Física do Corpo Humano
Prof. Adriano Mesquita AlencarDep. Física Geral
Instituto de Física da USP
Ribbon, Transporte Ativo, Enzimas e geradores de energia B02
Diagrama de Ribbon
126 Chapter 3: Proteins
methionine (Met)
T f oO l l / zH - : N - C - C| \._o
H ( i l \ J
I( H ,I5
( - H ,
(.'1( ) ( )\i. (
f ' l oot , / lH o: N - c - c +
I I \^O
leucine (Leu)
H C . U , oI
( ' H/ / \
H,( ' Cl-J J
H:O
( ) t l
( | l ,I- c -I
H
tyrosine (Tyr)
Hzo
carboxyl terminusor C-terminus
o-C\ o
HI
-^Nt l
H
H
polypept ide backbone s ide cha ins
H , ( - ( l - l I
Figure 3-1 The componentsof a protein. A proteinconsists of a polypeptidebackbone with attached sioechains. Each type of proteindif fers in i ts sequence andnumber of amino acids;therefore, it is the sequenceof the chemical ly dif ferentside chains that makes eachprotein dist inct. The two endsof a polypeptide chain arechemical ly dif ferent: the endcarrying the free amino group(NH3+, also writ ten NH2) is theamino terminus, orN-terminus, and that carryingthe free carboxyl group(COO-, also written COOH) isthe carboxyl terminus orC-terminus. The amino acidsequence of a protein isalways presented in theN-to-C direct ion, readingfrom left to rioht.
I I
( ) t l
H H O^ t t t l
Hei- i -3r lH l( H ,I
( - H ,I5
( H ,
o vamino t e rm inusor N-terminus C
\ o
oono
SCHEMATIC
SEQU ENCE Met Asp
As discussed in chapter 2, atoms behave almost as if they were hard sphereswith a definite radius (their uan derwaals radius). The requirement that no twoatoms overlap limits greatly the possible bond angles in a pollpeptide chain(Figure 3-3). This constraint and other steric interactions severely restrict thepossible three-dimensional arrangements of atoms (or conformaflons). Never-theless, a long flexible chain, such as a protein, can still fold in an enormousnumber of ways.- The folding of a protein chain is, however, further constrained by many dif-ferent sets of weak noncoualent bonds that form between one part of the chainand another. These involve atoms in the polypeptide backbone, as well as atomsin the amino acid side chains. There are three tlpes of weak bonds: hydrogenbonds, electrostatic attractions, and uan der waals .tttractions, as explained inchapter 2 (see p. 54). Individual noncovalent bonds are 30-300 times weakerthan the tlpical covalent bonds that create biological molecules. But manyweakbonds acting in parallel can hold two regions of a polypeptide chain tightlytogether. In this way, the combined strength of large numbers of such noncova-lent bonds determines the stability of each folded shape (Figure 3-4).
Tyr
polypept ide backbone
Diagrama de Ribbon1 3 0 Chapter 3: Proteins
g lu tam ic ac i d
electrostaticattractions
//o H
Figure 3-4 Three types of noncovalentbonds help proteins fold. Although asingle one of these bonds is quite weak,many of them often form together tocreate a strong bonding arrangement, asin the example shown. As in the previousfigure, R is used as a general designationfor an amino acid side chain.
Figure 3-5 How a protein folds into acompact conformation, The polar aminoacid side chains tend to gather on theoutside of the protein, where they caninteract with water; the nonpolar aminoacid side chains are buried on the insideto form a tightly packed hydrophobiccore of atoms that are hidden from water.In this schematic drawing, the proteincontains only about 30 amino acids.
R
H
N- C H ,
t -CH,t -
C H tt -
Proteins Fold into a Conformation of Lowest EnergyAs a result of all of these interactions, most proteins have a particular three-dimensional structure, which is determined by the order of the amino acids in itschain. The final folded structure, or conformation, of any polypeptide chain isgenerally the one that minimizes its free energy. Biologists have studied proteinfolding in a test tube by using highly purified proteins. Treatment with certain
sequence contains all the information needed for specifying the three-dimen-sional shape of a protein, which is a critical point for understanding cell function.
Each protein normally folds up into a single stable conformation. However,the conformation changes slightly when the protein interacts with othermolecules in the cell. This change in shape is often crucial to the function of theprotein, as we see later.
Although a protein chain can fold into its correct conformation without out-side help, in a living cell special proteins called. molecular chaperones often assistin protein folding. Molecular chaperones bind to partly folded polypeptidechains and help them progress along the most energetically ravoriute-rolaing
-*<_
hydrogen bond
hydrophobiccore regtoncontainsnonpotars ide chains
polar s ide chainson the outs ideof the moleculecan form hydrogenbonds to water
van der Waals attractions
t n ' :
unfolded polypeptide folded conformation in aqueous envtronment
Diagrama de Ribbon134 Chapter 3: Proteins
amino acids i de cha in
Figure 3-7 The regular conformation of the polypeptide backbone in the cr helix and the p sheet. <GTAG> <TGCT>(A, B, and C) The o helix. The N-H of every peptide bond is hydrogen-bonded to the C=O of i neighboring peptide bondlocated four peptide bonds away in the same chain. Note that al l of the N-H groups point up in this diagIm and that al l ofthe C=O groups point down (toward the C-terminus); this gives a polari ty to the hel ix, with the C-terminus having a part ialnegative and the N-terminus a part ial posit ive charge. (D, E, and F) The F sheet. In this example, adjacent peptide chainsrun in opposite (antiparal lel) direct ions. Hydrogen-bonding between peptide bonds in dif ferent strands holds tneindividual polypeptide chains (strands) together in a B sheet, and the amino acid side chains in each strand alternatetyproject above and below the plane ofthe sheet. (A) and (D) show al l the atoms in the polypeptide backbone, but theamino acid side chains are truncated and denoted by R. In contrast, (B) and (E) show the backbone atoms only, while (C)and (F) display the shorthand symbols that are used to represent the s hel ix and the B sheet in r ibbon drawings of proteins(see Panel 3-28).
(c)
Iil l
l i
Diagrama de Ribbon
134 Chapter 3: Proteins
amino acids i de cha in
Figure 3-7 The regular conformation of the polypeptide backbone in the cr helix and the p sheet. <GTAG> <TGCT>(A, B, and C) The o helix. The N-H of every peptide bond is hydrogen-bonded to the C=O of i neighboring peptide bondlocated four peptide bonds away in the same chain. Note that al l of the N-H groups point up in this diagIm and that al l ofthe C=O groups point down (toward the C-terminus); this gives a polari ty to the hel ix, with the C-terminus having a part ialnegative and the N-terminus a part ial posit ive charge. (D, E, and F) The F sheet. In this example, adjacent peptide chainsrun in opposite (antiparal lel) direct ions. Hydrogen-bonding between peptide bonds in dif ferent strands holds tneindividual polypeptide chains (strands) together in a B sheet, and the amino acid side chains in each strand alternatetyproject above and below the plane ofthe sheet. (A) and (D) show al l the atoms in the polypeptide backbone, but theamino acid side chains are truncated and denoted by R. In contrast, (B) and (E) show the backbone atoms only, while (C)and (F) display the shorthand symbols that are used to represent the s hel ix and the B sheet in r ibbon drawings of proteins(see Panel 3-28).
(c)
Iil l
l i
Diagrama de Ribbon
c
3-5
o
o
oEf
(J
(D) Space-filling: Provides contour map of the protein; gives a feel for theshaoe of the protein and shows which amino acid s ide chains are exposedon its surface. Shows how the protein might look to a small molecule,such as water, or to another protein.
(C) Wire: Highl ights s ide chains and their re lat ive proximit ies; useful forpredict ing which amino acids might be involved in a protein 's act iv i ty ,part icular ly i f the protein is an enzyme.
Diagrama de Ribbon
THE
SH
AP
E AN
D S
TRU
CTU
RE
O
F P
RO
TEIN
S
can
be re
adily
link
ed in
ser
ies t
o fo
rm e
xten
ded
stru
ctur
es-e
ither
w
ith t
hem
-se
lves
or w
ith o
ther
in-li
ne d
omai
ns (
Figu
re 3
-f7).
Stiff
ext
ende
d st
ruct
ures
com
pose
d of
a s
erie
s of d
omai
ns a
re e
spec
ially
com
mon
in e
xtra
cellu
lar m
atrix
mol
ecul
es a
nd in
the
ext
race
llula
r por
tions
of
cell-
surfa
ce re
cept
or p
rote
ins'
Oth
er m
odul
es, i
nclu
ding
the
SH2 d
omai
n an
d th
e kr
ingl
e do
mai
n ill
ustra
ted
inFi
gure
3-1
6, a
re o
f a "p
lug-
in"
typ"
, with
the
ir N
- an
d C
-term
ini c
lose
toge
ther
.Af
ter g
enom
ic re
arra
ngem
ents
, suc
h m
odul
es a
re u
sual
ly a
ccom
mod
ated
as a
nin
serti
on in
to a
loop
regi
on o
f a s
econ
d pro
tein
.A
com
paris
on o
f the
rel
ativ
e fre
quen
cy o
f dom
ain
utili
zatio
n in
diff
eren
teu
cary
otes
reve
als t
hat,
for
man
y co
mm
on d
omai
ns, s
uch
as p
rote
in k
inas
es,
this
freq
uenc
y is
sim
ilar
in o
rgan
ism
s as
div
erse
as y
east
, pla
nts,
wor
ms,
flie
s,an
d hu
man
s (F
igur
e 3-
f 8).
But t
here
are
som
e no
tabl
e ex
cept
ions
, suc
h as
the
Maj
or H
isto
com
patib
ility
C
ompl
ex (
MH
C)
antig
en-r
ecog
nitio
n do
mai
n (s
eeFi
gure
25-
52) t
hat
is p
rese
nt in
57
copi
es in
hum
ans,
but
abs
ent i
n th
e ot
her
four
org
anis
ms
just
men
tione
d. S
uch
dom
ains
pre
sum
ably
hav
e sp
ecia
lized
func
tions
that
are
not
sha
red w
ith t
he o
ther
euc
aryo
tes,
bein
g st
rong
ly s
elec
ted
for d
urin
g ev
olut
ion
so a
s to
give
rise
to th
e m
ultip
le c
opie
s obs
erve
d. S
imila
rly,
a do
mai
n lik
e SH
2 th
at s
how
s an
unu
sual
incr
ease
in i
ts n
umbe
rs in
hig
her
euca
ryot
es m
ight
be
assu
med
to b
e es
peci
ally
usef
ul fo
r mul
ticel
lula
rity
(com
-pa
re th
e m
ultic
ellu
lar
orga
nism
s with
yea
st in
Fig
ure
3-18
).
Cer
tain
Pai
rs of
Dom
ains
Are
Foun
d Tog
ethe
r in M
any P
rote
ins
We c
an co
nstru
ct a
larg
e tab
le d
ispl
ayin
g dom
ain
usag
e for
eac
h org
anis
m w
hose
geno
me
sequ
ence
is k
nor,r
,rr. F
or e
xam
ple,
the
hum
an g
enom
e is
est
imat
ed t
oco
ntai
n ab
out 1
000 i
mm
unog
lobu
lin d
omai
ns, 5
00 pr
otei
n ki
nase
dom
ains
, 250
DN
A-bi
ndin
g ho
meo
dom
ains
, 300
SH
3 dom
ains
, and
120
SH
2 dom
ains
. Im
por-
tant
add
ition
al in
form
atio
n ca
n be
der
ived
by
com
parin
g th
e fre
quen
cies
and
arra
ngem
ents
of
dom
ains
in
the
mor
e th
an 1
00 e
ucar
yotic
, bac
teria
l, an
dar
chae
al ge
nom
es th
at h
ave
been
com
plet
ely
sequ
ence
d. Fo
r exa
mpl
e, w
e fin
dth
at m
ore
than
two-
third
s of
pro
tein
s co
nsis
t of t
wo
or m
ore
dom
ains
, and
that
the
sam
e pa
irs o
f dom
ains
occ
ur re
peat
edly
in th
e sa
me
rela
tive
arra
ngem
ent i
na
prot
ein.
Alth
ough
hal
f of a
ll do
mai
n fa
mili
es a
re co
mm
on to
arc
haea
, bac
teria
,an
d eu
cary
otes
, onl
y ab
out 5
per
cent
of t
he tw
o-do
mai
n co
mbi
natio
ns a
re si
mi-
larly
sha
red.
This
pat
tern
sug
gest
s that
mos
t pro
tein
s co
ntai
ning
esp
ecia
lly us
e-fu
l tw
o-do
mai
n co
mbi
natio
ns a
rose
rela
tivel
y la
te in
evo
lutio
n.Th
e 20
0 m
ost
abun
dant
tw
o-do
mai
n co
mbi
natio
ns o
ccur
in a
bout
one
-fo
urth
of a
ll of
the
prot
eins
with
rec
ogni
zabl
e dom
ains
in th
e co
mpl
ete
data
set.
It w
ould
the
refo
re b
e ve
ry u
sefu
l to
dete
rmin
e th
e pr
ecis
e th
ree-
dim
ensi
onal
stru
ctur
e fo
r at l
east
one
prot
ein
from
eac
h com
mon
two-
dom
ain
com
bina
tion,
so a
s to
reve
al ho
w th
e do
mai
ns in
tera
ct in
that
type
of p
rote
in s
truct
ure.
46
42
38
34
30
26 z z 18
14
10
06
02
*J
141
c o o c a E E o c 6 l o o a a
./ f'
\-\
^a"
\c s
(A)
(B)
Figu
re 3-
1 7 A
n ex
tend
ed st
ruct
ure
form
ed fr
om a
serie
s of i
n-lin
e pro
tein
mod
ules
. Four
f ibro
nect
in type
3 m
odul
es(s
ee Fi
gure
3-16
) from
the e
xtra
cel lu
lar
mat
rix m
olec
ule f i
bron
ectin
are i
l lust
rate
din
(A) r i
bbon
and (
B) s
pace
-fi l l
ing m
odel
s.(A
dapt
ed fro
m D
.J. Le
ahy,
l. Auk
hil a
ndH
.P. Er
icks
on, Cel
l84:
155-
164,
1996
. With
oerm
issi
on from
Els
evie
r.)
Figu
re 3-
18 T
he re
lat iv
e freq
uenc
ies of
thre
e pr
otei
n do
mai
ns in
five
euc
aryo
ticor
gani
sms.
The a
ppro
xim
ate p
erce
ntag
esgi
ven h
ave b
een d
eter
min
ed by
divi
ding
the
num
ber o
f cop
ies o
f eac
h dom
ain b
yth
e tot
al nu
mbe
r of d
ist in
ct pr
otei
nsth
ough
t to
be en
code
d bY e
ach
orga
nism
, as de
term
ined
from
the
sequ
ence
of i t
s gen
ome.
Thus
, for 5
H2
dom
ains
in h
uman
s, 12
0/24
,000
=
0.00
5.
.f tr'
I."d
ot "s
.c
euca
ryot
ic pr
otei
n ki
nase
DN
A-b
indi
ng ho
meo
dom
ain
SH
2 dom
ain
Diagrama de RibbonRepresentação de
Proteínas em em 3D✴representação mais comum✴organização do caminho
✴espinha dorsal da proteína✴α-helices (ribbons mola)✴β-strands (setas)✴metais (esferas)
http://www.rcsb.org/pdb/home/home.do
Meios de Transporte
656 Chapter 1 1: Membrane Transport of Small Molecules and the Electrical Properties of Membranes
Il le lectrochemical
qradient- i t
Figure 1 I -7 Three ways of driving activetransport. The actively transportedmolecule is shown in yel low, and theenergy source is shown in red.
Figure 1 I -8 Three types of transporter-mediated movement. <ACCC> Thisschematic diagram shows transportersfunctioning as uniporters, symporters,and antiporters.
COUPLEDTRANSPORTER
ATP-DRIVENPUMP
LIGHT-DRIVENPUMP
Active Transport Can Be Driven by lon Gradients
same direction, performed by symporters (also called co-transporters), or thetransfer of a second solute in the opposite direction, performed by antiporters(also called exchangers) (Figure ll-8).
The tight coupling between the transfer of two solutes allows these coupled
gradient of which provides a large driving force for the active transport of a sec-ond molecule. The Na+ that enters the cell during transport is subsequentlypumped out by an ArP-driven Na+ pump in the plasma membrane (as we dis-cuss later), which, by maintaining the Na+ gradient, indirectly drives the trans-port. (For this reason ion-driven carriers are said to mediate second.ary actiuetransport, whereas ArP-driven carriers are said to mediate primary actiue trans-port.)
Intestinal and kidney epithelial cells, for example, contain a variety of sym-porters that are driven by the Na+ gradient across the plasma membrane. E'achNa*-driven symporter is specific for importing a small group of related sugars oramino acids into the cell, and the solute and Na* bind to different sites on thetransporter. Because the Na+ tends to move into the cell down its electrochemi-cal gradient, the sugar or amino acid is, in a sense, "dragged" into the cell with it.The greater the electrochemical gradient for Na+, the gieater the rate of solute
transported molecule co-t ransported ion
, / \
\I
ANTIPORT
-l ,,0,0
I uitaver
SYMPORT
ADP
UNIPORT
coupled t ransport
Transporte Ativo
656 Chapter 1 1: Membrane Transport of Small Molecules and the Electrical Properties of Membranes
Il le lectrochemical
qradient- i t
Figure 1 I -7 Three ways of driving activetransport. The actively transportedmolecule is shown in yel low, and theenergy source is shown in red.
Figure 1 I -8 Three types of transporter-mediated movement. <ACCC> Thisschematic diagram shows transportersfunctioning as uniporters, symporters,and antiporters.
COUPLEDTRANSPORTER
ATP-DRIVENPUMP
LIGHT-DRIVENPUMP
Active Transport Can Be Driven by lon Gradients
same direction, performed by symporters (also called co-transporters), or thetransfer of a second solute in the opposite direction, performed by antiporters(also called exchangers) (Figure ll-8).
The tight coupling between the transfer of two solutes allows these coupled
gradient of which provides a large driving force for the active transport of a sec-ond molecule. The Na+ that enters the cell during transport is subsequentlypumped out by an ArP-driven Na+ pump in the plasma membrane (as we dis-cuss later), which, by maintaining the Na+ gradient, indirectly drives the trans-port. (For this reason ion-driven carriers are said to mediate second.ary actiuetransport, whereas ArP-driven carriers are said to mediate primary actiue trans-port.)
Intestinal and kidney epithelial cells, for example, contain a variety of sym-porters that are driven by the Na+ gradient across the plasma membrane. E'achNa*-driven symporter is specific for importing a small group of related sugars oramino acids into the cell, and the solute and Na* bind to different sites on thetransporter. Because the Na+ tends to move into the cell down its electrochemi-cal gradient, the sugar or amino acid is, in a sense, "dragged" into the cell with it.The greater the electrochemical gradient for Na+, the gieater the rate of solute
transported molecule co-t ransported ion
, / \
\I
ANTIPORT
-l ,,0,0
I uitaver
SYMPORT
ADP
UNIPORT
coupled t ransportTRANSPORTERS AND ACTIVE MEMBRANE TRANSPORT 657
Na*
u * $stateA <- stateB
+ +
grucose
iiF fu. g. $Ell+
+' + ++ +
Na*electrochem ica I
g rad i ent
+ tra nsporter
entry; conversely, if the Na+ concentration in the extracellular fluid is reduced,solute transport decreases (Figure ll-9).
In bacteria and yeasts, as well as in many membrane-enclosed organelles ofanimal cells, most active transport systems driven by ion gradients depend onH+ rather than Na* gradients, reflecting the predominance of H+ pumps and thevirtual absence of Na+ pumps in these membranes. The electrochemical H+ gra-dient drives the active transport of many sugars and amino acids across theplasma membrane and into bacterial cells. One well-studied H+-driven sym-porter is lactose permease, which transports lactose across the plasma mem-brane of E. coli. Structural and biophysical studies of the permease, as well asextensive analyses of mutant forms of the protein, have led to a detailed modelof how the symporter works. The permease consists of 12 loosely packed trans-membrane cr helices. During the transport cycle, some of the helices undergosliding motions that cause them to tilt. These motions alternately open andclose a crevice between the helices, exposing the binding sites for lactose andH*, first on one side of the membrane and then on the other (Figure ll-10).
Transporters in the Plasma Membrane Regulate Cytosolic pH
Most proteins operate optimally at a particular pH. Lysosomal enzymes, forexample, function best at the low pH (-5) found in lysosomes, whereas cltoso-lic enzymes function best at the close to neutral pH (-7.2) found in the cytosol.It is therefore crucial that cells control the pH of their intracellular compart-ments.
Most cells have one or more tlpes of Na+-driven antiporters in their plasmamembrane that help to maintain the cltosolic pH at about 7.2. These trans-porters use the energy stored in the Na+ gradient to pump out excess H+, whicheither leaks in or is produced in the cell by acid-forming reactions. TWo mecha-nisms are used: either H+ is directly transported out of the cell or HCO3- isbrought into the cell to neutralize H+ in the cytosol (according to the reactionHCOa- + H+ -+ HzO + COz). One of the antiporters that uses the first mechanismis a Na+ -H+ exchanger,which couples an influx of Na+ to an efflux of H+. Another,which uses a combination of the two mechanisms , is a Nd -driuen Ct-HCOs-exchangerthat couples an influx of Na* and HCOS- to an efflux of Cl- and H* (so
+ + f u q h U lEXTRACELLULAR SPACE
+ + + + +
u q b @Figure 11-9 One way in which a glucose transporter can be driven by a Na+ gradient. As in the modelshown in Figure 11-5, the transporter osci l lates between two alternate states, A and B. In the A state, theprotein is open to the extracel lular space; in the B state, i t is open to the cytosol. Binding of Na* andglucose is cooperative-that is, the binding of either l igand induces a conformational change thatincr"ur", the protein's aff ini ty for the other l igand. Since the Na+ concentrat ion is much higher in theextracel lular space than in the cytosol, glucose is more l ikely to bind to the transporter in the A state.Therefore, both Na+ and glucose enter the cel l (via an A -+ B transit ion) much more often than they leave i t(via a B -+ A transit ion). The overal l result is the net transport of both Na+ and glucose into the cel l . Notethat, because the binding is cooperative, i f one of the two solutes is missing, the other fai ls to bind to thetransporter. Thus, the transporter undergoes a conformational switch between the two states only i f bothsolutes or neither are bound.
* - "lI I 'P',oDr rayer
gl ucosegrad ient
L]
Transporte Ativo
lactose
658 Chapter 1 1: Membrane Transport of Small Molecules and the Electrical Properties of Membranes
(A)
Figure 1 1 -10 The molecular mechanismofthe bacterial lactose permeasesuggested from its crystal structure.(A) The 12 transmembrane hel ices of thepermease are clustered into two lobes,shown in two shades of green. The loopsthat connect the hel ices on either side ofthe membrane are omitted for clari ty.During transport, the hel ices sl ide and t i l tin the membrane, exposing binding sitesfor the disaccharide lactose (yellow) andH+ to either side of the membrane. (B) Inone conformational state, the H+- andlactose-binding sites are accessible to theextracellular space (top row); in the other,they are exposed to the cytosol (bottomrow). Loading the solutes on theextracel lular side is favored becausearginine (R) 144 forms a bond withglutamic acid (E) 126, leaving E269 free toaccept H+. Unloading the solutes on thecytosolic side is favored because R1 44forms a bond with E269, whichdestabi l izes the bound H+. In addit ion,the lactose-binding site is part ial lydisrupted due to the rearrangement ofthe hel ices. Because the transit ionbetween the two protonated states(middle) is forbidden, H+ can only betransported when a lactose is alsotransported. In this way, theelectrochemical H+ gradient driveslactose import. (Adapted fromJ. Abramson et al. ,Sclence 301:610-615, 2003. With permission fromAAAS.)
lactose
144A
cE126
C E26e
proton
@-t*
T@
26c
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FORBIDDENTRANSITION
E 1
An Asymmetric Distribution of Transporters in EpithelialcellsUnderlies the Transcellular Transport of SolutesIn epithelial cells, such as those that absorb nutrients from the gut, trans-porters are distributed n_onuniformly in the plasma membrane and therebycontribute to the transcellular transport of absorbed solutes. By the action of
Difusão pela membrana (permease) de Lactose
Transporte AtivoDifusão pela membrana (permease)
de Lactose
lactose
658 Chapter 1 1: Membrane Transport of Small Molecules and the Electrical Properties of Membranes
(A)
Figure 1 1 -10 The molecular mechanismofthe bacterial lactose permeasesuggested from its crystal structure.(A) The 12 transmembrane hel ices of thepermease are clustered into two lobes,shown in two shades of green. The loopsthat connect the hel ices on either side ofthe membrane are omitted for clari ty.During transport, the hel ices sl ide and t i l tin the membrane, exposing binding sitesfor the disaccharide lactose (yellow) andH+ to either side of the membrane. (B) Inone conformational state, the H+- andlactose-binding sites are accessible to theextracellular space (top row); in the other,they are exposed to the cytosol (bottomrow). Loading the solutes on theextracel lular side is favored becausearginine (R) 144 forms a bond withglutamic acid (E) 126, leaving E269 free toaccept H+. Unloading the solutes on thecytosolic side is favored because R1 44forms a bond with E269, whichdestabi l izes the bound H+. In addit ion,the lactose-binding site is part ial lydisrupted due to the rearrangement ofthe hel ices. Because the transit ionbetween the two protonated states(middle) is forbidden, H+ can only betransported when a lactose is alsotransported. In this way, theelectrochemical H+ gradient driveslactose import. (Adapted fromJ. Abramson et al. ,Sclence 301:610-615, 2003. With permission fromAAAS.)
lactose
144A
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FORBIDDENTRANSITION
E 1
An Asymmetric Distribution of Transporters in EpithelialcellsUnderlies the Transcellular Transport of SolutesIn epithelial cells, such as those that absorb nutrients from the gut, trans-porters are distributed n_onuniformly in the plasma membrane and therebycontribute to the transcellular transport of absorbed solutes. By the action of
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659
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✴ Na+ powered glucose symport✴ Na+ pumps mantêm baixas concentrações
Enzimas
74 Chapter 2: Cell Chemistry and Biosynthesis
' i .
lake wi thWAVES
uncata yzed react ion-waves not argeenough t o su rmoun t ba r r l e r(A)
dry o(o &l) n$,
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Figure2-46 Floating ball analogies forenzyme catalysis. <TAAA> (A) A barrierdam is lowered to represent enzymecatalysis. The green ball represents apotential reactant (compound Y) that isbouncing up and down in energy leveldue to constant encounters with waves(an analogy for the thermalbombardment of the reactant moleculewith the surrounding water molecules).When the barrier (act ivat ion energy) islowered signif icantly, i t al lows theenergetical ly favorable movement of theball ( the reactant) downhil l . (B) The fourwalls of the box reoresent the activationenergy barriers for four dif ferent chemicalreactions that are al l energetical lyfavorable, in the sense that the productsare at lower energy levels than thereactants. ln the left-hand box, none ofthese reactions occurs because even thelargest waves are not large enough tosurmount any of the energy barriers. Inthe right-hand box, enzyme catalysislowers the activation energy for reactionnumber 1 only; now the jost l ing of thewaves al lows passage ofthe reactantmolecule over this energy banier,inducing reaction 1. (C) A branching r iverwith a set of barrier dams (yellow boxes)serves to i l lustrate how a series ofenzyme-catalyzed reactions determinesthe exact reaction pathway followed byeach molecule inside the cel l .
Figure 2-47 How enzymes work. Eachenzyme has an active site to which oneor more substrote molecules bind,forming an enzyme-substrate complex.A reaction occurs at the active site,producing an enzyme-product complex.fhe product is then released, al lowing theenzyme to bind further substratem n l a r r r l a <
(*- .U
catalyzed reaction-waves often surmount barrier
tt
)2̂I
aco
uncata lyzed(B )
enzyme catalys isof react ion 1
How Enzymes Find Their Substrates: The Enormous Rapidityof Molecular MotionsAn enzyme will often catalyze the reaction of thousands of substrate moleculesevery second. This means that it must be able to bind a new substrate moleculein a fraction of a millisecond. But both enzl'rnes and their substrates are presentin relatively small numbers in a cell. How do they find each other so fast? Rapidbinding is possible because the motions caused by heat energy are enormouslyfast at the molecular level. These molecular motions can be classified broadlyinto three kinds: (1) the movement of a molecule from one place to another(translational motion), (2) the rapid back-and-forth movement of covalentlylinked atoms with respect to one another (vibrations), and (3) rotations. All ofthese motions help to bring the surfaces of interacting molecules together.
The rates of molecular motions can be measured by a variety of spectro-scopic techniques. A large globular protein is constantly tumbling, rotating aboutits axis about a million times per second. Molecules are also in constant transla-tional motion, which causes them to explore the space inside the cell very effi-ciently by wandering through it-a process called diffusion. In this way, everymolecule in a cell collides with a huge number of other molecules each second.As the molecules in a liquid collide and bounce off one another, an individualmolecule moves first one way and then another, its path constituting a randomwalk (Figure 2-48). In such a walk, the average net distance that each moleculetravels (as the crow flies) from its starting point is proportional to the square rootof the time involved: that is, if it takes a molecule I second on average to travel1 pm, it takes 4 seconds to travel 2 pm, 100 seconds to travel 10 pm, and so on.
The inside of a cell is very crowded (Figure 2-49). Nevertheless, experimentsin which fluorescent dyes and other labeled molecules are injected into cells
active site
molecule A(substrate)
enzyme-su bstratecomolex
enzyme-productcomolex
molecu le B(product)
Metabolismo
Enzimas78 chapter 2: cell chemistry and Biosynthesis
X Y
UNCATALYZED REACTION
X Y
E NZYME-CATALYZED REACTION
Figure 2-53 Enzymes cannot changethe equil ibr ium point for reactions,Enzymes, l ike al l catalysts, speed up theforward and backward rates of a reactionby the same factor. Therefore, for boththe catalyzed and the uncatalyzedreactions shown here, the number ofmolecules undergoing the transit ionX -+ Y is eoual to the number ofmolecules undergoing the transit ionY -+ X when the rat io of Y molecules to Xmolecules is 3.5 to 1. In other words, thetwo reactions reach eouil ibr ium atexactly the same point.
Figure 2-54 How an energetical lyunfavorable reaction can be driven by asecond, following reaction. (A) Atequil ibr ium, there are twice as manyX molecules as Y molecules, because X isof lower energy than Y. (B) At equi l ibr ium,there are 25 t imes more Z molecules thanY molecules, because Z is of much lowerenergy than Y. (C) l f the reactions in (A)and (B) are coupled, nearly al l of the Xmolecules wil l be converted to Zmolecules. as shown.
several of the reactions in the long pathway that converts sugars into CO2 andH2O would be energetically unfavorable if considered on their or,rm. But thepathway nevertheless proceeds because the total AG for the series of sequentialreactions has a large negative value.
But forming a sequential pathway is not adequate for many purposes. Oftenthe desired pathway is simply X -+ Y without further conversion of Y to someother product. Fortunately, there are other more general ways of using enzymesto couple reactions together. How these work is the topic we discuss next.
Activated Carrier Molecules Are Essential for BiosynthesisThe energy released by the oxidation of food molecules must be stored tem-porarily before it can be channeled into the construction of the many othermolecules needed by the cell. In most cases, the energy is stored as chemicalbond energy in a small set of activated "carrier molecules," which contain one ormore energy-rich covalent bonds. These molecules diffuse rapidly throughoutthe cell and thereby carry their bond energy from sites of energy generation to thesites where energy is used for bioslnthesis and other cell activities (Figure 2-55).
The activated carriers store energy in an easily exchangeable form, either asa readily transferable chemical group or as high-energy electrons, and they canserve a dual role as a source of both energy and chemical groups in biosyntheticreactions. For historical reasons, these molecules are also sometimes referred toas coenzymes. The most important of the activated carrier molecules are ATPand two molecules that are closely related to each other, NADH and NADPH-as we discuss in detail shortly. We shall see that cells use activated carriermolecules like money to pay for reactions that otherwise could not take place.
equi l ibr ium point forX*Y react ion alone
<- --X
zequi l ibr ium point forY*Z reaction alone
zequi l ibr ium point for sequent ia l react ions X +Y +Z
(c)
Enzimas66 Chapter 2: Cell Chemistry and Biosynthesis
o t e c u le molecule molecule molecule morecure motecute ABBREVIATED A5o -o -o -a -a -o-
catalys is byenzyme 1 enzyme 2 enzyme 3 enzyme 4 enzyme 5
Figure 2-34 How a set ofenzyme-catalyzed reactions generates a metabolic pathway. Each enzymecatalyzes a part icular chemical reaction, leaving the enzyme unchanged. In this example, a set of enzymesacting in series converts molecule A to molecule F, forming a metabolic pathway.
Cell Metabolism ls Organized by EnzymesThe chemical reactions that a cell carries out would normally occur only atmuch higher temperatures than those existing inside cells. For this reason, eachreaction requires a specific boost in chemical reactivity. This requirement is cru-cial, because it allows the cell to control each reaction. The control is exertedthrough the specialized proteins called enzymes, each of which accelerates, orcatalyzes, just one of the many possible kinds of reactions that a particularmolecule might undergo. Enzyme-catalyzed reactions are usually connected inseries, so that the product of one reaction becomes the starting material, or sub-strate, for the next (Figure 2-34). These long linear reaction pathways are in turnlinked to one another, forming a maze of interconnected reactions that enablethe cell to survive, grow, and reproduce (Figure 2-35).
TWo opposing streams of chemical reactions occur in cells: (l) Ihe catabolicpathways break down foodstuffs into smaller molecules, thereby generatingboth a useful form of energy for the cell and some of the small molecules that thecell needs as building blocks, and (2) the anabolic, or biosynthellq pathways usethe energy harnessed by catabolism to drive the synthesis of the many othermolecules that form the cell. Together these two sets of reactions constitute themetabolism of the cell (Figure 2-36).
Many of the details of cell metabolism form the traditional subject of bio-chemistry and need not concern us here. But the general principles by whichcells obtain energy from their environment and use it to create order are centralto cell biology. We begin with a discussion of why a constant input of energy isneeded to sustain l iving organisms.
Biological Order ls Made Possible by the Release of Heat Energyfrom CellsThe universal tendency of things to become disordered is a fundamental law ofphysics-the second law of thermodynamics-which states that in the universe,or in any isolated system (a collection of matter that is completely isolated fromthe rest of the universe), the degree of disorder only increases. This law has suchprofound implications for all living things that we restate it in several ways.
For example, we can present the second law in terms of probability and statethat systems will change spontaneously toward those arrangements that havethe greatest probability. If we consider, for example, a box of 100 coins all lyingheads up, a series of accidents that disturbs the box will tend to move thearrangement toward a mixture of 50 heads and 50 tails. The reason is simple:there is a huge number of possible arrangements of the individual coins in themixture that can achieve the 50-50 result, but only one possible arrangementthat keeps all of the coins oriented heads up. Because the 50-50 mixture is there-fore the most probable, we say that it is more "disordered." For the same reason,
Figure 2-35 Some of the metabolic pathways and their interconnectionsin a typical cel l , About 500 common metabolic reactions are showndiagrammatical ly, with each molecule in a metabolic pathway representedby a f i l led circle, as in the yel/ow box in Figure 2-34. The pathway that ishighl ighted in this diagram with larger circles and connecting l ines is thecentral pathway of sugar metabolism, which wil l be discussed short ly.
66C
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h re
actio
n. T
he c
ontro
l is
exer
ted
thro
ugh
the
spec
ializ
ed pr
otei
ns c
alle
d en
zym
es, e
ach
of w
hich
acc
eler
ates
, or
cata
lyze
s, ju
st o
ne o
f th
e m
any
poss
ible
kin
ds o
f re
actio
ns th
at a
par
ticul
arm
olec
ule
mig
ht u
nder
go. E
nzym
e-ca
taly
zed r
eact
ions
are
usu
ally
con
nect
ed in
serie
s, so
that
the
prod
uct o
f one
reac
tion
beco
mes
the
star
ting
mat
eria
l, or
sub
-st
rate
, for t
he n
ext (
Figu
re 2-
34).
Thes
e lon
g lin
ear r
eact
ion
path
way
s are
in tu
rnlin
ked
to o
ne a
noth
er, f
orm
ing
a m
aze
of in
terc
onne
cted
reac
tions
that
ena
ble
the
cell t
o su
rviv
e, gr
ow, a
nd re
prod
uce
(Fig
ure
2-35
).TW
o opp
osin
g st
ream
s of c
hem
ical
reac
tions
occu
r in
cells
: (l)
Ihe
cata
bolic
path
way
s br
eak
dow
n fo
odst
uffs
into
sm
alle
r m
olec
ules
, the
reby
gen
erat
ing
both
a u
sefu
l form
of e
nerg
y for
the
cell a
nd s
ome o
f the
sm
all m
olec
ules
that
the
cell n
eeds
as bu
ildin
g bl
ocks
, and
(2) t
he a
nabo
lic, o
r bio
synt
hellq
pat
hway
s use
the
ener
gy h
arne
ssed
by c
atab
olis
m to
driv
e th
e sy
nthe
sis o
f the
man
y ot
her
mol
ecul
es th
at fo
rm th
e ce
ll. T
oget
her t
hese
two
sets
of re
actio
ns co
nstit
ute
the
met
abol
ism
of t
he c
ell (
Figu
re 2
-36)
.M
any
of th
e de
tails
of c
ell m
etab
olis
m fo
rm t
he tr
aditi
onal
sub
ject
of b
io-
chem
istry
and
need
not
con
cern
us
here
. But
the
gene
ral p
rinci
ples
by
whi
chce
lls ob
tain
ene
rgy f
rom
thei
r env
ironm
ent a
nd u
se it
to c
reat
e ord
er a
re ce
ntra
lto
cel
l bio
logy
. We
begi
n w
ith a
dis
cuss
ion
of w
hy a
con
stan
t inp
ut o
f ene
rgy i
sne
eded
to s
usta
in liv
ing
orga
nism
s.
Bio
logi
cal Ord
er ls
Mad
e Pos
sibl
e by th
e Rel
ease
of
Hea
t Ene
rgy
from
Cel
lsTh
e un
iver
sal t
ende
ncy
of th
ings
to b
ecom
e di
sord
ered
is a
fund
amen
tal l
aw o
fph
ysic
s-th
e se
cond
law
of t
herm
odyn
amic
s-w
hich
st
ates
that
in th
e un
iver
se,
or in
any
isol
ated
syst
em (a
colle
ctio
n of
mat
ter t
hat i
s co
mpl
etel
y is
olat
ed fr
omth
e re
st of
the
univ
erse
), the
deg
ree o
f dis
orde
r onl
y in
crea
ses.
This
law
has
such
prof
ound
impl
icat
ions
for a
ll liv
ing
thin
gs th
at w
e re
stat
e it i
n se
vera
l way
s.Fo
r exa
mpl
e, w
e ca
n pre
sent
the
seco
nd la
w in
term
s of
pro
babi
lity
and
stat
eth
at s
yste
ms w
ill c
hang
e sp
onta
neou
sly t
owar
d th
ose
arra
ngem
ents
that
hav
eth
e gr
eate
st pr
obab
ility
. If w
e co
nsid
er, fo
r exa
mpl
e, a
box
of 1
00 co
ins
all l
ying
head
s up
, a
serie
s of
acc
iden
ts th
at d
istu
rbs
the
box
will
ten
d to
mov
e th
ear
rang
emen
t tow
ard
a m
ixtu
re o
f 50
head
s an
d 50
tails
. The
reas
on is
sim
ple:
ther
e is
a h
uge
num
ber
of p
ossi
ble
arra
ngem
ents
of th
e in
divi
dual
coi
ns in
the
mix
ture
that
can
ach
ieve
the
50-5
0 re
sult,
but
onl
y on
e po
ssib
le a
rran
gem
ent
that
kee
ps al
l of t
he c
oins
orie
nted
hea
ds up
. Bec
ause
the
50-5
0 m
ixtu
re is
ther
e-fo
re th
e m
ost p
roba
ble,
we
say t
hat i
t is m
ore
"dis
orde
red.
" For
the
sam
e rea
son,
Figu
re 2-
35 S
ome o
f the
met
abol
ic pa
thw
ays a
nd th
eir i
nter
conn
ectio
nsin
a ty
pica
l cel
l, Abo
ut 50
0 com
mon
met
abol
ic re
actio
ns are s
how
ndi
agra
mm
atic
ally
, w
ith ea
ch m
olec
ule in
a m
etab
olic
path
way
repr
esen
ted
by a
fille
d circ
le, as
in th
e yel
/ow
box i
n Fi
gure
2-34
. The
path
way
that
ishi
ghlig
hted
in th
is di
agra
m with
larg
er ci
rcle
s and
conn
ectin
g line
s is th
ece
ntra
l path
way
of su
gar m
etab
olis
m, whi
ch w
ill be
disc
usse
d shor
tly.
66 Chapter 2: Cell Chemistry and Biosynthesis
o t e c u le molecule molecule molecule morecure motecute ABBREVIATED A5o -o -o -a -a -o-
catalys is byenzyme 1 enzyme 2 enzyme 3 enzyme 4 enzyme 5
Figure 2-34 How a set ofenzyme-catalyzed reactions generates a metabolic pathway. Each enzymecatalyzes a part icular chemical reaction, leaving the enzyme unchanged. In this example, a set of enzymesacting in series converts molecule A to molecule F, forming a metabolic pathway.
Cell Metabolism ls Organized by EnzymesThe chemical reactions that a cell carries out would normally occur only atmuch higher temperatures than those existing inside cells. For this reason, eachreaction requires a specific boost in chemical reactivity. This requirement is cru-cial, because it allows the cell to control each reaction. The control is exertedthrough the specialized proteins called enzymes, each of which accelerates, orcatalyzes, just one of the many possible kinds of reactions that a particularmolecule might undergo. Enzyme-catalyzed reactions are usually connected inseries, so that the product of one reaction becomes the starting material, or sub-strate, for the next (Figure 2-34). These long linear reaction pathways are in turnlinked to one another, forming a maze of interconnected reactions that enablethe cell to survive, grow, and reproduce (Figure 2-35).
TWo opposing streams of chemical reactions occur in cells: (l) Ihe catabolicpathways break down foodstuffs into smaller molecules, thereby generatingboth a useful form of energy for the cell and some of the small molecules that thecell needs as building blocks, and (2) the anabolic, or biosynthellq pathways usethe energy harnessed by catabolism to drive the synthesis of the many othermolecules that form the cell. Together these two sets of reactions constitute themetabolism of the cell (Figure 2-36).
Many of the details of cell metabolism form the traditional subject of bio-chemistry and need not concern us here. But the general principles by whichcells obtain energy from their environment and use it to create order are centralto cell biology. We begin with a discussion of why a constant input of energy isneeded to sustain l iving organisms.
Biological Order ls Made Possible by the Release of Heat Energyfrom CellsThe universal tendency of things to become disordered is a fundamental law ofphysics-the second law of thermodynamics-which states that in the universe,or in any isolated system (a collection of matter that is completely isolated fromthe rest of the universe), the degree of disorder only increases. This law has suchprofound implications for all living things that we restate it in several ways.
For example, we can present the second law in terms of probability and statethat systems will change spontaneously toward those arrangements that havethe greatest probability. If we consider, for example, a box of 100 coins all lyingheads up, a series of accidents that disturbs the box will tend to move thearrangement toward a mixture of 50 heads and 50 tails. The reason is simple:there is a huge number of possible arrangements of the individual coins in themixture that can achieve the 50-50 result, but only one possible arrangementthat keeps all of the coins oriented heads up. Because the 50-50 mixture is there-fore the most probable, we say that it is more "disordered." For the same reason,
Figure 2-35 Some of the metabolic pathways and their interconnectionsin a typical cel l , About 500 common metabolic reactions are showndiagrammatical ly, with each molecule in a metabolic pathway representedby a f i l led circle, as in the yel/ow box in Figure 2-34. The pathway that ishighl ighted in this diagram with larger circles and connecting l ines is thecentral pathway of sugar metabolism, which wil l be discussed short ly.
Alguns caminhos metabólicos de uma
célula típica
Enzimas10
2C
hapt
er 2: C
ell C
hem
istr
y and B
iosy
nthe
sis
thes
e pr
oces
ses r
equi
red
in d
iffer
ent
tissu
es a
re n
ot t
he s
ame.
For
exa
mpl
e,ne
rve
cells
, whi
ch a
re p
roba
bly
the
mos
t fas
tidio
us c
ells
in th
e bo
dy, m
aint
ain
alm
ost n
o re
serv
es of
gly
coge
n or f
atty
aci
ds a
nd re
ly a
lmos
t ent
irely
on
a co
n-st
ant s
uppl
y of
glu
cose
from
the
bloo
dstre
am. I
n co
ntra
st, li
ver c
ells
supp
ly g
lu-
cose
to a
ctiv
ely c
ontra
ctin
g m
uscl
e ce
lls an
d re
cycl
e the
lact
ic a
cid
prod
uced
by
mus
cle
cells
back
into
glu
cose
. All
type
s of c
ells
have
thei
r dis
tinct
ive
met
abol
ictra
its, a
nd th
ey c
oope
rate
exte
nsiv
ely i
n th
e no
rmal
sta
te, a
s wel
l as i
n re
spon
seto
stre
ss an
d st
arva
tion.
One
mig
ht th
ink
that
the
who
le s
yste
m w
ould
nee
d to
be s
o fin
ely
bala
nced
that
any
min
or u
pset
, suc
h as
a te
mpo
rary
cha
nge
indi
etar
y in
take
, wou
ld b
e di
sast
rous
.In
fact
, the
met
abol
ic b
alan
ce of
a ce
ll is a
maz
ingl
y sta
ble.
\.A/h
enev
er the
bal-
ance
is p
ertu
rbed
, the
cel
l rea
cts s
o as
to r
esto
re th
e in
itial
sta
te. T
he c
ell c
anad
apt a
nd c
ontin
ue to
func
tion
durin
g st
arva
tion
or d
isea
se. M
utat
ions
of m
any
kind
s ca
n da
mag
e or e
ven e
limin
ate
parti
cula
r rea
ctio
n pat
hway
s, an
d ye
t-pro
-vi
ded
that
cer
tain
min
imum
req
uire
men
ts a
re m
et-th
e ce
ll sur
vive
s. It
does
sobe
caus
e an
elab
orat
e net
wor
k of
con
trol m
echa
nism
s reg
ulat
es an
d co
ordi
nate
sth
e ra
tes o
f all
of it
s re
actio
ns. T
hese
cont
rols
rest
, ulti
mat
ely,
on
the
rem
arka
ble
abili
ties
of p
rote
ins
to c
hang
e th
eir
shap
e an
d th
eir
chem
istry
in r
espo
nse t
och
ange
s in
thei
r im
med
iate
env
ironm
ent.
The
prin
cipl
es th
at u
nder
lie h
ow la
rge
mol
ecul
es s
uch
as pr
otei
ns a
re b
uilt
and
the
chem
istry
beh
ind
thei
r reg
ulat
ion
will
be
our n
ext c
once
rn.
Figu
re 2-
88 G
lyco
lysi
s and
the
citri
cac
id cy
cle a
re at
the
cent
er of
met
abol
ism
. Som
e 500
met
abol
icre
act io
ns of a
typi
cal ce
l l are
show
nsc
hem
atic
ally
w
ith th
e re
act io
ns of
glyc
olys
is
and t
he ci
tric
acid
cycl
e in r
ed.
Oth
er re
actio
ns eith
er le
ad in
to th
ese
two
cent
ral pa
thw
ays-
del iv
erin
g smal
lm
olec
ules
to b
e cat
abol
ized
w
ithpr
oduc
tion o
f ene
rgy-
or th
ey le
adou
twar
d and
ther
eby s
uppl
y car
bon
com
poun
ds for t
he p
urpo
se of
bios
ynth
esis
.
Mitocondria - Geradores de energia
818 Chapter 14: Energy Conversion: Mitochondria and Chloroplasts
Matrix. This large internal space contains a highly concentratedmixture of hundreds of enzymes, including those required for theoxidation of pyruvate and fatty acids and for the citr ic acid cycle. Thematrix also contains several identical copies of the mitochondrial DNAgenome, special mitochondrial r ibosomes, tRNAs, and various enzymesrequired for expression of the mitochondrial genes.Inner membrane. The inner membrane is folded into numerous crrstae.
charged molecu les .Outer membrane. Because i t contains a large channel-forming protein(a porin, VDAC), the outer membrane is permeable to al l molecules of5000 da l tons or less . Other p ro te ins in t f r i s membrane inc lude enzymesinvo lved in mi tochondr ia l l i p id syn thes is and enzymes tha t conve i tl ipid substrates into forms that are subsequently metabolized in thematrix, import receptors for mitochondrial proteins, and enzymaticmach inery fo r d iv is ion and fus ion o f the organe l le .Intermembrane space. This space contains several enzymes that usethe ATP passing out of the matrix to phosphorylate ofher nucleotides.
rob nfrFigure 1 4-8 The structure of amitochondrion. <CGAT> In the l iver, anestimated 670lo of the totalmitochondrial protein is located in thematrix,2lo/o is located in the lnnermembrane,60lo in the outer membrane,and 60/o in the intermembrane soace. Asindicated below, each of these fourregions contains a special set of proteinsthat mediate dist inct functions. (Largemicrograph courtesy of Daniel S. Friend;small micrograph and three-dimensionalreconstruction from T.G. Frey,C.W. Renken and G.A. Perkins, Biochim.Biophys. Acta 1555:196-203, 2002. Withpermission from Elsevier.)300
" t
consumed. Nearly all the energy available from burning carbohydrates, fats, andother foodstuffs in the earlier stages of their oxidation is initially saved in theform of high-energy electrons removed from substrates by NAD+ and FAD. Theseelectrons, carried by NADH and FADH2, then combine with 02 by means of the
two electrons to electron-+ Transport chatn In membrane
Figure 14-9 How NADH donates electrons. In this diagram, the high-energy electrons are shown as two reddots on ayel lowhydrogen atom. A hydride ion (H-, a hydrogen atom with an extra electron) is removed from NADH and is convertedinto a proton and two high-energy electrons: H- -+ H+ + 2e-. Only the r ing that carr ies the electrons in a high-energyl inkage is shown; for the complete structure and the conversion of NAD+ back to NADH, see the structure of the closelyrelated NADPH in Figure 2-60. Electrons are also carr ied in a similar way by FADH2, whose structure is shown in Figure 2-83.
ELECTRONDONATION-T*
I+ide i on H :
t\
H ' 2 e -
two high-energyelectrons f romsugar oxidat ion
o- ' - N H ,
H
hydr
unstable isomer
H O
" l l' c t c ' c - N H ,I t l
n - t - f - t - nI
BONDREARRANGEMENT
n o
I
66 Chapter 2: Cell Chemistry and Biosynthesis
o t e c u le molecule molecule molecule morecure motecute ABBREVIATED A5o -o -o -a -a -o-
catalys is byenzyme 1 enzyme 2 enzyme 3 enzyme 4 enzyme 5
Figure 2-34 How a set ofenzyme-catalyzed reactions generates a metabolic pathway. Each enzymecatalyzes a part icular chemical reaction, leaving the enzyme unchanged. In this example, a set of enzymesacting in series converts molecule A to molecule F, forming a metabolic pathway.
Cell Metabolism ls Organized by EnzymesThe chemical reactions that a cell carries out would normally occur only atmuch higher temperatures than those existing inside cells. For this reason, eachreaction requires a specific boost in chemical reactivity. This requirement is cru-cial, because it allows the cell to control each reaction. The control is exertedthrough the specialized proteins called enzymes, each of which accelerates, orcatalyzes, just one of the many possible kinds of reactions that a particularmolecule might undergo. Enzyme-catalyzed reactions are usually connected inseries, so that the product of one reaction becomes the starting material, or sub-strate, for the next (Figure 2-34). These long linear reaction pathways are in turnlinked to one another, forming a maze of interconnected reactions that enablethe cell to survive, grow, and reproduce (Figure 2-35).
TWo opposing streams of chemical reactions occur in cells: (l) Ihe catabolicpathways break down foodstuffs into smaller molecules, thereby generatingboth a useful form of energy for the cell and some of the small molecules that thecell needs as building blocks, and (2) the anabolic, or biosynthellq pathways usethe energy harnessed by catabolism to drive the synthesis of the many othermolecules that form the cell. Together these two sets of reactions constitute themetabolism of the cell (Figure 2-36).
Many of the details of cell metabolism form the traditional subject of bio-chemistry and need not concern us here. But the general principles by whichcells obtain energy from their environment and use it to create order are centralto cell biology. We begin with a discussion of why a constant input of energy isneeded to sustain l iving organisms.
Biological Order ls Made Possible by the Release of Heat Energyfrom CellsThe universal tendency of things to become disordered is a fundamental law ofphysics-the second law of thermodynamics-which states that in the universe,or in any isolated system (a collection of matter that is completely isolated fromthe rest of the universe), the degree of disorder only increases. This law has suchprofound implications for all living things that we restate it in several ways.
For example, we can present the second law in terms of probability and statethat systems will change spontaneously toward those arrangements that havethe greatest probability. If we consider, for example, a box of 100 coins all lyingheads up, a series of accidents that disturbs the box will tend to move thearrangement toward a mixture of 50 heads and 50 tails. The reason is simple:there is a huge number of possible arrangements of the individual coins in themixture that can achieve the 50-50 result, but only one possible arrangementthat keeps all of the coins oriented heads up. Because the 50-50 mixture is there-fore the most probable, we say that it is more "disordered." For the same reason,
Figure 2-35 Some of the metabolic pathways and their interconnectionsin a typical cel l , About 500 common metabolic reactions are showndiagrammatical ly, with each molecule in a metabolic pathway representedby a f i l led circle, as in the yel/ow box in Figure 2-34. The pathway that ishighl ighted in this diagram with larger circles and connecting l ines is thecentral pathway of sugar metabolism, which wil l be discussed short ly.
Mitocondria - Geradores de energia
818 Chapter 14: Energy Conversion: Mitochondria and Chloroplasts
Matrix. This large internal space contains a highly concentratedmixture of hundreds of enzymes, including those required for theoxidation of pyruvate and fatty acids and for the citr ic acid cycle. Thematrix also contains several identical copies of the mitochondrial DNAgenome, special mitochondrial r ibosomes, tRNAs, and various enzymesrequired for expression of the mitochondrial genes.Inner membrane. The inner membrane is folded into numerous crrstae.
charged molecu les .Outer membrane. Because i t contains a large channel-forming protein(a porin, VDAC), the outer membrane is permeable to al l molecules of5000 da l tons or less . Other p ro te ins in t f r i s membrane inc lude enzymesinvo lved in mi tochondr ia l l i p id syn thes is and enzymes tha t conve i tl ipid substrates into forms that are subsequently metabolized in thematrix, import receptors for mitochondrial proteins, and enzymaticmach inery fo r d iv is ion and fus ion o f the organe l le .Intermembrane space. This space contains several enzymes that usethe ATP passing out of the matrix to phosphorylate ofher nucleotides.
rob nfrFigure 1 4-8 The structure of amitochondrion. <CGAT> In the l iver, anestimated 670lo of the totalmitochondrial protein is located in thematrix,2lo/o is located in the lnnermembrane,60lo in the outer membrane,and 60/o in the intermembrane soace. Asindicated below, each of these fourregions contains a special set of proteinsthat mediate dist inct functions. (Largemicrograph courtesy of Daniel S. Friend;small micrograph and three-dimensionalreconstruction from T.G. Frey,C.W. Renken and G.A. Perkins, Biochim.Biophys. Acta 1555:196-203, 2002. Withpermission from Elsevier.)300
" t
consumed. Nearly all the energy available from burning carbohydrates, fats, andother foodstuffs in the earlier stages of their oxidation is initially saved in theform of high-energy electrons removed from substrates by NAD+ and FAD. Theseelectrons, carried by NADH and FADH2, then combine with 02 by means of the
two electrons to electron-+ Transport chatn In membrane
Figure 14-9 How NADH donates electrons. In this diagram, the high-energy electrons are shown as two reddots on ayel lowhydrogen atom. A hydride ion (H-, a hydrogen atom with an extra electron) is removed from NADH and is convertedinto a proton and two high-energy electrons: H- -+ H+ + 2e-. Only the r ing that carr ies the electrons in a high-energyl inkage is shown; for the complete structure and the conversion of NAD+ back to NADH, see the structure of the closelyrelated NADPH in Figure 2-60. Electrons are also carr ied in a similar way by FADH2, whose structure is shown in Figure 2-83.
ELECTRONDONATION-T*
I+ide i on H :
t\
H ' 2 e -
two high-energyelectrons f romsugar oxidat ion
o- ' - N H ,
H
hydr
unstable isomer
H O
" l l' c t c ' c - N H ,I t l
n - t - f - t - nI
BONDREARRANGEMENT
n o
I
66 Chapter 2: Cell Chemistry and Biosynthesis
o t e c u le molecule molecule molecule morecure motecute ABBREVIATED A5o -o -o -a -a -o-
catalys is byenzyme 1 enzyme 2 enzyme 3 enzyme 4 enzyme 5
Figure 2-34 How a set ofenzyme-catalyzed reactions generates a metabolic pathway. Each enzymecatalyzes a part icular chemical reaction, leaving the enzyme unchanged. In this example, a set of enzymesacting in series converts molecule A to molecule F, forming a metabolic pathway.
Cell Metabolism ls Organized by EnzymesThe chemical reactions that a cell carries out would normally occur only atmuch higher temperatures than those existing inside cells. For this reason, eachreaction requires a specific boost in chemical reactivity. This requirement is cru-cial, because it allows the cell to control each reaction. The control is exertedthrough the specialized proteins called enzymes, each of which accelerates, orcatalyzes, just one of the many possible kinds of reactions that a particularmolecule might undergo. Enzyme-catalyzed reactions are usually connected inseries, so that the product of one reaction becomes the starting material, or sub-strate, for the next (Figure 2-34). These long linear reaction pathways are in turnlinked to one another, forming a maze of interconnected reactions that enablethe cell to survive, grow, and reproduce (Figure 2-35).
TWo opposing streams of chemical reactions occur in cells: (l) Ihe catabolicpathways break down foodstuffs into smaller molecules, thereby generatingboth a useful form of energy for the cell and some of the small molecules that thecell needs as building blocks, and (2) the anabolic, or biosynthellq pathways usethe energy harnessed by catabolism to drive the synthesis of the many othermolecules that form the cell. Together these two sets of reactions constitute themetabolism of the cell (Figure 2-36).
Many of the details of cell metabolism form the traditional subject of bio-chemistry and need not concern us here. But the general principles by whichcells obtain energy from their environment and use it to create order are centralto cell biology. We begin with a discussion of why a constant input of energy isneeded to sustain l iving organisms.
Biological Order ls Made Possible by the Release of Heat Energyfrom CellsThe universal tendency of things to become disordered is a fundamental law ofphysics-the second law of thermodynamics-which states that in the universe,or in any isolated system (a collection of matter that is completely isolated fromthe rest of the universe), the degree of disorder only increases. This law has suchprofound implications for all living things that we restate it in several ways.
For example, we can present the second law in terms of probability and statethat systems will change spontaneously toward those arrangements that havethe greatest probability. If we consider, for example, a box of 100 coins all lyingheads up, a series of accidents that disturbs the box will tend to move thearrangement toward a mixture of 50 heads and 50 tails. The reason is simple:there is a huge number of possible arrangements of the individual coins in themixture that can achieve the 50-50 result, but only one possible arrangementthat keeps all of the coins oriented heads up. Because the 50-50 mixture is there-fore the most probable, we say that it is more "disordered." For the same reason,
Figure 2-35 Some of the metabolic pathways and their interconnectionsin a typical cel l , About 500 common metabolic reactions are showndiagrammatical ly, with each molecule in a metabolic pathway representedby a f i l led circle, as in the yel/ow box in Figure 2-34. The pathway that ishighl ighted in this diagram with larger circles and connecting l ines is thecentral pathway of sugar metabolism, which wil l be discussed short ly.
Mitocondria - Geradores de energia
1.Mitocondria são organelas atípicas2.São nosso gerador de energia3.Elas se duplicam independentemente das células
que residem (seres unicelulares procarionte) 4.Acredita-se que houve uma simbiose em um
passado remoto. Nesse caso, a célula invasora se protege dentro da hospedeira que passa a contar com uma fonte de energia
http://www.nature.com/scitable/topicpage/mitochondria-14053590Capitulo 14 do Livro de Molecular Biology, Alberts
Mitocondria - Geradores de energia
Membrana externaMembrana interna
Cristas
grandes poros de proteínas (permite a passagem de íons e moléculas grandes)
* menos poroso, mais próximo a membrana plasmática* proteínas para transporte de elétrons e síntese de ATP
Mitocondria - Geradores de energia
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Mitocondria - Geradores de energia
88 Chapter 2: Cell Chemistry and Biosynthesis
HOW CELLS OBTAIN ENERGY FROM FOODThe constant supply of energy that cells need to generate and maintain the bio-logical order that keeps them alive comes from the chemical bond energy infood molecules, which thereby serve as fuel for cells.
The proteins, lipids, and polysaccharides that make up most of the food weeat must be broken down into smaller molecules before our cells can use them-either as a source of energy or as building blocks for other molecules. EnzFnaticdigestion breaks down the large polymeric molecules in food into theirmonomer subunits-proteins into amino acids, polysaccharides into sugars,and fats into fatty acids and glycerol. After d^igestion, the small orginicmolecules derived from food enter the cltosol of cells, where their gradual oxi-dation begins.
Sugars are particularly important fuel molecules, and they are oxidized insmall controlled steps to carbon dioxide (coz) and water (Figure 2-69). In thissection we trace the major steps in the breakdor.tm, or catabolism, of sugars andshow how they produce ATB NADH, and other activated carrier molecules inanimal cells. A very similar pathway also operates in plants, fungi, and manybacteria. As we shall see, the oxidation of fatty acids is equally important forcells. other molecules, such as proteins, can also serve as energy sources whenthey are funneled through appropriate enzymatic pathways.
Glycolysis ls a Central ATP-Producing PathwayThe major process for oxidizing sugars is the sequence of reactions known as
verted into two molecules of pyruuate, each of which contains three carbonatoms. For each glucose molecule, two molecules of ATp are hydrolyzed to pro-vide energy to drive the early steps, but four molecules of Arp are produced inthe later steps. At the end of glycolysis, there is consequently a nef gain of twomolecules of AIP for each glucose molecule broken down.
The glycolltic pathway is outlined in Figure 2-zo and shown in more detailin Panel 2-8 (pp. I?}-IZL). Glycolysis involves a sequence of l0 separate reac_tions, each producing a different sugar intermediate and each caialvzed bv a
(A) stepwise oxidation of sugar in cells (B) d i rect burning of sugar
smal l act ivat ion energiesovercome at bodytemperature owing to thepresence of enzymes
SUGAR + O,IaqoE
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al l f reeenergy rsreteaSedas heat;none rsstored
Figure 2-69 Schematic representationof the controlled stepwise oxidation ofsugar in a cel l , compared with ordinaryburning, (A) In the cel l , enzymes catalyzeoxidation via a series of small steos inwhich free energy is transferred inconveniently sized packets to carr iermolecules-most often ATP and NADH.At each step, an enzyme controls thereaction by reducing the activationenergy barrier that has to be surmountedbefore the specific reaction can occur.The total free energy released is exactlythe same in (A) and (B). But i f the sugarwere instead oxidized to CO2 and H2O ina single step, as in (B), i t would release anamount of energy much larger thancould be captured for useful purposes.
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Mitocondria - Geradores de energia
98 Chapter 2: Cell Chemistry and Biosynthesis
eventually focused on the oxidation ofpyruvate and led in 1937 to the discoveryof the citric acid cycle, also knoum as the tricarboxylic acid cycle or the Krebscycle.The citric acid cycle accounts for about two-thirds of the total oxidation ofcarbon compounds in most cells, and its major end products are CO2 and high-energy electrons in the form of NADH. The CO2 is released as a waste product,while the high-energy electrons from NADH are passed to a membrane-boundelectron-transport chain (discussed in Chapter 14), eventually combining with02 to produce H2O. Although the citric acid cycle itself does not use 02, itrequires 02 in order to proceed because there is no other efficient way for theNADH to get rid of its electrons and thus regenerate the NAD+ that is needed tokeep the cycle going.
The citric acid cycle takes place inside mitochondria in eucaryotic cells. Itresults in the complete oxidation of the carbon atoms of the acetyl groups inacetyl CoA, converting them into CO2. But the acetyl group is not oxidizeddirectly. Instead, this group is transferred from acetyl CoA to a larger, four-car-bon molecule, oxaloacetate, to form the six-carbon tricarboxylic acid, citric acid,for which the subsequent cycle of reactions is named. The citric acid molecule isthen gradually oxidized, allowing the energy of this oxidation to be harnessed toproduce energy-rich activated carrier molecules. The chain of eight reactionsforms a cycle because at the end the oxaloacetate is regenerated and enters anew turn of the cycle, as shown in outline in Figure 2-82.
we have thus far discussed only one of the three types of activated carriermolecules that are produced by the citric acid cycle, the NAD+-NADH pair (seeFigure 2-60). In addition to three molecules of NADH, each turn of the cycle alsoproduces one molecule of FADH2 (reduced flavin adenine dinucleotide) fromFAD and one molecule of the ribonucleotide GTP (guanosine triphosphate)from GDP The structures of these two activated carrier molecules are illustratedin Figure 2-83. GTP is a close relative of ATB and the transfer of its terminalphosphate group to ADP produces one ATP molecule in each cycle. Like NADH,FADHz is a carrier of high-energy electrons and hydrogen. As we discuss shortly,the energy that is stored in the readily transferred high-energy electrons ofNADH and FADH2 will be utilized subsequently for Arp production through theprocess of oxidatiue phosphorylation, the only step in the oxidative catabolismof foodstuffs that directly requires gaseous oxygen (oz) from the atmosphere.
Panel 2-9 (pp. 122-123) presents the complete citric acid cycle. Water, ratherthan molecular oxygen, supplies the extra oxygen atoms required to make co2from the acetyl groups entering the citric acid cycle. As illustrated in the panel,
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Figure 2-82 Simple overview of thecitric acid cycle. <TAGT> The reaction ofacetyl coA with oxaloacetate starts thecycle by producing citrate (citr ic acid). Ineach turn of the cycle, two molecules ofCO2 are produced as waste products, plusthree molecules of NADH, one moleculeof GTP, and one molecule of FADH2. Thenumber of carbon atoms in eachintermediate is shown in a yellow box.For details, see Panel 2-9 (pp. 122-123).
Mitocondria - Geradores de energia100 Chapter 2: Cell Chemistry and Biosynthesis
Electron Transport Drives the Synthesis of the Majority of the ATPin Most CellsMost chemical energy is released in the last step in the degradation of a foodmolecule. In this final process the electron carriers NADH and FADH2 transferthe electrons that they have gained when oxidizing other molecules to the elec-tron-transport chain, which is embedded in the inner membrane of the mito-chondrion (see Figure 14-10). As the electrons pass along this long chain of spe-cialized electron acceptor and donor molecules, they fall to successively lowerenergy states. The energy that the electrons release in this process pumps H+ions (protons) across the membrane-from the inner mitochondrial compart-ment to the outside-generating a gradient of H+ ions (Figure 2-85). This gradi-ent serves as a source of energy, being tapped like a battery to drive a variety ofenergy-requiring reactions. The most prominent of these reactions is the gener-ation of ATP by the phosphorylation of ADP
At the end of this series of electron transfers, the electrons are passed tomolecules of oxygen gas (Oz) that have diffused into the mitochondrion, whichsimultaneously combine with protons (H*) from the surrounding solution toproduce water molecules. The electrons have now reached their lowest energyIevel, and therefore all the available energy has been extracted from the oxidizedfood molecule. This process, termed oxidative phosphorylation (Figure 2-86),also occurs in the plasma membrane of bacteria. As one of the most remarkableachievements of cell evolution, it is a central topic of Chapter 14.
In total, the complete oxidation of a molecule of glucose to H2O and CO2 isused by the cell to produce about 30 molecules of ATP In contrast, only 2molecules of ATP are produced per molecule of glucose by glycolysis alone.
Amino Acids and Nucleotides Are Part of the Nitrogen CycleSo far we have concentrated mainly on carbohydrate metabolism and have notyet considered the metabolism of nitrogen or sulfur. These two elements areimportant constituents of biological macromolecules. Nitrogen and sulfuratoms pass from compound to compound and between organisms and theirenvironment in a series of reversible cycles.
Although molecular nitrogen is abundant in the Earth's atmosphere, nitro-gen is chemically unreactive as a gas. Only a few living species are able to incor-porate it into organic molecules, a process called nitrogen fixation. Nitrogenfixation occurs in certain microorganisms and by some geophysical processes,such as lightning discharge. It is essential to the biosphere as a whole, for with-out it life could not exist on this planet. Only a small fraction of the nitrogenouscompounds in today's organisms, however, is due to fresh products of nitrogenfixation from the atmosphere. Most organic nitrogen has been in circulation for
pyruvate fromg lycolysis
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Figure 2-85 The generation of anH+ gradient across a membrane byelectron-transport reactions.A high-energy electron (derived, forexample, from the oxidation of ametaboli te) is passed sequential ly bycarriers A, B, and C to a lower energystate. In this diagram carrier B is arrangedin the membrane in such a way that i ttakes up H+ from one side and releases i tto the other as the electron passes. Theresult is an H+ gradient. As discussed inChapter 14, this gradient is an importantform of energy that is harnessed by othermembrane oroteins to drive theformation of ATP.
Figure 2-86 The f inal stages of oxidationof food molecules. Molecules of NADHand FADH2 (FADHz is not shown) areproduced by the citr ic acid cycle. Theseactivated carr iers donate high-energyelectrons that are eventual ly used toreduce oxygen gas to water.A major port ion of the energy releasedduring the transfer of these electronsalong an electron-transfer chain in themitochondrial inner membrane (or in theplasma membrane of bacteria) isharnessed to drive the synthesis of ATP-hence the name oxidativephosphorylat ion (discussed in Chapter 14).
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Mitocondria - Geradores de energia
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'Gt-Vt arnBIU)epceloruuaBdxo eqt ol suorlJala eq] Jo uoutppp purJ aqt Lq palearc saSruqc alrle-3au aql ezrleJlnau 01 pesn are,{aql uaqm'dlluaueruJad peurnlar suolord eql eJpureqc lrodsueJl-uoJlcele aql Jo pue eql ]e dpo lng 'peurquotar .,(FuersueJl aJesuoJlrale pue suolord ',{ea,r aq] Suop sdals IeJeAas lV'auerqueu IerJpuoqf,o]nuJauur eql ur sJarrJpJ uoJlf,ela Jo sarJes e q8norql ssed suoJlJele er{J 'suoJlJelepue suolord olur paleredes lsJrJ eJE sruole uaSorpr(q eql'lpeq sE luaruuoJrluaeql ol 1so1 Suraq Jo peelsur paJols aq ueJ peseeleJ.{8raua aql Jo }soru lpql os'sdals leurs dueur ur rnclo o] eperu sr OzH <- zO z/r + zH uorlJeal elqurone; dlec-lla8Jeue eqJ'erues aql sr aydrcurrd aql 'suollJpeJ orloqeleJ Jaqlo ut pesn teqlupql usruBqceu lualaJJrp e ,tq dSraua slsa^Jeq umqc drolerrdsar aql qSnoqlry
saxelduo) au/kul {ro1el ldsege6rel aerql qbnorql ua6{x9 ol suol1rell s}t sraJsuell HCVN
'JelPI JoJ urcqc ^,fuo1errd-sar aqtJo slretep aq] Supes 'alqrssod uor1e1,{roqdsoqd anrluprxo aleru }eqt suop-f,Ear Jo ad& aqr aqrJJsap Lgapq [eqs allr uollJas srqt Jo rapureuer eqt uI
'paldacce dleraua8 ]l e{eru ol pe}eFrunJJe eJuaprla Surpoddnsq8noua aloJeq srea.,i. auros sE^ ll leql Ielou os sE^ Bepr eql ,sseleqleuo111 .I8o1orqIIaJ ur alzznd Supuels-8uo1 e paureldxa ursrupqreru slq] 'I96I ur pasodord lsrgspm ]r uarl\\'ssacord Jrlotusorueqc e uo spuadep ureqo zfuolerrdsar eql erl uoll-e1,rfuoqdsoqd a,rqepxo dq alVJo uorleraua8 aql 'peuortuaur.,(lsnonard sy
'(I I-?I arnE;g) suorloeer Jo sarres lsEI slql eqrrcsap 01 pesnsr uo;1u1d;oqdsoqd e^llupTxo uJet eql 'uosear slql JoC aJV ol Id + dCV Jo uors-ra^uos eql e^rJp ol paseeleJ u{3raua Jo lunorue a3ru1 aqt sasseuJBq eueJqruetuJeuur eql'aupJqrueu lerJpuor{Jotrur Jeuur aql q peppequa ureqf, drolerrdsar
tosol^f tAour sltnflton qool
spr>e {ge; alennrld
rd + dcv
oc
uo tstanuo>-{6raua
(
*H+zoz/t * EN ozH +
'(7E-yg arn6rg osleeas) ure6e HCVN Iq pa)npar s! l! alaLlm
'1osoy{r eLll ol paurn}er sr punoduo>srrll /pazrptxo 6uraq rarye iuoupuoq)ottr!
aq] olur punoouro) pa)npal JeqloueUodsuerl leql suals{s,,elunqs,, lela^as Joauo ro supau Iq {1t>arrpur paqsr;dr.uo>te
aq lsnur p6y11 tr;osoll> uolJ laJsuerluorl)ala aql'auerquaLU leupuoqloltul
lauut aql ssorte ssed louuetHOVN a)uls'(uMoLls lou) utpLl),{tolerrdsar
eql ol suortfale sassed osle ;osoy(teqt ur srs{;or{;6 trg palereua6 HCVN aql '( 1-y 1 arn6r3 eas; aseqtu,{s dlv Iq dlv Jouorl)npold aql sa^up q)tqM ,auerqtuau
lauut aql ssolle luarpel6 uololde salereueb l.rodsuerl uotl)ala slql .(zO)ua6,(xo o1 aueiqulaul tauur aql ut uteq)
Uodsuerl-uollra;a aqt 6uo1e pessed uaqlere (zg6y3 pue) HCVN ruolJ suor])ala
16raue-q6rq'uor1e;,{roqdsoqd enrleprxojo ssa)oro aql ul '(uMoqs lou'zHCVlol CVI pue) HCVN ol +CVN sa)npel
qrrqnn'ap{t pt)e )ult) eqt,{q pazrloqelaruuaql st Vol llla)e aqf Vo:) ;i(1ate o1 umop
uolorq ere pue (woiloq uotJpuoq)oltu,laql ralua sprre I11e; pue alennr{6
'elrpuor,l)oltul u! Lus!loqelau 6ultereua6-[6raue ;o {leuurns y g 1-p 1 a.rn613
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aueJqu.Jaui letJpuoq)oltul JauuleueJquauj lerJpuoq)o}il.! lalno
aseqlu,{s dlv
NOTUCNOH)OllW tHrMitocondria - Geradores de energiaMembrana externa
Membrana interna
Mitocondria - Geradores de energia
1.Mitocondrias precisam de produtos manipulados pelo gene da célula (a maioria de suas proteínas)
2.Duplicação similar a duplicação assexuada de bactérias
3.Células que necessitam mais energia tem mais mitocondrias, e elas se multiplicam dependendo da necessidade da célula
4.Glicolise anaeróbia (nosso recurso do nosso DNA) produz aproveita 1/15 da energia do açúcar, obtido pela mitocondria.
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