BIOCHEMISTRY

Biological Oxidation(Electron Transport Chain)

Balance of electric (electrostatic) charge in molecule mostly

determined by electron (e–).

Electron is a particle with elementary negative charge.

In some processes in organic molecules charge balance is

determined by the proton (H+). [Proton is charged positively].

Oxidation is defined as the loss of electrons –e– and reduction

as a gain of electrons +e–.

Biological oxidation – also named as respiration – it is an

ATP-generating process in which an inorganic compound

serves as the ultimate electron (e–) acceptor (i.g. O2 [i.e. during

biological oxidation O2 reduced to H2O]). The electron donor

can be either an organic compound or inorganic one.

Standard redox

potential (E0) of

some oxidation-

reduction systems

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Mitochondria

Mitochondria are

oval-shaped cell

organelles, contain

the respiratory

assembly – that is the

enzymes of the citric

acid cycle, and the

enzymes of fatty acid

oxidation.

Mitochondria are

typically about 2μm

in length and 0.5μm

in diameter

Mitochondria electron microscope photo

Distribution of protons H+ – between matrix and

intermembrane space [inner crista space] forms electrostatic

potential on inner mitochondria membrane.

Four complexes of mitochondria electron transporting

chain and (fifth) ATP-synthesis complex.

[NADH and Succinate-Fumarate entrances into ETC]

Cellular respiration and biological oxidation based on

NADH and FADH2 (which are gained from: glycolysis, pyruvate

processing, citric acid cycle, amino acid oxidation, and β-oxidation

Sugars (carbohydrates) are the main oxidation substrate

Two main possible ways of sugar oxidation[energy gradient during biological oxidation and direct burn of sugar]

Amino

Acids

enter

TCA

Glycolysis

Pyruvate processing 1

Pyruvate processing (phases)

Coenzyme A (3 parts of CoA)

nucleotide, panthotenic acid (Vitamin B5), β-mercapto

ethylamine)

CAC

[TCA]

Krebs

cycle

CAC (Krebs Cycle)

Electron Transport Chain sequence

Levels of Redox

potendial and Free

energy in Electron

Transport Chain

Complexes

Chemical potential energy decreasing in ETC

Electron Transport Chain [I, III, IV] proton pomp

Electron Transport Chain [with potential gradient]

Complexes I-II-III-IV, V in Electron Transport Chain

Complex I in Electron Transport Chain 1

NADH ubiquinone

oxidoreductase (Complex I)

[usually have ‘L’ shape

consists of 46 polypeptides]

NADH – is an oxidized

molecule

Ubiquinone – is reduced

Complex I acts as proton pomp

Complex I in Electron Transport Chain

[this complex is pumping H+ into intermembrane

space: each NADH+H+ – give two protons 2H+]

Source of NADH+H+ for complex I :

-Glycolysis

-TCAcycle

-Amino Acid oxidation

-β-oxidation

All of these reactions increas concentration of

NADH+H+, which is transporting into mitochondrial

matrix, where it is oxidated by enzyme oxidoreductase

NADH+H+ → NAD+

in the same time FMN is reducing:

FMN(oxidated form) → FMNH2 (reduced form)

Nicotinamide dinucleotid (NAD)

Nicotinamide

(niacin – Vitamin B3)

ribose

Adenine

ribose

Nicotinamide dinucleotid (NAD) oxidated form

Nicotinamide dinucleotid (NAD+)

oxidation of niacin (Vitamin B3 part)

Hydrogen stereospecifically trasferred by NADH

(reduced form) dehydrogenases

[NAD+ is an oxidised form]

reduced form

Flavin Mono Nucleotide

(FMN)[reduced form is shown here ]

dimethylisoalloxazine

(flavin)

ribose

Reduction of dimethylisoalloxazine (flavin)

in Flavin mono nucleotide (FMN)

reduced form

oxidized form

Complex I with the help of FMN and Iron-Sulfur

centers [clusters] (Fe–S) do transfer electron

to Ubiquinone (reducting it into Ubiquinol)

FMNred → FMNox

Fe+3–S(ox) → Fe+2–S(red)Ferric (+3) oxidized form → Ferros (+2) reduced form

Fe+2–S(red) → Fe+3–S(ox)

…

Fe+3–S(ox) → Fe+2–S(red)

Fe+2–S(red) → Fe+3–S(ox)

…

Coenzyme Qn (Ubiquinone(ox))→ Coenzyme QnH2 (Ubiquinol(red))

this all increasing ubiquinol pool

Molecular models of iron-sulfur complex: (A) cluster

containing one Fe; (B) containing [2Fe-2S] cluster;

(C) [4Fe-4S] cluster. Iron atoms are shown in red, cistein sulfur

atoms shown in yellow; inorganic sulfur atoms in green.

Iron-sulfur complex: cluster containing

one Fe; containing [2Fe-2S] cluster;

[4Fe-4S] cluster

Coezyme Q10 – 1 (electron carrier)

isopren segments

Coezyme Q10 – oxidized and reduced forms

(with intermediate semiquinone form)

[to be reduced receives 2 electrons (from Complex I

or Complex II) and 2 protons (from matrix)]

Complex II (Succinate dehydrogenese) of ETC

Complex II do not transfer

protons (H+) into intermembrane

space

but reduces FAD to FADH2 and

through Fe-S clusters reduce

coenzyme Q10 (to ubiquinol)

Succinate dehydrogenese

(it is the same enzyme as in TCA cycle)

Succinate (alkane) oxidized to (alkine) Fumarate

Adenin mono

phosphat

(AMP)

Flavin Adenin

Dinucleotide (FAD)

[dimethylisoalloxazine]

Flavin

([ribo]flavin – Vitamin B2)

Structure of FAD(ox) – FADH2(red)

Flavin part of

Flavin adenin

dinucleotide

(FAD) is active

part of molecule

– oxidized

(consists of

flavin

mononucleotid

(FMN) unit

[green] and

adenin mono

phosphate

(AMP) [red]

Flavin adenin

dinucleotide

(FAD) oxidized

(consists no

hydrogen)

dimethylisoalloxazine in FAD [oxidized]

and in FADH2 [redused]

Iron Sulfur center (Fe–S) in Complex II in ETC

Succinate → FumarateFAD(ox) → FADH2(red)

Ferric (+3) oxidized form → Ferros (+2) reduced form

Fe+3–S(ox) → Fe+2–S(red)

Fe+2–S(red) → Fe+3–S(ox)

…

Fe+3–S(ox) → Fe+2–S(red)

Fe+2–S(red) → Fe+3–S(ox)

…

Coenzyme Qn (Ubiquinone(ox))→ Coenzyme QnH2(Ubiquinol(red))

this all increasing ubiquinol pool

Complex III in Electron Transport Chain

Cytochrome c Ubiquinol

oxidoreductase [Q cycle]

12 polypeptide chains

Complex III do transfer

protons (2H+) into

intermembrane space

Cytochrome c Ubiquinol oxidoreductase [Q cycle]

Complex III

QH2 →–→ e → 2Fe–2S

2Fe–2S→Heme c→Cytochrome c(red)→complex IV

e– → Heme blowpotencial → Heme bhighpotencial

Semiquinol intermediate radical

[Q` ubiquinol with one electron]

Heme (AmE) or haem (BrE) is a cofactor has an Fe2+ (ferrous) ion in the

middle of a large heterocyclic organic ring called a porphyrin, made up

of 4 pyrrolic groups joined together by methine bridges(5,10,15,20).

Not all porphyrins contain iron, but a

substantial fraction of porphyrin-

containing metalloproteins have heme

as their prosthetic group; these are

known as hemoproteins. Hemes are

most commonly recognized as

components of hemoglobin, the red

pigment in blood, but are also found in

a number of other biologically

important hemoproteins such as

myoglobin, cytochrome, catalase, and

endothelial nitric oxide synthase.

The heme in cytochrome c and c1 is covalently

attached to two cystein side chains

The heme b structure

Complex IV in Electron Transport Chain

Cytochrome c oxidaze

Complex IV do transfer

protons (2H+) into

intermembrane space

Cytochrome reductaze

(main phases of electron transferring)

Three-dimensional structure of reduced cytochrome c.The heme group (red), methionine 80 (green), histidine 18 (blue), and the

α-carbon atoms are shown. [from tuna]

Cytochrome. The heme group histidine and oxygen atoms are shown.

Chemical redox

potential and free

energy of

compounds

decreasing through

ETC.

Gradient of protons (pH) on inner membrane of

mitochondria

ATP [adenosine triphosphate]

[GTP]guanine

triphosphate

ATP synthase

ATP synthase and arrangment

of gens encoding the subunits

of ATP synthase in E.coli. This

cluster of genes is called

uncoupled operon (unc)

ATP synthase

Complex V

ATP synthase – the three catalytic sites cyclr through

three conformational states: O [open], L[loose

binding], T [tight binding]. Proton flux through the

syntase drives this interconversion of states. The

essence of this proposed mechanism is that proton flux

lead to the release of tightly bound ATP.

ATP

synthase 1

ATP

synthase

interacting with

actin

filament

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