Mitochondria and Cell

Respiration
dr. Isra Thristy, M.Biomed

DEPARTMENT OF BIOCHEMISTRY
FACULTY OF MEDICINE
UNIVERSITAS MUHAMMADIYAH SUMATERA UTARA
2017
Learning Issues :
 The process of the respiratory chain
 The function of the respiratory chain
 Mitochondrion

 Double membrane, with

inner membrane very
impermeable

 TCA occurs in the matrix

 ETC in the inner

membrane
Respiratory Chain

 Respiratory chain is in cristae of the inner membrane.

 Spontaneous electron transfer through respiratory chain complexes I, III &
IV is coupled to H+ ejection from the matrix to the intermembrane space.
 Because the outer membrane contains large channels, these protons
may equilibrate with the cytosol.
 Respiration-linked H+ pumping out of the matrix conserves some of the
free energy of spontaneous e- transfers as potential energy of an
electrochemical H+ gradient.
Estimated Daily Use of ATP

(g ATP/g tissue)
 Heart 16
 Brain 6
 Kidneys 24
 Liver 6
 Skeletal Muscle (rest) 0.3
 Skeletal Muscle (running) 23.6
 Cells use GTP and CTP, as well as UTP and ATP, to form activated
intermediates.
 Different anabolic pathways generally use different nucleotides as their
direct source of high phosphate bond energy:
 UTP is used for combining sugars,
 CTP in lipid synthesis, and
 GTP in protein synthesis.
 The high-energy phosphate bonds of UTP, GTP, and CTP are energetically
equivalent to ATP and are synthesized from ATP by nucleoside
diphosphokinases and nucleoside monophosphokinases.
 Energy from fuel oxidation is converted to the high-energy phosphate bonds
of adenosine triphosphate (ATP) by the process of oxidative phosphorylation.
 Most of the energy from oxidation of fuels in the TCA cycle and other
pathways is conserved in the form of the reduced electron-accepting
coenzymes, NADH and FAD(2H).
 The electron transport chain oxidizes NADH and FAD(2H), and donates the
electrons to O2, which is reduced to H2O.
 Energy from reduction of O2 is used for phosphorylation of adenosine
diphosphate (ADP) to ATP by ATP synthase (F0 ATPase).
 The net yield of oxidative phosphorylation is approximately 2.5 moles of ATP
per mole of NADH oxidized, or 1.5 moles of ATP per mole of FAD(2H) oxidized.
Electron Transport Chain: Proteins
Electron transport
chain
Complex I
Alternate Entries

Complex II
(aka succinate
dehydrogenase)
Alternate Entries
Complex III
Complex IV

Fig 19-14
Chemiosmotic
Mechanism

Electron
transport chain
sets up an H+
gradient (proton
motive force).
Energy of the
pmf is harnessed
to make ATP.
Inhibitors of electron transport

Fig 19-6
 Fatigue can result from iron-defeciency anemia, which
decreases Fe for Fe-S centers and cytochromes.
 Cytochrome c2 oxidase, which contains the O2 binding site,
is inhibited by cyanide.
 Mitochondrial DNA (mtDNA), which is maternally inherited,
encodes some of the subunits of the electron transport chain
complexes and ATP synthase.
 Oxphos diseases are caused by mutations in nuclear DNA or
mt DNA that decrease mitochondrial capacity for oxidative
phosphorylation.
 ATP synthesized from oxidative phosphorylation is actively transported
from the matrix to the intermembrane space by adenine nucleotide
translocase (ANT).
 Porins form voltage-dependent anion channels (VDAC) through the outer
mitochondrial membrane for the diffusion of H2O, ATP metabolites, and
other ions.
 Under certain types of stress, ANT, VDAC, and other proteins form a
nonspecific open channel known as the mitochondrial permeability
transition pore. This pore is associated with events that lead rapidly to
necrotic cell death.
 Clinical aspects

 Fatal infantile mitochondrial myopathy and renal

dysfunction  due to severe diminution / absence
of most oxidoreductase
 MELAS (mitochondrial encephalopathy, lactic
acidosis and stroke)  due to complex I or
complex IV deficiency  mutation in mt DNA
Referensi

 Textbook of Biochemistry with Clinical Correlations, Devlin MT, Willey Liss, 2002/5th
ed.
 Harper’s Biochemistry, Murray RK,Granner DK, Mayes PA, Lange MedicalBooks, Mc
Graw-Hill, 2003/26th ed.
 Lippincott's illustrated reviews biochemistry, Denise r ferrier, 2014