Introduction to the study of cell biology

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Transcript Introduction to the study of cell biology

Chapter 6
Mitochondria : Energy Conversion
Mitochondria: in all eukaryotic cells
Mit: Oxidative phosphorylation → ATP
ZHOU Yong
Department of Biology
XinJiang Medical University
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Teaching Requirements
• 1. Mastering: ultrastructure of mitochondria;
function of mitochondria: oxidative
phosphorylation.
• 2. Comprehending: relationship between structure
and function of mitochondria.
• 3. Understanding: genomes of mitochondria;
proliferation of Mitochondria
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I. Distribution of Mitochondria
The size and number of mitochondria reflect the
energy requirements of the cell.
Figure. Relationship between mitochondria and
microtubules.
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Figure. Localization of mitochondria near sites of high ATP
utilization in cardiac muscle and a sperm tail.
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Figure. Mitochondrial
plasticity.
Rapid changes of
shape are observed
when a mitochondrion
is visualized in a living
cell.
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Figure. Fractionation of purified mitochondria into separate
components.
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II. Mitochondrial ultrastructure
(1) Inner membrane
(2) Out membrane
(3) Intermembrane space
(4) Matrix
Inner and outer mitochondrial membranes enclose
two spaces: the matrix and intermembrane space.
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Electron micrograph
of a mitochondrion
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1.Ribosome
2.Cristae
3.DNA
4.ATP synthase
particles
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The inner membrane is folded into Cristae
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Some morphology of mitochondrial cristae
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ATP synthase particles
Elementary particles
F0-F1 ATPase complex
F0-F1 coupling factor
1. Head sector
2. Stalk sector
3. Membrane sector
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The structure of the ATP synthase particle
Molecular basis of phosphorylation
F1 particle is the catalytic subunit;
The F0 particle attaches to F1 and is
embedded in the inner membrane.
F1: 5 subunits in
the ratio
3:3:1:1:1
F0: 1a:2b:12c
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Outer membrane:
Contains channel-forming protein, called Porin.
Permeable to all molecules of 5000 daltons or less.
Inner membrane (Impermeability):
Contains proteins with three types of functions:
(1) Electron-transport chain: Carry out oxidation reactions;
(2) ATP synthase: Makes ATP in the matrix;
(3) Transport proteins: Allow the passage of metabolites
Intermembrane space:
Contains several enzymes use ATP to phosphorylate
other nucleotides.
Matrix: Enzymes; Mit DNA, Ribosomes, etc.
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III. Oxidative
phosphorylation
Fig. Three stages of cellular
catabolism that via controlled
“burning” conserve energy for
use in heterotrophic cells.
Food is hydrolysed into small
molecules in the cytoplasm.
Glycolysis is also cytoplasmic.
Pyruvate and other substrates
are taken up by mitochondria
under aerobic conditions and
through TCA - Krebs cycle and
electron transport converted
into waste molecules and
products ATP and NADH.
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Localization of metabolic functions within the mitochondrion
Outer membrane:
Phospholipid synthesis
Fatty acid desaturation
Fatty acid elongation
Matrix
Pyruvate oxidation
TCA cycle
ß oxidation of fats
Inner membrane:
Electron transport
Oxidative phosphorylation
Metabolite transport
Intermembrane space
Nucleotide phosphorylation
DNA replication, RNA transcription,
Protein translation
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Complete lysis of glucose can be divided into
four steps:
1. Glycolysis
2. Formation of the acetyl CoA
3. Tricarboxylic acid cycle (TCA)
4. Oxidative phosphorylation
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ATP molecule: energy currency or energy carrier
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A. Glycolysis
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Fig. Summary of
glycolysis.
• glycolysis can provide
sufficient energy for
growth of anaerobic
organisms and tissues,
or autotrophic cells in
the dark.
• the reactions only
partially oxidize
glucose to ethanol or
pyruvate
• occur in cytoplasm.
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B. Formation of the acetyl CoA
1. Pyruvate enter into mitochondrial matrix from cytoplasm.
2. Catalyzed by pyruvate dehydrogenase
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C. Tricarboxylic
acid cycle (TCA)
Krebs cycle
Citric acid cycle
1. Occur in mitochondrial
matrix.
2. Require oxygen.
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Fig. TCA (tricarboxylic
acid) cycle.
MAIN FUNCTIONS:
•oxidation of substrates
•reduction of cofactors
•substrate level
phosphorylation
•regeneration of acceptor
•release of 3CO2 per turn
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The main points to remember:
1.The cycle uses acetyl CoA as the immediate substrate
- this can come from beta oxidation of fatty acids OR
from pyruvate via glycolysis.
2.The products are reducing molecules NADH and
FADH2; GTP; CO2 and a molecule of oxaloacetate is
regenerated.
3.One way of describing the stoichiometry of the TCA
cycle is as follows:
Glucose + 6H2O + 10NAD+ + 2FAD + 4ADP + 4Pi ——>
6CO2 + 10NADH +10H+ + 2FADH2 + 4ATP + 4H2O
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Net result of the glycolytic pathway and the citric acid cycle
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D. Oxidative phosphorylation
1. Electron carriers (cofactors)
(1) nicotinamide adenine dinucleotide (NAD)
R=H
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(2) Flavoproteins
a. flavin mononucleotide (FMN)
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b. flavin adenine dinucleotide (FAD)
Oxidized form
Reduced form
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(3) Ubiquinone
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(4) Cytochromes
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(5) Iron-sulfur proteins
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2. Electron-transport chain (respiratory chain)
Electron-carrying prosthetic groups in the respiratory chain
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Mitochondrial electron
transport chain shown
in the context of redox
potential (I.e. free
energy content per
electron) of the
components.
Most of the energy is
CONSERVED in the
proton gradient and
membrane potential this energy is
harvested in the next
step, by the ATPase
complex.
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Primary and secondary electron-transport chains
NADHO2: 3ATP/2e;
FADH2 O2 : 2ATP/2e
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3. ATP synthesis
Energy contained in the
reduced molecules
formed in TCA cycle is
converted into high
energy of ATP by:
1) ELECTRON
TRANSPORT CHAIN
(forming a proton
gradient and
membrane potential)
and B) proton gradient
dissipating ATPase
which SYNTHESIZES
ATP.
2) SUBSTRATE LEVEL
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PHOSPHORYLATION
F1 particles have ATP synthase activity
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Mithchell’s Chemiosmotic theory (1961)
The electrochemical gradient resulting from transport of
protons links to oxidative phosphorylation.
When electrons are transported along the chain, the H+ is
translocated across the inner membrane.
The mitochondrial inner membrane is impermeable to H+ .
When protons flow in the reverse direction through the
F1-F0 coupling factor complex, the potential energy is
released. It drive ATP synthesis.
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Inhibitors affect the respiratory chain and
ATP synthesis in mitochondia
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Summary of the major activities during aerobic
respiration in a mitochondrion
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IV. Mitochondrial semi-independence
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IV. Mitochondrial proliferation
Direct division of
Mitochondria in mouse
liver cell
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REVIEW QUESTIONS
• 1. Describe the main opinions briefly about
Mithchell’s Chemiosmotic theory.
• 2. Describe the ultrastructure of
Mitochondrion.
• 3. Compare the permeability of outer
membrane and inner membrane of
Mitochondrion.
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