Cell Respiration
● Breaking down glucose slowly
○ Glycolysis, krebs cycle
○ Activation barrier- enzymes, yields mostly energy
○ 1 glucose molecule makes 38 molecules of ATP
● Redox
○ Oxidation: losing e-
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○ Reduction: gaining eThe fuel, glucose, gets oxidized
○ E- lose potential energy along the way
○ By oxidizing glucose, respiration takes energy out of storage to make it available
to ATP synthesis
○ Food would spontaneously combine with O2 if it weren't for the high activation
energy
○ Glucose is oxidized in steps, gradually
NAD+ gets reduced
○ Dehydrogenase enzymes transfer e- from substrate to NAD+
○ NAD+ is oxidizing agent
Oxygen
○ In ETC, it has a high electronegativity
○ Can pull e○ Without Oxygen
■ can only go as far as pyruvate
■ Anarobic
■ Fermentation reaction
Fermentation
○ In yeast: makes alcohol
○ In muscles, it makes lactic acid
NAD+
○ Coenzyme
○ Must need e- and H+, must be harvested
○ Dehydrogenase
■ Enzyme that strip substrate of 2 e- and 2 protons
● One proton gets released into surrounding solution
● 2 electrons and remaining proton are given to NAD
■ Makes NADH, carries 2e- and H+
Oxidative phosphorylation
○ ETC
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Energy is released at each step of the chain
Oxidative phosphorylation because it's powered by redox reactions that transfer
e- from food to oxygen
Substrate Level Phosphorylation
○ When enzyme transfers P-group from substrate to ADP
○ Phosphate donor is PEP, formed from breakdown of sugar during glycolysis
○ Glycolysis and Kreb's cycle
(1) Glycolysis
○ Anaerobic, does not require O2
○ Catabolic, starts with oxidation of glucose
○ Occurs in cytoplasm
○ Substrate level phosphorylation
○ Makes total of 4 ATP, 2 get recycled, 2 get used
○ Makes 2 NADH, goes off to e- transport chain
■ Adding electrons and protons to NAD+
○ 10 enzymes, a couple phases
○ Glucose can diffuse in and out of cell, we want to stop it from leaving
○ Phases
■ Energy investment
● Uses 2 ATP’s
● First 5 enzymes
■ Energy yield (payoff)
● Makes 4 ATPs by substrate-level phosphorylation
● Also makes 2 NADH
● End product of 2 Pyruvate (3C) and H2O
~~~Energy Investment~~~
○ 1) As soon as G enters cell, enzyme called hexokinase
■ Puts one phosphate group onto it, now it can't leave because phosphate
is charged
■ Makes it more reactive
○ 2) glucose turned into isomer fructose-6-phosphate
○ 3) Phosphofructokinase brings over second phosphate
■ Invests second ATP
■ Allosteric enzyme
● Regulates amount of ATP found in each cell
● Controls rate of cell respiration
○ 4) Next, aldolase cleaves sugar molecule into 2 3-carbon sugars
■ G3P and DHAD
○ 5) isomerase converts G3P to DHADH and vice versa
■ Only G3P is needed
~~~~Energy Payoff~~~~
○ 6) Sugar is oxidized by transfer of e- and H+ to NADH+, forming NADH
■ Extremely exergonic, uses released energy to attach phosphate group to
oxidized substrate
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■ Stored additional energy that can be used if oxygen is present
7) Phosphate group transferred to ADP in an exergonic reaction
8) enzyme relocates phosphate group
9) Enzyme extracts water
10) Phosphate group transferred to ADP, makes more ATP
■ Ends product of 2 pyruvates, 4 total ATP’s made
(2) Krebs Cycles
○ Most of energy remains in 2 pyruvates, which enter mitochondria if oxygen is
present
■ Completely breaks down glucose
■ Makes CO2, ATP, NADH, FADH2
○ Occurs in matrix; complete oxidation of glucose
■ 2 ATP molecules made by it
■ Aerobic, uses 02
○ Substrate-level phosphorylation
○ Pyruvate Oxidation
■ Takes place in mitochondrial matrix
■ First, pyruvate is turned into Acetyl Coenzyme A
● 1) carboxyl group removed as a molecule of CO2
● 2) Remaining 2C fragments oxidized to make acetate; e- are
transferred to NAD+, making NADH
● 3) coenzyme A attached to acetate by unstable bond, making it v
reactive
○ 2 carbons enter as acetate, 2 carbons leave as CO2
■ After each turn of the cycle
■ 1 pyruvate = 1 cycle
■ 1 glucose = 2 cycles = 2 ATP’s
○ Makes tons of NADH and FADH2
■ One yields more energy
○ 1) Acetate + Oxaloacetate (4C)= citrate
■ Oxaloacetate starts reaction, which makes it at the end
○ 2) citrate converted to isomer by removal of H2O and addition of another
○ 3) take CO2 out of isocitrate
■ Yields 2 e- which reduce NAD+
○ 4) another CO2 lost, another 2-, reduces another NAD+
■ Remaining molecule attached to coenzyme A w/ unstable bond
○ 5) CoA replaced w phosphate group
■ Transferred to GDP, making GTP, then to ADP, making ATP
■ Substrate-level phosphorylation
○ 6) 2 hydrogens transferred to FAD to make FADH2
■ Makes double bonds
○ 7) addition of water molecule
■ Rearranges bonds to make single bonds
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8) steal 2H and 2e- again, reducing NAD+, making oxaloacetate
Total products from single turn
■ 3 NADH
■ 1 ATP
■ CO2
(3) ETC
○ ((((each NADH can make 3 ATP; each FADH2 can make 2 ATP))))
○ Used to break the fall of e- to oxygen into several energy releasing steps
○ 90 percent of ATP made in ETC
○ Proteins built into inner membrane of mitochondria
■ Cristae is folded of lipid bilayer
■ The more folds, the more reactions
■ More than 1 chain
■ Things going on in membrane and inner-membrane space
○ When electrons flow, concentration of H+ in matrix decreases
■ There is a drop in free energy as e- flow down
○ Free-energy exchange during e- transport
■ Iron-sulfur protein passes e- to compound called ubiquinone, the only
lipid
■ Rest of protein btwn Q and oxygen are called cytochromes
■ Last cytochrome of chain, cyt a3, passes e- to oxygen, which picks up
pair of H ion to form water
○ Other reduced product of krebs cycle: FADH2
■ Adds e- at lower energy level than NADH
■ Provides ⅓ less energy
○ Doesn't make ATP directly
■ Releases energy in manageable amounts in smaller steps
○ Chemiosmosis
■ Protein complex called ATP synthase
● Works like an ion pump
■ Proton gradient drives oxidative phosphorylation
■ Chain is an energy converter that uses exergonic flow of e- to pump H+
across membrane
■ E- transfer causes H+ to be taken up and released
● H+ gradient that results is called proton motive force
■ Energy coupling mechanism that uses energy stored in form of H+
gradient to drive cellular work
■ O2 will pull e- past 2 proton pumps
■ E- slide down proton pumps
■ Pumps make steep proton gradient
■ FADH2 drops off e- further off
■ E- came from krebs cycle and glycolysis
■ Doesn't make ATP, makes energy to make ATP
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ATP synthase
○ Rotor
■ Spins when protons flow down gradient
○ Stator
■ Anchored in membrane
○ Rod
■ Also spins, activating catalytic sites
○ Knob
■ Catalytic sites
■ Join inorganic phosphate to ADP to make ATP
○ Direct energy source is electrochemical gradient of protons on opp. sides of the
inner memb space
Fermentation Reactions
○ Will be times when reactions do not have O2
■ Anaerobic, considered fermentation reactions
■ Can oxidize organic fuel and make ATP
■ Solely substrate-level phosphorylation
○ Glycolysis plus reactions that regenerate NAD+ by transferring e- from NADH to
pyruvates
○ Alcohol Fermentation
■ Yeast cells
■ Pyruvate converted to ethanol
● Releases CO2 and turns into acetaldehyde
● This is then reduced by NADH to ethanol
○ Lactic Acid Fermentation
■ In muscle cells
■ Pyruvate reduced directly by NADH to form lactate, no release of co2
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■ Lactate converted back to pyruvate by liver cells
○ Facultative anaerobes
■ Organisms that can survive using fermentation or respiration
Evolutionary SIgnificance of Glycolysis
○ First prokaryotes most likely produced ATP by glycolysis reactions
○ 3 reasons:
■ 1) glycolysis does not require oxygen; there wasn't any in early
environments
■ 2) glycolysis is most wide spread reaction (all organisms do it)
■ 3) occurs in cytoplasm, doesn’t need special organelles
If there is not enough glucose
If not enough glucose,
goes to FATS
Fatty Acids,
CR
Proteins can enter as
Amino Acids
GLUCOS
E
GLYCOL
PYRUVA
ACETYL
COA
ETC
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Fats, carbs, proteins can be broken down
Proteins
■ Can b converted to intermediates of glycolysis and krebs cycle
■ NH3 released
○ Fats
■ Energy stores in fatty acids
■ Beta oxidation breaks them down into 2C fragments that enter krebs
cycle as acetyl CoA
○ Carbs
■ Starch hydrolyzed to glucose
■ Glycogen can also be hydrolyzed
How to Control Rate of Respiration (3 ways)
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Phosphofructokinase
■ an allosteric enzyme
■ Inhibited by ATP
■ Stimulated by AMP
○ (1) Reacts to different amount of ATP
■ If too much ATP, turns PFK off (negative feedback loop)
■ If not enough ATP, will start making ATP
○ (2) citrate
■ If concentration too low, will stimulate PFK to make more
■ 2 conformations of citrate
○ (3) AMP
■ Will help stimulate PFK to work
Other points
○ Fermentation extends glycolysis, the first stage of metabolism, to produce
usable energy, while anaerobic respiration uses molecules other than oxygen
to complete the metabolic cycle.