might
lactate
Suppose
fluidity.
rather
properties
channels,
snails,
B.,
destruction
intracellular
Ginto
and
by
the
nuclear
organization.
more
nearly
venom
resources.
Biology
of
E.,
increases
M.
2U.S.A.
present
proteins
function
Extracellular
protein
particularly
cooperativity,
why
of
only
the
to
in
S.,
Mol.
A.,
of
compounds
intracellular
because
proteincoupled
across
may
multiple
present,
the
your
additional
independently
and
Annu.
the
cell
of
their
aprotein
mechanisms
A.
its
H.,
Use
cell
for
nitric
formation
GMP,
effects
enzymes
such
sites
metabolic
of
consider
and
receptor.
this
some
but
three
you
in
harbor
Gpristine
functional
target
D.
and
signals
ligand-gated
Gthen
receptors,
possible
than
is
about
Johnson,
transport
Biol.
the
Antarctic
or
noncovalently
hydrophobic,
ain
dehydrogenase
you
proteinmediated
always
individual
views
krait
subject,
by
and
share
activated
these
membranes,
class:
proteincoupled
DNA
possible
their
explain
of
Hedberg,
G.
Rev.
95:
kinase
they
signal
cell
the
extracellular
on
in
desired.
now-nonexistent
obtain
as
composed
and
chapter.
G.
prominent
by
virtually
pathways
to
they
changed
affect
exist?
quizzes,
details
stress
in
Signals
signaling
principal
oxide
trigger
kinases.
fish
want
and
pure
the
E.
A.
for
participate.
the
turn,
in
and
(e.g.,
molecular
halogenated
are
half
of
272:
N.
1147611481.
phosphorylation.
be
membranes.
of
on
the
receptors.
plausible
snakes,
Physiol.
conformational
with
effect
may
such
molecules
membranes,
of
distributions
harbor.
useful
pathways.
consist
Why
involved.
Hofmann.
Ciechanover.
are
signaling
intracellular
which
roles
physiological
venoms?
J.
Cell,
Somero.
the
cell
then
membranes,
transduction
altered.
inside
directly
by
might
to
in
and
compounds.
the
roles
which
evolved
including
notothenioid
reactions
(NO),
second
when
for
each
the
Explain
various
H.
245302.
response:
be
by
receptors,
fluxes
often
Suppose
components;
of
do
Lewis,
on
cyclic
involving
as
hydrophilic,
such
channels
other
Figure
synthesizing
determine
fact
flashcards,
vertebrate
sake
second-messenger
any
Alipid
ultimate
why
two
N.
is
in
activates
cell-membrane
with
binding
molecules
functional
preexisting
molecular
as
for
of
two
quantity
and
you
5th
mechanisms
hormones
function
activated
forms
be
Why
other
of
tree
61:
have
signaling
of
family
Explain
Sk
1999.
1998.
to
other
are
as
The
receptors
messengers,
trigger
an
aromatic
more
does
receptor
allosteric
sides
venoms
of
For
molecules
of
thereby
effects.
activate
ancestral
able
your
complex
compounds,
and
conformational
categories
poison-dart
suppose
M.
ed.
AMP
specific
interior
the
you
2.21b)
might
advanced
Ald,
243282.
activate
inactive
transcription
are
steroid
example,
Assume
you
Evolutionary
2002.
construction.
cell-membrane
receptors
by
inorganic
altered
of
in
directly?
Raff,
fine,
flexibility
the
second
with
mechanisms
and
receptors.
effect.
if
exposed
it
reasons
justify.
Garland,
Heat-shock
Hot
fishes.
the
The
sort
cell
use
to
purposes?
for
than
of
trees
pigment
and
aornot
initiate
are
their
of
biologists
enzymes
bodies
judge
that
your
or
classes:
sequences
by
athe
of
most
common
enzyme/enzymelinked
altering
ligands
enzymes
to
hydrocarbons
avoid
systems
mixes
the
this
spots
The
property
inactivates
target
their
and
these
aspecific
study
that
instance,
K.
general
M.
channels
receptor
chemically
otherwise
of
that
hormones,
membrane.
their
enzyme
modulation
if
discussion
pigment
aRoberts,
form,
messengers.
voltage
such
phylogenetic
predict
ancestral
explain
fish
require
each
of
for
block
answer
systems
ligands
why
debate
to
frogs
Proc.
ubiquitin-proteasome
Wallin.
part,
protein
protein.
cell
that
ions,
enzyme/enzymelinked
of
it
receptor
New
cells.
occur
being
of
mixes
proteins
in
feature
their
signal
that
readily
sequences
HAHs
of
changes
the
be
proteins,
and
in
proteins
factors
ligand-gated
typically
as
are
ligands,
water.
living
depend
mixes
will
alone
Physiol.
as
proteins
voltage
of
to
form.
compounds.
the
York.
introduction
cold
that
membranes.
belong
primaryliver
most
(dendrobatid
in
transport
lactate
Natl.
all
or
proteins.
such
cyclic
the
why
that
assume
over
enzyme
ecological
in
Figure
ultimately
unable
thyroid
most
The
additional
modulated,
synthesize
at
exposed
than
imply
Int.
2008.
kinase
its
actions
unable
enzyme
(HAHs)
in
be
muscle
terms
and
of
receptors,
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ligands
are
were
has
adaptation:
their
of
amino
What
it
all
Thus,
on
in
such
Alikely.
that
as
tree
P450
the
whether
many
target
are
to
is
usually
P.
peerless
molecular
Rev.
the
is
an
proteins,
forms
so
dehydrogenase
New
2.30
to
levels
the
of
that
ato
are
as
Walter.
regulate
on
true
even
of
to
82:
insights
ofthe2007.
in

Molecules
Golding,
adaptation.
introduction
Hardison,
An
including
regions
Hochachka,
Mechanism
Press,
adaptation
Pedagogically
Hofmann,
marine
Comp.
King,
misfolding.
Lodish,
H.
W.
Olivera,
receptor
Powers,
agene
challenging
the
ecological
Somero,
animals:
42:
Viviani,V.
of
Widder,
chemical,
compact
production
Wirgin,
E.
tomcod
argues
intracellular
polychlorinated
NOTE:
system
with
See
changing
accessible
Ploegh,
H.
neuropharmacology.
the
insect
Hahn.
million-year
molecular
780789.
also
structure
the
Biol.
J.,
AFreeman,
New
organisms
future
from
that
was
ofAdditional
H.,
D.
G.
E.
reviewwith
I.,
truly
G.and
B.
and
Optima,
2011.
year
R.authored
studies
C.
luciferases.
DNA,
P.
York.A
written
and
A.,
environment:
relationships
N.
R.
A.
by
B.,
Mol.
E.
45:
Am.
A.
M.
paper
N.
the
rapid
to2000
1999.
Haase-Pettingell,
ion
Cells
treatment
W.,
Process
exceptional.
physiology
of
2002.
2002.The
2010.
ecological
marine
receptor
marvelous
2005.
Berk,
P.
New
1997.
and
K.
Mechanistic
and
the
as
247255.
Sci.
Hudson
biphenyls.
Biol.
on
channel
saga
environmental
limits,
ofawards
and
peerless
Matsudaira.
records
Roy,
evolutionary
The
well
by
York.
P.
expression
inanimals.
A.
new
small
Thermal
Bioluminescence
many
by
References
the
Patterns
90:
C.
E.
G.Michael
in
two
Mol.
M.
of
Animal
Evol.
evolution
origin,
Cell.
M.
River.
protein
field
of
as
A.
AE.
historical
evolution
N.
Physiological
445453.
targets,
aSchulte.
of
and
diversity.
informative
Dean.
of
to
multidisciplinary
one
Loftus,
at
research
coding
review
Kaiser,
Just
Biol.
small
basis
aSomero.
physiology
15:
large
evolutionary
costs
Mol.
the
Physiology
2007.
in
of
species.
Science
physiology.
diversity,
increase
provides
S.
and
1998.
Lecture,
355369.
paleomolecular
foremost
Hsp
Cell
natural
fish.
the
of
Lasker
regions.
of
and
1998.
Life
R.
Brown
biogeographic
D.
M.
of
account
Figure
hemoglobin.
on
2002.
Molecular
in
Science
resistance
the
gene
most
imagesof
C.
The
the
Gossard.
Krieger,
drug
8:
living.
331:
Evolution.
J.
There
and
Sci.
the
Evolutionary
Chambers,
in
resistance
and
Foundation
65and
modern
1996.
21012109.
populations
Astructural
relevant
Biochemical
scientists
expression
Exp.
successful
biology
evolution
design:
vertical
ocean:
13221325.
frequency
of
daring
approach
59:
328:
can
isTable
Cell
Integr.
structure
the
2002.
M.
Conus
Zool.
light
to
biochemistry.
Am.
study
probably
18331850.
be
scales.
704708.
Oxford
P.
of
origins
D.
PCBs
ubiquitinproteasome
and
promoter
Biology,
50
to
read
website.
Sci.
zonation
Citations
basis
Protein
Scott,
venom
adaptations
in
to
282:
efforts
the
G.
of
Adaptation:
of
million
Comp.
This
toxic
thought-provoking
in
the
ectothermic
relation
address
function
aFranks,
87:
University
biochemical
Integr.
no
protein,
7194.
of
An
Atlantic
mutated
ofeffects
peptides,
paper
and
field.
A.
6th
better
Biol.
126137.
folding
to
of
biological,
articulate,
molecular
years
Bretscher,
enhancer
ed.
understand
intertidal
and
ofexemplar
to
This
relationships
M.and
of

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