介紹12級生物化學(xué)

生物化學(xué)新陳代謝篇OxidativePhosphorylationNADH

in

the

cytoplasmCitrate;

Isocitrateα-Ketoglutarate檸檬酸循環(huán)造成NADH的積累SuccinateSuccinyl-CoA依賴于氧化磷酸化來解決Not

too

difficult,

because

citric

acid

cycle

occurs

within

the

mitochondronEnzyme

complexesBinding

of

a

NADH

molecule

to

complex

Iand

the

donation

of

twoelectrons.FMN

+

2H+

+

2e?

FMNH23.

The

electrons

are

then

transferred

through

aseries

of

iron-sulfur

clusters,

during

which

four

protons

are

pumped

from

the

matrix

intothe

intermembrane

space.4.

Finally,

the

electrons

are

transferred

fromthechain

of

iron–sulfur

clusters

to

a

Q

molecule

inthe

membraneIntermembrane

spaceMatrixComplex

I:A

pair

of

electrons

pump

out

4

protons2

QH2

oxidized

to

2

Q1

Q

reduced

to

QH22

Cyt

c1

reduced4

H+

released

into

intermembranespace2

H+

picked

up

from

matrixComplex

II:2

pairs

of

electrons

pump

out

4

protons1

pair

of

electrons

pump

out

2

protonsElectron

transfer

through

Complex

IV

isfrom

cytochromec

to

the

CuA

center,

toheme

a,

to

the

heme

a3-CuB

center,

andfinally

to

O2For

every

four

electrons

passing

throughthis

complex,

the

enzyme

consumes

four"substrate"

H+

from

the

matrix

inconverting

O2

to

2H2OIt

also

uses

the

energy

of

this

redoxreaction

to

pump

one

proton

outward

into

theintermembrane

space

for

each

electron

thatpasses

through,

adding

to

the

lectrochemicalpotential

produced

by

redox-driven

protontransport

through

Complexes

I

and

III.Complex

IV:A

pair

of

electrons

pump

out

4

protonsIn

total,

the

successive

transfer

2

electrons

from

1

NADHthrough

complexes

I,

II,

IV

pump

out

10

protons.4

protons

result

in

1

ATP1

NADH

~

2.5

ATPHow

about

NADH

in

the

cytoplasm?糖酵解造成NADH的積累GlucosePyruvate2NAD+存在的問題：NAD+

很快會消耗殆盡?？赏ㄟ^無氧呼吸部分解決2NADH無氧呼吸：Alcoholic

fermentation無氧呼吸：Lactic

acid

fermentation這些無氧呼吸雖然能將部分NADH變?yōu)镹AD+,但效率很低氧化磷酸化效率很高，需要充分利用但存在問題NADH

cannot

simply

pass

into

mitochondria

for

oxidation

by

the

respiratorychain,

because

the

inner

mitochondrial

membrane

is

impermeable

to

NADHand

NAD+.解決方案Many

shuttles

transfer

electrons

from

NADH

to

the

respiratory

chain.For

example,

glycerol

3-phosphate

shuttleActive

in

the

brain

and

skeletal

musclesDHAPE-FAD:

FAD

bounded

with

enzymeThe

process

is

similar

to

lactate

fermentation1. The

enzyme

glycerol

3-phosphate

dehydrogenase

(in

the

cytoplasm)

catalyzesNADH

NAD+,

while

transfer

two

electrons

to

form

glycerol

3-phosphateThe

enzyme

glycerol

3-phosphate

dehydrogenase

(in

the

outer

surface

ofinner

mitochondrial

membrane)

catalyzes

glycerol

3-phosphate

Dihydroxyacetone

phosphate,

while

transfer

two electrons

to

form

FADH2.FADH2

transfer

electronsto

Q

to

form

QH2.Coenzyme

Q

(lipid

solvable)Not

exactly

the

same

enzymeDiffer

in

aminoacid

sequenceCatalyze

the

same

reactionwith

different

kineticsglycerol

3-phosphateglyceraldehyde-3-phosphate(GAP)One

cytoplasmic

NADH

produces

how

many

ATP:

2.5

or

1.5?1.51. Although

it

is

NADH,

it

does

not

go

throughcomplex

I

pathway2.

Complex

I

pathway

canpump

out

4

protons,

which

contributesabout

1

ATP4H+3.

So,

it

produces

about

1.5

ATPs,instead

of

2.5.Is

there

any

way

to

get

away

with

this

waste?The

malate-aspartate

shuttleActive

in

the

liver

and

cardiac

musclesOne

NADH

produces

2.5

ATPsWhy

the

brain

does

not

use

malate-aspartate

shuttle,

which

is

more

efficient?In

fact,

the

shuttle

is

bidirectionalWe

actually

encountered

the

reverse

direction

beforeOxaloacetatePhosphoenolpyruvatePyruvateSo

the

problem

is

actually

which

direction

is

dominated.And

it

is

determined

by

the

ratio

NADH/NAD+ In

the

liver

and

heart,

NADH/NAD+

is

higherin

the

cytosol

than

in

the

mitochondrionSo

the

direction

shown

in

the

leftIn

the

brain

and

skeletal

muscle,

NADH/NAD+

is

lower

in

the

cytosol

than

in

the

mitochondrionSo

the

reverse

directionThey

have

to

use

glycerol

3-phosphateATP-ADP

translocaseWhy

ATP

out

of

the

matrix

but

ADP

into

the

matrix?1.

ATP

concentration

in

the

matrix

is

higher

than

that

in

the

cytosol2.

ATP4?

is

morenegative

than

ADP3?So

ATP

is

easier

to

go

outward,

approaching

the

positive

outer

surfaceOf

the

inner

mitochondrial

membrane.+

+

+

+

+

+

++

+

+Energy

Yields

from

Oxidative

Metabolism4

ATP10

NADH2

FADH2+4

ATP10*2.5

=

25

ATP2*1.5

= 3

ATP=

32