Chapter 10: Carbohydrate Metabolism II: Aerobic Respiration Flashcards
Why is cyanide poisonous?
Cyanide binds irreversibly to cytochrome a/a3 in the electron transport chain, inhibiting aerobic respiration from yielding ATP the body requires to function properly.
It renders cells unable to utilize oxygen for aerobic respiration because it blocks oxygen from binding to the ETC.
Difficulty breathing, weakness, cardiac arrest in high doses, death within minutes.
Image from Pearsons re metabolism that helps orient the processes and shows products of metabolism.
Describe the electron shuttles after glycolysis.
After glycolysis, electrons are shuttled across the mitochondrial membrane using malate-aspartate or glycerol-3-phosphate shuttles because the inner mitochondrial membrane is impermeable to NADH, the primary electron carrier from glycolysis.
Glycolysis from Pearson
Citric acid cycle from Pearson
ETC from Pearson
ETC and chemiosmosis from Pearson
Pyruvate as a key juncture in catabolism Pearson
Control of cellular respiration Pearson
Catabolism of various molecules Pearson
Amino acids feed into the citric acid cycle after their carbon skeletons are converted into intermediates like acetyl-CoA, pyruvate, alpha-ketoglutarate, succinyl-CoA, fumarate, or oxaloacetate, which are then used to generate energy or as precursors for other metabolic pathways.
What is the citric acid cycle? Other names for it?
Where does it do?
What does it produce?
How is acetyl CoA obtained for the citric acid cycle?
Occurs in the mitochondria, its main function is the oxidation of acetyl CoA to carbon dioxide and water.
The citric acid cycle produces high energy electron carrying molecules NADH and FADH2.
Acetyl CoA can be obtained from metabolism of carbohydrates, fatty acid, and amino acids.
Is acetyl CoA important?
Yes.
Where does pyruvate go after a glucose undergoes glycolysis?
Pyruvate enters the mitochondrion via active transport and is oxidized and decarboxylated by a multi enzyme complex called pyruvate dehydrogenase complex, located in the mitochondrial matrix.
What is the overall reaction of the pyruvate dehydrogenase complex?
Is it exergonic or endergonic?
What is it inhibited by?
Take note that a carbon is lost from pyruvate, forming acetyl CoA and CO2.
3C pyruvate to 2C acetyl CoA and CO2
Exergonic (deltaG= -33.4 kJ/mol).
Inhibited by accumulation of acetyl CoA and NADH.
How can acetyl CoA be produced?
Glycolysis
Fatty acid oxidation (beta oxidation)
Amino acid catabolism
Ketones
Alcohol consumption (alcohol dehydrogenase and acetaldehyde dehydrogenase) convert alcohol to acetyl CoA. Primarily used for synthesis of fatty acids.
What is the difference between coenzyme A and acetyl CoA?
What are the pyruvate dehydrogenase complex enzymes needed to catalyze acetyl CoA in sequential order?
What forms of energy does the brain use?
MCAT concept check acetyl CoA 10.1 page 380 question 1
What is the overall reaction of the pyruvate dehydrogenase complex?
MCAT concept check acetyl CoA 10.1 page 380 question 2
Citric acid cycle
Why is oxygen important for the citric acid cycle?
Checkpoints and regulation of the citric acid cycle
What are the products of the citric acid cycle?
How many net ATP are wrought through glycolysis, the citric acid cycle, and then eventually oxidative phosphorylation?
Mnemonic for the substrates of the citric acid cycle
What are the eight key reactions of the citric acid cycle?
Citrate formation
Citrate is isomerized to isocitrate
Alpha Ketoglutarate and CO2 formation
Succinyl CoA and CO2 formation
Succinate formation
Fumarate formation
Malate formation
Oxaloacetate formed anew
Step 1 of the citric acid cycle
Citrate formation.
2C acetyl Coa and 4C oxaloacetate makes 6 carbon citrate and CoA.
Condensation reaction, yielding citrate CoA-Sh, catalyzed by citrate synthase.
Recall that synthases are enzymes that form new covalent bonds without needing significant energy.
Step 2 citric acid cycle
Citrate isomerized to one of four isomers of isocitrate, the goal being d isocitrate.
Step 3 citric acid cycle
RATE LIMITING Alpha ketoglutarate and CO2 formation
Isocitrate is oxidized to oxalosuccinate, oxalosuccinate decarboxylated to alpha ketoglutarate.
Step 4 citric acid cycle
Succinyl CoA and CO2 formation carried out by alpha ketoglutarate dehydrogenase complex (similar in mechanism, cofactors, and coenzymes to the pyruvate dehydrogenase complex).
Produces NADH and CO2.
Step 5 citric acid cycle
Succinate formation.
Hydrolysis of the thioester bond of succinyl CoA yields succinate and GTP CoA-SH.
Succinyl CoA synthetase catalyzes this. (Synthetases create new bonds with energy input, unlike synthases).
The energy required for the synthetase to work is found in the high energy thioester bond of succinyl CoA.
THIS IS THE ONLY TIME IN THE ENTIRE CITRIC ACID CYCLE THAT ATP IS PRODUCED DIRECTLY. The GTP produced in this reaction is transformed into ATP by nucleosidediphosphate kinase.
Step 6 citric acid cycle
Fumarate formation.
It doesn’t take place in the mitochondrial matrix, occurs on the inner membrane.
Succinate oxidation to fumarate by succinate dehydrogenase, an integral protein in the inner mitochondrial membrane.
FAD is reduced to FADH2. Each molecule of FADH produces 1.5 ATP (NADH produces 2.5 ATP)
FAD is the electronic acceptor in this reaction because the red reducing power of succinate is not great enough to reduce NAD+.
Step 7 citric acid cycle
Malate formation.
Fumarase catalyzes the hydrolysis of the alkene bond of fumarate to form L malate.
Step 8 citric acid cycle
Malate dehydrogenase reduces NAD+ to make NADH by the oxidation of malate to produce oxaloacetate.
Which steps of the citric acid cycle produce NADH? FADH2? ATP directly?
Where does the fourth NADH come from?
Step 3, 4, and 8 produce one NADH.
Step 6 produces FADH2.
Step 5 produces ATP
The fourth NADH comes from the Pyruvate dehydrogenase complex.
What are the net products of glycolysis, the pyruvate dehydrogenase complex, and the citric acid cycle?
How many ATP are made from this?
Which molecules have a negative feedback effect on the citric acid cycle?
High energy molecules (ATP) and energy carriers (NADH and FADH2), which are products of the process.
Citrate also inhibits the citric acid cycle (krebs cycle and tricarboxylic acid cycle)
Do synthases require energy? Do synthetases?
What classification of enzyme are dehydrogenases?
What should we immediate think when seeing a dehydrogenase?
Dehydrogenases are oxidoreductases (they catalyze redox reactions).
Dehydrogenases transfer a hydride ion (H-) to an electron acceptor like NAD+ and FAD.
Whenever we see a dehydrogenase in aerobic metabolism, look for a high energy electron acceptor being formed.
Pyruvate dehydrogenase complex regulation.
What are the control points of the citric acid cycle?
Speak about ATP and NADH and its role in the citric acid cycle.
MCAT concept check citric acid cycle 10.2 page 387 question 1
What is the purpose of all the reactions that collectively make up the citric acid cycle?
Complete oxidation of carbons and intermediates to CO2 so that reduction reactions can be coupled with CO2 formation, thus forming energy carrier such as NADH and FADH2 for the electron transport chain.
MCAT concept check citric acid cycle 10.2 page 387 question 2
What enzyme catalyze the rate limiting step of the citric acid cycle?
Isocitrate dehydrogenase, step 3.
MCAT concept check citric acid cycle 10.2 page 387 question 3
What is the electron transport chain?
What does it do?
Where does it occur?
The electron transport chain is the final pathway that utilized electrons from our energy source (füd).
The flow of electrons happen in a step wise fashion to allow for smaller portions of manageable energy to be exploited rather than one large energy transfer.
The ETC occurs in the mitochondrion and involves the intermembrane space, the inner mitochondrial membrane, and the mitochondrial matrix.
The complexes, or the energy producing machinery, involved in the ETC are embedded in the inner mitochondrial membrane.
Where does glycolysis, fermentation, and the citric acid cycle occur?
Glycolysis and fermentation occur in the cytosol.
The citric acid cycle takes place in the mitochondrial matrix.
How are the citric acid cycle and the ETC linked directly?
Step 6 of the citric acid cycle, the oxidation of succinate to fumarate through succinate dehydrogenase, actually occurs at complex 2 of the electron transport chain.
FADH2 is covalently bonded to complex 2, meaning the oxidation of FADH2 for the electron transport chain happens inside of complex 2.
What are the folds within the inner mitochondrial called? Why for?
The inner mitochondrial membrane is assembled into folds called cristae (kris-tay), which maximize surface area.
What is the proton motive force?
The proton motive force is an electrochemical proton gradient generated by the complexes of the electron transport chain.
What is the final step in aerobic respiration?
Describe aerobic respiration.
The electron transport along the inner mitochondrial membrane and the generation of ATP via ADP phosphorylation.
These two processes are separate, but they are coupled so they are often explained together.
NADH and FADH2 are form is byproducts at earlier steps and respiration. They transferred their electrons to carry your proteins located along the inner mitochondrial membrane, using oxygen is the final electron acceptor, forming water.
Energy released from transporting electrons facilitates, proton transport at three locations in the chain.
Protons are moved into the intermembrane space, creating a greater concentration gradient of hydrogen ions that can be used to drive ATP production.
Endergonic or exergonic:
The electron transport chain
Formation of ATP
Why important?
ETC: endergonic
ATP synthesis: exergonic
They coupling these reactions, the energy yielded by one reaction can fuel the other.
The electron transport chain is a series of oxidation and reductions that occur via the same mechanism. NADH and FADH2 are good electron donors (FADH2 being a weaker reducing agent than NADH)
What is complex 1 of the ETC?
What does it do?
How is it unique?
NADH CoQ oxidoreductase.
The transfer of electrons from NADH to coenzyme Q is catalyzed in the First complex.
Three noteworthy sub units are a flavoprotein that oxidizes NADH, a protein that has an iron-sulfur cluster and coenzyme Q
The flavoprotein has a coenzyme called flavin mononucleotide (FMN) covalently bonded to it that is similar to FAD.
All three, the FMN (first), the iron-sulfur clusters (second), and CoQ (final), undergo oxidation reduction reactions that ultimately lead to pumping 4 H+ out of the inner mitochondrial matrix.
What is the net reaction of complex 1 of the ETC?
What is the effect of the redox reactions of complex 1?
The effect is 4 H+ ions pumped out of the mitochondrial matrix.
What is complex 2 of the ETC?
What do?
How unique?
What effect?
Succinate CoQ oxidoreductase
Linked to the step 6 of citric acid cycle. Succinate oxidizes to fumarate via succinate dehydrogenase, reducing FAD to FADH2. This is super interesting. It uses covalently bonded FAD as an electron acceptor because the oxidizing strength of succinate is insufficient to reduce NAD+.
FADH2 then gets oxidized to FAD as it reduces another iron-sulphur protein.
The final step is oxidation of the Fe-S complex to reduce CoQ.
NO H+ PUMPING IN COMPLEX 2.
What is the net reaction for complex 2?
How many H+ ions pumped?
No H+ are transferred out of the mitochondrial matrix from the redox reactions in complex 2.
What is complex 3 of the ETC?
What do? How unique? Why for?
CoQH2 cytochrome c oxidoreductase (aka cytochrome reductase)
Transfers electrons from CoQ to cytochrome c in a few steps.
Redox of CYTOCHROMES: proteins with heme groups in which iron is reduced to Fe2+ and oxidized to Fe3+.
The electron transfers from iron only involves one electron per reaction, but because coenzyme Q has two electrons to transfer, two cytochrome C molecules are needed.
Transfers four H+ out of the mitochondrial matrix.
What is the Q cycle of complex 3 of the ETC?
Complex 3 main contribution to the proton motive force is via the Q cycle.
Two electrons are shuttled from a molecule of ubiquinol (CoQH2) near the enter membrane space to a molecule of ubiquinone (CoQ) near the mitochondrial matrix.
Another two electrons are attached to heme moieties, reducing two molecules of cytochrome c.
A carrier containing iron and sulfur assists this process.
Four protons are displaced to the inter membrane space during the redox reactions of complex three.
What is the net reaction of complex 3 of the ETC?
Are coenzyme Q and cytochrome c technically part of the complex complexes of the electron transport chain?
Both CoQ and cyt c are not technically part of the complexes. However, because both are able to move freely in the mitochondrial membrane, this degree of mobility allows these carriers to transfer electrons by physically interacting with the next component of the transport chain.
What is complex 4 of the ETC?
What do? Why important? Is unique?
Cytochrome c oxidase
Facilitates the culminating step of the electron transport chain: transfer of electrons from cytochrome C to oxygen.
Include subunits of cytochrome a, cytochrome a3, and copper ions (Cu2+).
Cyt a and a3 make up cytochrome oxidase.
Cytochrome oxidase gets oxidized as oxygen is reduced to water.
Two H+ are moved across the membrane.
What is the net reaction of complex 4 of the ETC?
How many H+?
What complex does cyanide inhibit?
Cyanide is an inhibitor of cytochrome subunits a and a3.
The cyanide and ion is able to attach to the iron group and prevent the transfer of electrons.
Tissues that rely heavily on aerobic respiration such as the heart in the central nervous system can be greatly impacted.
What is the proton motive force?
A proton gradient is formed as electrons were passed along the electron transport chain.
This causes two things:
PH drops in the intermembrane space.
The voltage difference between the membrane space and matrix increases due to proton pumping.
These two changes contribute to what is referred as an electrochemical gradient. Electrochemical gradients store energy.
Because it is based on protons, we often refer to the electrochemical gradient across the inner mitochondria membrane has the proton motor force.
This particular electrochemical gradient will be responsible for providing the energy to ATP synthase to form ATP from ADP and an inorganic phosphate.
ATP yield per glucose ranges between 30 and 32. Why?
What are the two shuttle mechanism responsible for this and why?
Efficiency of aerobic respiration varies between cells.
This variable efficiency is caused by the fact that cytosolic NADH formed through glycolysis cannot directly cross into the mitochondrial matrix, meaning it cannot contribute its electrons to the transport chain directly.
The alternative means of transportation of these electrons is referred to as shuttle mechanisms.
The two shuttle mechanisms that transfer the high energy electrons of NADH to a carrier that can cross the inner mitochondrial membrane are:
Glycerol 3 phosphate shuffle
Malate-aspartate shuffle
What is the glycerol 3 phosphate shuttle?
Because NADH formed through glycolysis cannot directly cross into the mitochondrial matrix, it must find alternate means of transportation called shuttle mechanisms. Glycerol 3 phosphate is one of those shuttle mechanisms.
What is the malate-aspartate shuttle?
Because NADH formed through glycolysis cannot directly cross into the mitochondrial matrix, it must find alternate means of transportation called shuttle mechanisms. Malate-aspartate shuttle is one of those shuttle mechanisms.
Image of the glycerol 3 phosphate and malate-aspartate shuttle.
MCAT concept check electron reality chain 10.3 page 396 question 1
MCAT concept check electron reality chain 10.3 page 396 question 2
What role does the electron transport chain play in the generation of ATP?
The electron transport chain generates the proton motive force, an electrochemical gradient across the inner mitochondrial membrane which provides the energy for ATP synthase to function.
MCAT concept check electron reality chain 10.3 page 396 question 3
Based on its needs, which of the two shuttle mechanisms is cardiac muscle most likely to utilize? Why?
The malate-aspartate shuttle.
Because this mechanism is the more efficient one, it makes sense for a highly aerobic organ, such as the heart to utilize it in order to maximize its ATP yield.
Why are only a small fraction of the 100 polypeptides that are necessary for oxidative phosphorylation and encoded by the mitochondrial DNA?
A small fraction, 13/100 polypeptides necessary for oxidative phosphorylation, are encoded by mitochondrial DNA.
The significance of this fact is that mitochondrial DNA has a mutation rate nearly 10 times higher than that of nuclear DNA
The link between ETC and ATP synthesis starts with what enzyme?
ATP synthase, which spans the entire inner mitochondrial membrane and protrudes into the matrix.
What is the portion of ATP synthase that spans the membrane?
The F0 portion functions as an ion channel and spans the entire inner mitochondrial membrane.
Protons travel through F0 along their gradient back into the matrix.
What is chemiosmostic coupling?
Chemiosmotic coupling describes the direct relationship between the proton gradient and ATP synthesis.
Chemiosmotic coupling allows the chemical energy of the proton gradient to be harnessed as a means of phosphorylating ADP, forming ATP.
The ETC generates a high concentration of protons in the inter membrane space; the protons then flow through the F0 ion channel of ATP synthase back into the matrix, where F1 phosphorylates ATP.
What is the F1 portion of ATP synthase?
What does it do?
The F1 portion of ATP synthase utilizes the energy released from the electrochemical gradient to phosphorylate ADP to ATP.
What is conformational coupling?
Conformational coupling suggests that ATP is released by the synthesis as a result of confirmational changed caused by the gradient.
This proposed mechanism suggests the F1 portion of ATP synthase is reminiscent of a turbine, spinning with a stationary compartment to facilitate the harnessing of gradient energy for chemical bonding.
What is the free energy change of the reaction of ATP synthase?
Regarding ATP synthesis, what are uncouplers?
Aspirin?
Uncouplers are compounds that prevent ATP synthesis without affecting the electron transport chain, decreasing the efficiency of the ETC/oxidative phosphorylation pathway.
ADP builds up and ATP synthesis decreases, the body responds to this perceived lack of energy by increasing O2 consumption and NADH oxidation.
The energy produced from the transport of electrons is released as heat.
An example would be the fever experienced with toxic levels of salicylates, or aspirin.
Always think of O2 and ADP as the key regulators of oxidative phosphorylation. Explain.
Always think of O2 and ADP as the key regulators of oxidative phosphorylation.
If O2 is limited, the rate of oxidative phosphorylation decreases, and the concentrations of NADH and FADH2 increase.
The accumulation of NADH inhibits the citric acid cycle.
The coordinated regulation of these pathways is known as respiratory control.
In the presence of adequate O2, the rate of oxidative phosphorylation is depending on the availability of ADP as the concentration of ADP and ATP our reciprocally related. Thus, ADP accumulation signals the need for ATP synthesis.
ADP allosterically activates isocitrate dehydrogenase (step three of the citric acid cycle) increasing the rate of the citric acid cycle and production of NADH and FADH2.
The elevated levels of NADH and FADH2 (reduced coenzymes) increase the rate of electron transport and ATP synthesis.
What is the relationship between ADP and isocitrate dehydrogenase?
Isocitrate dehydrogenase is step three of the citric acid cycle and is the rate limiting step of the citric acid cycle (alpha ketoglutarate and CO2 formation and reduction of NAD+ to form NADH).
This step, catalyzed by isocitrate dehydrogenase, is regulated by ADP and ATP, with ADP stimulating and ATP inhibiting the enzyme.
MCAT concept check oxidative phosphorylation 10.4 page 398 question 1
What is the difference between the electron transport chain and oxidative phosphorylation?
What links the two?
MCAT concept check oxidative phosphorylation 10.4 page 398 question 2
MCAT mastery chapter 10 aerobic metabolism page 372 question 1
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