Download What agents? What war?

5.19.06 OVERVIEW OF RESPIRATION AND LOOSE ENDS
What agents? What war?
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Ubiquinone or Coenzyme Q: small hydrophobic molecule that
can pick up or donate electrons
The respiratory chain contains 3 large enzyme complexes:
• each complex acts as an electron-transport-driven H+
pump
NADH dehydrogenase complex (22 polypeptide chains!)
• accepts electrons from NADH
• electrons are passed via a number of molecules including
ubiquinone (coenzyme Q or just Q) to the cytochrome b-c1
complex
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Cytochromes: family of proteins that are related by the
presence of a bound heme group whose iron atom changes from
Fe+3 to Fe+2 whenever it accepts and electron
Cytochrome b-c1 complex:
• accepts electrons from ubiquinone
• passes electrons to cytochrome c, which carries electrons to
the cytochrome oxidase complex
Cytochrome oxidase complex (cytochrome aa3):
• accepts electrons from cytochrome c and passes them to
oxygen
• also picks up a pair of protons to from water:
1/2 O2 + 2 H+ + 2e- ---> H2O
• The two components that carry electrons between the three major enzyme
complexes (ubiquinone and cytochrome c) diffuse rapidly in the plane of the
membrane
• The three enzyme complexes appear to function as independent entities in
the plane of the membrane
• Order of transfer of electrons is due entirely to the specificity of the
functional interactions among the components of the chain and the
tendancy of a specific component to be oxidized or reduced
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Electron transfer in the cytochromes involves metal ions such as Cu
and Fe
(A) The reaction of O2 with electrons in cytochrome oxidase
The iron atoms are linked to a heme residue (B)
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Back to cyanide
Cyanide affects virtually all body tissues, attaching itself
to ubiquitous metalloenzymes and rendering them
inactive
Principle toxicity probably results from inactivation of
cytochrome oxidase and thus oxidative phosphorylation
Oxygen dependent tissues (highest rate of respiration?) -brain, heart, liver -- are the most profoundly affected by
acute cyanide poisoning
Heme Found in what other protein?
Inhibitors of Oxidative Phosphorylation:
Inhibit cytochrome c oxidase by binding to its heme group
cyanide
azide carbon monoxide
lethal in small doses! [SeeMVH pg. 535 poisons]
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CORRECTION TO comment in Wednesday's lecture
Cytochrome C oxidase (last member of the electron
transport chain) :
1. reduces O2 to water
2. conserves the considerable free energy available from this
highly favorable reaction by pumping protons via three
independent proton pumping pathways (aka proton wires!)
H-bonding is always with us: net translocation of protons can occur over a “long
distance” through a protein by hopping between pairs of hydrogen bonded donor
and acceptor residues; a string of such residues connected by hydrogen bonds can
be thought of as a proton wire.....
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What can’t bacteria do?
Nature 441:274 May 18,2006
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In the case of aerobic respiration, used by
eukaryotes and many bacteria, the
terminal electron acceptor is molecular
oxygen
But in principle it could be any atom or
molecule that has a hunger for electrons
or at least more hunger than the atom or
molecule upstream in the electron
transfer chain!
See next page
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Back to the “regular” process…..
The complete oxidation of 1 mole of glucose generates about 38 moles
of ATP (synthesized from ADP)
ATP yield from complete oxidation of glucose
Process
Direct product
Final ATP
Glycolysis
2 NADH (cytosolic)
2 ATP
2 NADH
(mitochondrial matrix)
3 or 5*
2
5**
Pyruvate oxidation
(2 per glucose)
Acetyl CoA oxidation
(Citric Acid cycle)
two per glucose
6 NADH
(mitochondrial matrix)
2 FADH2
2ATP or 2 GTP
Total ATP yield
per glucose molecule
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3
2
30 -32***
* depends on which "shuttle system" transfers reducing equivalents into
the mitochondria
** check reference for # protons per ATP
*** This number varies from reference to reference..
Proton and ATP accounting
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Why is ATP “high energy”
ATP has stored potential energy:
ATP  ADP + Pi + energy
ΔGo = - 7.3 kcal/mole exergonic reaction
(corresponds to an Keq of >105
Under cellular conditions, the hydrolysis of ATP
creates two molecules of much lower energy and
releases a great deal of usable energy
1. The phosphates in ATP can be considered to
exist in an activated state: the presence of four
negative charges in close proximity destabilizes
the molecule -- electrostatic repulsion between
negative charges favors hydrolysis
2. Increased hydration ADP and P -- energetically
favored
3. Release of a phosphate increases entropy
because the PO4 molecule released is capable of
resonance forms (delocalized proton and
oxygen binding) not possible when phosphate is
bound to another molecule
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What do cells do with ATP?
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Drives anabolic (endergonic) chemical reactions
Used to do work (move stuff around)
used for active transport to make/maintain ion
and solute gradients
Lots of other roles
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Cells drive active transport in three main ways
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Remember lysosomes?
• Lysosomes contain hydrolytic enzymes that are
active under acidic conditions.
• The interior of this organelle is maintained at an
acidic pH (high proton concentration) by a H+
ATPase in the membrane that pumps protons
against the concentration gradient
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WHAT HAPPENS DURING GLUCOSE OXIDATION IF
NO OXYGEN IS PRESENT?
AEROBIC AND ANAEROBIC ORGANISMS
One basic metabolic distinction among organisms is
whether or not they can use O2 as an electron
acceptor in energy producing pathways
AEROBES: CAN USE O2
Obligate Aerobe: O2 is obligatory for life
ANAEROBES: CAN SUBSIST WITHOUT O2
Facultative Anaerobe: can adapt to anaerobic
conditions by substituting other electron
acceptors for O2 (yeast, bacteria)
Obligate Anaerobe: cannot use O2 and are poisoned by it
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BEAKER CONTAINS YEAST AND SUGAR
What is the gas being produced in the beaker?
WHAT HAPPENS DURING GLUCOSE OXIDATION IF
NO OXYGEN IS PRESENT?
Cell has a limited amount of NADH which must be
recycled if glycolysis is to continue under anaerobic
conditions
FERMENTATION: an anaerobic biological reaction
process
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FERMENTATION: THE ANAEROBIC FATE OF PYRUVATE
Commercially Valuable fermentation reactions:
Alcoholic fermentation by yeast used in brewing
and winemaking
Bacteria also can carry out alcoholic
fermentation under anaerobic conditions
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This type of fermentation occurs in some fungi and bacteria
(used to make yogurt and cheese) and in human muscle cells
when oxygen is limiting
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The three common metabolic fates of pyruvate generated by
glycolysis:
1. Under aerobic conditions, the pyruvate is completely
oxidized via the citric acid cycle to CO2 and H2O [NADH acts
as a high energy compound]
2. Under anaerobic conditions, pyruvate must be converted to
a reduced end product in order to reoxidize the NADH
produced by the GAPDH reaction
• alcoholic fermentation: in yeast, pyruvate is converted to
ethanol + CO2 [free energy of NADH oxidation is dissipated
as heat]
• in muscle cells, under anaerobic conditions, pyruvate is
reduced to lactate [free energy of NADH oxidation is
dissipated as heat]
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FERMENTATION: an anaerobic biological
reaction process in which a reduced organic
compound (like glucose) acts as an electron
donor and another organic compound acts as
an electron acceptor
An even more formal definition of fermentation
fermentation: catabolic reactions producing ATP in which
organic compounds serve as both the primary electron donor and
ultimate electron acceptor and ATP is produced by substrate
level phosophorylation
Note: fermentation is extremely inefficient
compared to aerobic respiration.
From first principles: Why?
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The potential energy drop between glucose and an
electron acceptor like pyruvate is a fraction of the
potential energy drop that occurs during cellular
respiration where O2 is the electron acceptor
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