Física do Corpo Humano - USPFísica do Corpo Humano Prof. Adriano Mesquita Alencar Dep. Física...

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


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


(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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(B)

Rlrt4

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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


(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

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E269

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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Transporte através de

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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$,

river \\ \bed

' f l ow ingstrea m

a

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.

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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.











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












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

http://www.nature.com/scitable/topicpage/mitochondria-14053590

http://www.nature.com/scitable/topicpage/mitochondria-14053590


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


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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

activatedca rnermoleculesstoreenergy

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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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

I

NADH fromglycolysis

IOzI

CozI

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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NOTUCNOH)OllW tHrMitocondria - Geradores de energiaMembrana externa

Membrana interna


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.

Física do Corpo Humano - USPFísica do Corpo Humano Prof. Adriano Mesquita Alencar Dep. Física...

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Transcript of Física do Corpo Humano - USPFísica do Corpo Humano Prof. Adriano Mesquita Alencar Dep. Física...