ETC

INTRODUCTION:
  • The final common pathway in aerobic cells by which electrons derived from various substrates are transferred to oxygen.
  • Enzymes of ETC are present in inner mitochondrial membrane.
  • 4 complexes:
  1. Complex I : NADH- CoQ oxidoreductase
  2. Complex II: Succinate- CoQ reductase
  3. Complex III: CO-Cytochrome Coxido reductase (Q-Cycle)
  4. Complex IV: Cytochrome-COxidase
SEQUENCE OF ELECTRON CARRIER:
  • Sequence of electron carriers in the mitochondria in electron transport chain: Substrate → NAD*→ FAD ├áCO enz. Q → 2cyt b → 2 cyt C1 → 2 cyt C → 2cyt (a+a3) → O2
  • The redox potential in the ETC is in increasing order except in the case of ubiquinone (Co enzyme Q).
  • Sequence:
  1. Q accepts electrons via complex I and complex II
  2. The Q cycle couples electron transfer to proton transport in complex III
  3. Molecular oxygen is reduced to water via complex IV
  4. Complexes I, III and IV act as proton pumps.
  5. Flavoproteins are important components of Complexes I and II.
  • H2S inhibits complex IV
  • Action of physiological uncoupler is Inhibition of ATP synthesis only not ETC
  • The oxidized flavin nucleotide (FMN or FAD) involves the transfer of two electrons (to form FMNH2 or FADH2) or they accept one electron to form the semiquinone.
  • Iron-sulfur proteins (non heme iron proteins, Fe-S) are found in Complexes I, II, and III.
  • Inhibitor of FOF1 ATPase in Electron transport chain is Oligomycin
COMPOUND AFFECTING ELECTRON TRANSPORT:
  • Compounds which affect electron transport chain and oxidative phosphorylation

Complex I to Co-Q specific inhibitors Complex II to Co-Q
Alkylguanides (guanethide), hypotensive drug
Rotenone, insecticide and fish poison
Barbiturates (amobarbital), sedative
Chlorpromazine, tranquilizer, Guanethedine
Piericidin, antibiotic
Carboxin
TIFA,
Malonate (competitive inhibitor)
Complex III to cytochrome c inhibitors Complex IV inhibitors
BAL (British anti lewisite), antidote of war gas Naphthoquinone
Antimycin, Phenformin
Carbon monoxide, inhibits cellular respiration
Cyanide (CN-)
Azide (N3-)
Hydrogen sulphide (H2S)
Site between succinate dehydrogenase & Co-Q Inhibitors of oxidative phosphorylation
Carboxin, inhibits transfer of ions from FADH2
Malonate, competitive inhibitor of succinate DH
Atractyloside, inhibits translocase
Oligomycin, inhibits flow of protons through Fo lonophores, e.g. Valinomycin
Uncouplers Physiological uncouplers
2,4-dinitrophenol (2,4-DNP)
2,4-dinitrocresol(2,4-DNC)
CCCP(chlorocarbonylcyanidephenyl hydrazone)
Thyroxine, in high dosesThermogenin in brown adipose tissue

  • The classic poisons H2S, carbon monoxide and cyanide inhibit Complex IV and can therefore totally arrest respiration.
  • Cyanide inhibits electron flow, proton pumping, and ATP synthesis.
  • Role of molecular oxygen in ETC To act as last electron acceptor
  • Action of physiological uncoupler is Inhibition of ATP synthesis only not ETC
  • Malonate is a competitive inhibitor of Complex II.
  • Fatal infantile mitochondrial myopathy and renal dysfunction: severe diminution or absence of most oxidoreductases of the respiratory chain.
  • In ETC, Oxidative phosphylartion (ATP formation) is regulated by NADH Co-Q reductase, Cytochrome C oxidase, Co-Q-Cytochrome C reductase
  • MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADH-Q oxidoreductase (Complex I) or cytochrome oxidase (Complex IV) deficiency
 Exam Question
  • In ETC, Oxidative phosphylartion (ATP formation) is regulated by NADH Co-Q reductase, Cytochrome C oxidase, Co-Q-Cytochrome C reductase
  • Role of molecular oxygen in ETC To act as last electron acceptor
  • Complex II is not associated with liberation of energy
  • ETC occurs in mitochondria generates ATP & transport reducing equivalent
  • Action of physiological uncoupler is Inhibition of ATP synthesis only not ETC
  • H2S inhibits complex IV
  • Inhibitor of FOF1 ATPase in Electron transport chain is Oligomycin
  • In ETC, complex-4 is inhibited by CO, CN?,H2S, azide
Don't Forget to Solve all the previous Year Question asked on ETC