ETC

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 àCO 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
  • Complexes I, III and IV act as proton pumps.
  • 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 doses
  • Thermogenin 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

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