INHIBITORS OF ETC & OXIDATIVE PHOSPHORYLATION

Dr Vijay Marakala M.D

Assistant professorBiochemistry

SIMS&RC

SHUTTLE SYSTEMS SUBSTRATE LEVEL PHOSPHORYLATION

INHIBITORS

Inhibitors of the ETC proper

Inhibitors of oxidative

phosphorylation [FoF1ATPase]

Uncouplers of oxidative

phosphorylation

INHIBITORS OF ETC PROPER

INHIBITORS OF ETC PROPER

Complex-IComplex-IIIComplex-IV

Blocking ETC Proton pumping

ATP synthesisOxygen uptake

Results in block

Inhibitors of first site or complex-I

NAD FMN Fe-S CoQ Cyt.b Fe-S Cyt.c1Cyt.c Cyt.aa3 O2

Antibiotic

Barbiturates

InseCticide

• Piericidin

• Amobarbitol

• Rotenone

Inhibitors of second site or complex-III

NAD FMN Fe-S CoQ Cyt.b Fe-S Cyt.c1 Cyt.c Cyt.aa3 O2

Dimercaprol

Antimycin A

Inhibitors of second site or complex-IV

NAD FMN Fe-S CoQ Cyt.b Fe-S Cyt.c1 Cyt.c Cyt.aa3 O2

Cyanide

CO

H2S

Inhibitors of oxidative phosphorylation

Block Phosphorylation directly by inhibiting FoF1ATPase

Oligomycin Dicyclohexyl carbodiimide

[DCCD]

Uncouplers of oxidative phosphorylation

Uncouplers of oxidative phosphorylation

2,4 Dinitrophenol[DNP]

Dicumarol

Chlorocarbonylcyanide phenylhydrazone[CCCP]

Salicylate

Thermogenin

THERMOGENIN a natural

uncouplerH+

SHUTTLE SYSTEM FOR

EXTRAMITOCHONDRIAL NADH

Transport of reducing equivalents from cytosol

Inner mitochondrial membrane is not permeable to cytoplasmic NADH

Shuttle system for oxidation of Extramitochondrial NADH

Malate – aspartate shuttle

Glycerol phosphate shuttle

Malate – aspartate shuttle

Glycerol phosphate shuttle

36 or 38

Substrate level phosphorylation

Substrate level phosphorylation

ENERGY CURRENCY OF CELL

ATP

ADP

ADP+Pi

AMP+Pi

AMP Adenosine+Pi

G0= -7.3Kcal/mole

G0= -7.3Kcal/mole

G0= 3.4Kcal/mole

There are three major sources of taking part in energy

conservation or energy capture:

Oxidative phosphorylation

Glycolysis

TCA cycle

Role of ATP/ADP cycle in transfer of high-energy phosphate

There will be a test on Wednesday

[9am-10am] MQ-1 [10 marks]

S/N-2 [5X2=10 marks]