Class-1 (18/10) : introduction , redox pair

thermodynamics
high energy compounds
shuttle pathways

Class-2 (22/10) :enzymes and co-enzymes

involved
electron transport chain(ETC)

Class 3 (25/10) : ETC

Oxidative phosphorylation & theories
inhibitors and uncouplers

Class 4 (29/10) : SGD

 High energy compounds
High Energy rich compounds Energy release G in
in KJ/mol kcal/mol
Phosphate compounds
1. ATP to ADP + ppi -30.5 -7.3
2.Creatinine phosphate -43.1 -10.5
3. 1,3 bisphosphoglycerate -49.4 -10.1
4.Phosphoenel pyruvate -61.9 -14.8
Sulfur compounds
1.coA derivatives
Acetyl coA ,succinyl coA , fattyacyl coA -7.5
SAM -10.0
Low energy compounds
ADP to AMP+ ppi -45.6 kJ -6.6kcal
Glucose-1-phosphate -5.0
Fructose 6-phosphate -3.8
Glucose 6-phosphate -3.3
Primary metabolism Secondary Tertiary
metabolism metabolism

INTESTINE TCA CYCLE ETC

Carbohydrates Glu Acetyl Co A

Lipids FA ATP
CO2
Proteins AA
H2 O

NADH
 Sources of NADH
• GLYCOLYSIS : 2 NADH

• PREP STEP : 2 NADH

• KREBS CYCLE : 6 NADH 2 FADH2

BETA OXIDATION : PALMITIC ACID :

7 NADH 7 FADH2
PROTEOLYSIS
 MITOCHONDRIA

CYTOSOL
2
ATP
6 NADH & 2 FADH
ATP
ADP

2 NADH Citric
acid H+ H+
cycle H+
O2 H 2O
GLYCOLYSIS H+
Glucose-----2 pyruvate
2 Acetyl CoA 2 NADH

2 2 pyruvate

ATP O2 Hb
 MITOCHONDRIA
CYTOPLASM Malate shuttle INNER
MEMBRANE
NADH OAA

NAD malate malate

NAD
ETComplex 1
NADH
Glycerol-3-p shuttle Dehydrogena
NADH
se
NADH DHAP OAA
FADH2
e- CoQ
NAD FAD
G3-P
Cyt b/c1

O2
INTERMEMBRANE
SPACE COMPLEX-4/ Cyt a/a3
Cyt c oxidase
Cyt c
Cyt-C
1 Heme HEME
GROUP- a, a 3
INNER Resike centre
QH2 FO
MEMBRANE 3 Fe-S 2 Fe-S
Copper
Cyt-b1
GROUP-A, B
2 Heme

FMN
F1
Fe-S COMPLEX-3/ Cyt b/c1
Q – Cyt c oxidoreductase COMPLEX-5
COMPLEX-1
NADH-Q oxidoreductase FADH2
ATP synthase

MATRIX COMPLEX-2
Succinate-Q reductase
 4 H+ 4 H+ 2 H+

INTERMEMBRANE Cyt c
SPACE 4e-

INNER Fes
QH2 Cyt b Heme a+a3
FO
MEMBRANE Cyt c1 CuA CuB
FMN

4 H+ O2 2H2O
F1
NADH + H+ NAD+ Fes
COMPLEX-5
ATP synthase
MATRIX FAD

Complex II
ENERGETICS OF OXIDATIVE PHOSPHORYLATION

NAD+ /NADH [E0 = -0.32] ; ½ O2/H2O [E0 = +0.82]

½ O2 + NADH + H+ H2O + NAD+

Redox potential difference = 1.14v ~ 52 kCal/mol

(200kJ/mol)

GO = -nf EO = 200KJ/mol

Synthesis of 1 ATP = 7.3kcal/mol or 30KJ/mol

so, for 200KJ = 7 ATP should be produced but we get

only 2.5
 4 H+ 4 H+
INTER
2 H+
MEMBRANE
SPACE
H+

Cyt c
G-3-P 4e- H+
e-
INNER e- e -

MEMBRANE
Fes
QH2 Cyt b/c1 Heme a+a3

FMN CuA CuB FO

e -

Succinate-Q
oxidoreductase
4 H+ O2 2H2O F1
NADH + H+ NAD+
3H+

MATRIX
ADP + Pi ATP
 MECHANISM OF OXIDATIVE PHOSPHORYLATION

 Chemical coupling Hypothesis

Edward Slater

Phosphorylated high-energy intermediates

 Chemiosmotic Hypothesis

Peter Mitchell

Proton Gradient
 β α
α
δ
β β

b2 γ
N- side έ

a c

P- side
Uncouplers OF OXIDATIVE PHOSPHORYLATION

Ex : 2,4 – dinitrophenol ; Dinitrocresol ; aspirin

trifluoro carbonylcyanide phenylhydrazone (FCCP)

Physiological Uncouplers :

 Thermogenin

 Thyroxine

 Long chain FA

 BROWN ADIPOSE TISSUE

 INHIBITORS OF ETC

INTERMEMBRANE COMPLEX-5
SPACE Cyt c
INNER COMPLEX-3
COMPLEX-1 QH2 COMPLEX-4 FO
MEMBRANE

F1
COMPLEX-2

MATRIX
rotenone Antimycin A Cyanide Atractyloside
malonate Dimercaprol Carbonmonoxide oligomycin
amytal
Barbiturates H 2S
 Inhibitors :Atractyloside
rotenone oligomycin
amytal Uncouplers : 2,4 DNP
Barbiturates aspirin
thermogenin
INTER thyroxin
MEMBRANE 4 H+ 4 H+
SPACE 2 H+
H+

Cyt c
G-3-P 4e- H+
e-
INNER e- e - Energy lost

MEMBRANE
Fes
QH2 Cyt b/c1 Heme a+a3
FO
as heat
without
FMN CuA CuB
e- ATP synthesis
Succinate-Q
oxidoreductase
4 H+ F1 H+ + 2,4 DNP
O2 2H2O
NADH + H+ NAD+
3H+

MATRIX
ADP + Pi ATP

Antimycin A Cyanide
Dimercaprol Carbonmonoxide
H 2S
 REGULATION

CONDITIONS LIMITING THE RATE OF RESPIRATION

Stage 1 Availability of ADP and substrate
Stage 2 Availability of substrate only
Stage 3 The capacity of respiratory chain
Stage 4 Availability of ADP only
Stage 5 Availability of oxygen

•If O2 is decreased – concentration of NADH and FADH2 increase – inhibits TCA

•If O2 is adequate – depends on the availability of ADP

•ATP and ADP are reciprocally related