Lecture 7.docx

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5 Feb 2013
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Mitochondria evolution
•Arose from phagocytosis of aerobic prokaryote
•Can divide in the cell
Mitochondrial fission
•“powerhouse of the cell”
Site of aerobic respirations
Mitochondria functions
•Site of aerobic respiration
Utilizes oxygen to extract energy from macromolecules and converting it to ATP
-Primarily from glucose: ATP production.
Mitochondria ATP production
•We use 2 X 1026 molecules of ATP a day
-ATP: cells energy source: energy is released when ATP is hydrolyzed to ADP
•Amount of mitochondria in cells depends on energy needs
•many mitochondria in: muscle cells, liver cells, fat cells, plant cells & sperm
Mitochondria Structure
•Usually sausage-shaped but can be spherical (early embryos) or elongate, threadlike
(fibroblasts)
-0.2 -2 um in cross-sectional diameter & 1-4 um in length (similar in size to bacteria)
•Size and number of mitochondria reflect energy needs of the cell
•Dynamic structures
Change shape, move from place to place in cytoplasm
•Mitochondria can fuse with one another, or split in two.
The balance between fusion and fission is likely a major determinant of mitochondrial
number, length, and degree of interconnection.
•Inner and outer mitochondrial membranes enclose two spaces
-The matrix and the Intermembrane space
•Outer mitochondrial membrane is outer boundary
•Inner mitochondrial membrane subdivided into 2 interconnected domains
- Inner boundary membrane
- Cristae: where the machinery for ATP is located
- Phase-contrast light microscope can be picked up
- Bright field stain:
- To see inner membrane structure light microscope is not enough: TEM, SEM
Outer Mitochondrial Membrane (OMM)
•~ 50% protein: very porous
•Porin proteins large channels : Bacteria-like Beta pleated sheets.
•Allows very large molecules in
Inner Mitochondrial Membrane (IMM)
•~ 75% protein
•Unusual lipid composition
-No cholesterol, rich in cardiolipin: typical of bacterial plasma membranes
-like bacterial plasma membranes
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•Highly impermeable
Requires channels and pumps
•Over 100 different proteins
Electron transport chain (ETC)
-IMM forms cristae-many thin folds to increase the surface area
Mitochondrial Matrix
•Gel-like, from high protein concentration
•Contains circular DNA molecule(s), ribosomes and tRNA
•Mitochondrial DNA encodes for 37 genes
•However, mitochondrial function requires 3000 proteins
Mitochondria proteins are completely translated on free ribosomes in cytosol
Proteins must then be imported into the mitochondria
Posttranslational uptake of proteins into mitochondria
•IMM integral proteins: includes all the proteins of the ETC and the ATP synthase.
•Matrix proteins: includes all the enzymes of the Krebs / citric acid cycle.
How do mitochondria make ATP?
•Start with Glucose (or amino acids, or glycerol and fatty acids)
•Series of chemical reactions
-Performed by enzymes (proteins)
Acts on substrates (targets) to produce a chemical change in the substrate
How do mitochondria make ATP?
•Start with Glucose (or amino acids, or glycerol and fatty acids)
1) Glycolysis: cytosol of the cell itself
2) Krebs cycle/Citric Acid/TCA Cycle: mitochondrial matrix
3) Electron-Transport Chain: Inner mitochondrial membrane (cristae)
Total Result of Aerobic Respiration: C6H12O6+ 6O2=6C02 +6H2O + 38 ATP
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1) Glycolysis
•Glucose (6 C) –contains high energy electrons
First hydrolyzed into 2 molecules of pyruvate/pyruvic acid (3 C)
Involves 10 chemical reactions by enzymes
Steps 1 3) Glucose is phosphorylated, rearranged structurally
and then phosphorylated again (cost = 2ATP)
Steps 4 5) 6C biphosphate is split into two 3C monophosphates
Step 6) 3C aldehyde oxidized to an acid and e-used to reduce
NAD+ to NADH and C1 is phosphorylated
Step 7) phosphate group from C1 is transferred to ADP forming
ATP (gain = 2ATP)
Steps 8 9) rearrangement and dehydration of substrate
Step 10) phosphate group transferred to ADP forming ATP (gain
= 2ATP)
Glucose + 2NAD+ + 2 ADP + 2Pi 2 Pyruvate+ 2 ATP + 2 NADH
+ 2 H++ 2 H2O
•Pyruvic acid then moves to mitochondrial matrix: through a
special pyruvate transporter
•Converted to a 2 C molecule called acetyl CoA : (one CO2 and
one NADH also generated)
2) Krebs / TCA / citric acid cycle
•It is a stepwise cycle where substrate is oxidized and its energy
conserved.
•Acetyl CoA bound to a 4 C molecule (OAA) to create citrate (6
C)
•During the cycle, two carbons are oxidized to CO2,
regenerating the four-carbon OAA needed to continue the cycle.
•OAA then attached to an incoming Acetyl CoA and cycle
continues.....
•Contains many enzymes for this conversion
•Enzymes break down carbon molecules through oxidation
reactions: loss of electrons: electrons are from H atoms in c
molecules
Step 1 : NAD+ and FAD become reduced
•ie., NAD+ becomes NADH
•Molecules within cycle are common compounds generated in
other catabolic reactions
Krebs/TCA/citric acid cycle = central metabolic pathway of the
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