Fisica do Corpo Humano (4300325)

Prof. Adriano Mesquita Alencar Dep. Física Geral

Instituto de Física da USP

Enzimas e Mitocondria Aula 13 e 14

B08

Fisica do Corpo Humano (4300325)

Princípios Físicos Aplicados à Fisiologia (PGF5306-1)

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.

66C

hapt

er 2: C

ell C

hem

istr

y and B

iosy

nthe

sis

otec

ul e

mol

ecul

em

olec

ule

mol

ecul

em

orec

ure

mot

ecut

eA

BB

RE

VIA

TED

A

5o-

o-o-

a-a-

o- ca

taly

sis by

enzy

me 1

enzy

me 2

en

zym

e 3en

zym

e 4en

zym

e 5

Figu

re 2-

34 H

ow a

set o

fenz

yme-

cata

lyze

d rea

ctio

ns ge

nera

tes a

met

abol

ic pa

thw

ay. E

ach e

nzym

eca

taly

zes a

part

icul

ar ch

emic

al re

actio

n, leav

ing th

e enz

yme u

ncha

nged

. In th

is ex

ampl

e, a se

t of e

nzym

esac

ting i

n se

ries

conv

erts

mol

ecul

e A to

mol

ecul

e F, fo

rmin

g a m

etab

olic

path

way

.

Cel

l Met

abol

ism

ls O

rgan

ized

by E

nzym

esTh

e ch

emic

al r

eact

ions

that

a c

ell c

arrie

s ou

t w

ould

nor

mal

ly o

ccur

onl

y at

muc

h hi

gher

tem

pera

ture

s tha

n th

ose

exis

ting i

nsid

e ce

lls. F

or th

is re

ason

, eac

hre

actio

n re

quire

s a sp

ecifi

c boo

st in

che

mic

al re

activ

ity. T

his

requ

irem

ent i

s cr

u-ci

al, b

ecau

se it

allo

ws

the

cell

to c

ontro

l eac

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 cir

cle,

as in

the y

el/o

w bo

x in

Figu

re 2-

34. T

he pa

thw

ay th

at is

high

light

ed 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

actio

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











Mitocondria - Geradores de energia1.Mitocondria são organelas atípicas 2.Elas se duplicam independentemente das células que

residem (seres unicelulares procarionte) 3.Ocupa um volume substancial do citoplasma 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

5.São nosso gerador de energia 6. A mitocondria permite15 vezes mais energia que o

ciclo de glicolise (respiração anaeróbia)http://www.nature.com/scitable/topicpage/mitochondria-14053590

Capitulo 14 do Livro de Molecular Biology, Alberts

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


(A) A light micrograph of chains of elongated mitochondria in a living mammalian cell in culture. The cell was stained with a fluorescent dye (rhodamine 123) that specifically

labels mitochondria in living cells. (B) An immunofluorescence micrograph of the same cell stained (after fixation) with fluorescent antibodies that bind to microtubules. Note that

the mitochondria tend to be aligned along microtubules. (Courtesy of Lan Bo Chen.)

Molecular Biology of the Cell. 4th edition.


Figure 14-6 Localization of mitochondria near sites of high ATP utilization in cardiac muscle and a sperm tail: During the development of the flagellum of the sperm tail, microtubules wind helically around the axoneme, where they are thought to help localize the mitochondria in the tail; these microtubules then disappear, and the mitochondria fuse with one another to create the structure shown.

Molecular Biology of the Cell. 4th edition.


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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1. NADH se liga com o Complexo I, e libera libera um atome de Hidrogênio (H+) e um elétron (e-), e retorna para o ciclo de Krebs.

2. Mesmo para FADH no complexo II 3. elétrons passa pela cadeia de

complexos proteicos, cada complexo, o elétron fica mais fortemente ligado. Nos complexos I, III e IV o elétron doa parte de sua energia para transportar prótons

4. No complexo IV o elétron se combina com O2 e H+ para formar H2O, produto final da respiração.

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).

pyruvate

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2e I u^rDAi lvE- -

PHOSPHORYLATIONtMITOCHONDRION

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NOTUCNOH)OllW tHrMitocondria - Geradores de energiaMembrana externa

Membrana interna



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.

&

q

1w

CO, + HrO CO, + HrO



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,

oHrc -t - s-coA

acetyl CoA2Ct

o x d t o a c e l a l e ./4C STEP 1

- ) lu4lllil-,,/+ H * V

/ srEP 8I

4C

* {srEP 2 5C

\ r*E!E--srEP 3

f.- co,I

5C

NET RESULT ONE TURN OF THE CYCLE PRODUCES THREE NADH, ONE GTB ANDONE FADH2, AND RELEASES TWO MOLECULES OF COI

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).


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.

Fisica do Corpo Humano (4300325)

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