Module 6: V7 - V11 Flashcards
What is the importance of the PDH complex?
can be considered as the 1st control point of the Krebs cycle
Why are B group vitamins important?
used extensively in metabolism
What is the first reaction of the Krebs cycle? Is this reaction exergonic or endergonic?
the formation of citrate from oxaloacetate and acetyl-CoA
the reaction is highly exergonic because it involves the hydrolysis of a thioester
What is the second reaction of the Krebs cycle? Is this reaction exergonic or endergonic?
citrate is converted to isocitrate in two-steps (via a cis-aconitate intermediate) catalyzed by aconitase
unfavourable yet driven to the right by the rapid consumption of isocitrate in the cycle
What is the third reaction of the Krebs cycle? Is this reaction exergonic or endergonic?
isocitrate is then converted to a-ketoglutarate by isocitrate dehydrogenase producing CO2 + NADH
exergonic + irreversible
What is the fourth reaction of the Krebs cycle? Is this reaction exergonic or endergonic?
a-ketoglutarate is converted to succinyl-CoA by the a-ketoglutarate dehydrogenase complex
exergonic + irreversible
What is the fifth reaction of the Krebs cycle? Is this reaction exergonic or endergonic?
succinyl-CoA is then converted to succinate by succinyl CoA synthetase
exergonic
What is the sixth reaction of the Krebs cycle? Is this reaction exergonic or endergonic?
succinate is converted to fumarate by succinate dehydrogenase which produces FADH2
not exergonic or endergonic, instead = 0
What is the seventh reaction of the Krebs cycle? Is this reaction exergonic or endergonic?
fumarate is converted to L-malate via a carbanion intermediate by the enzyme fumarase
exergonic
What is the eighth reaction of the Krebs cycle? Is this reaction exergonic or endergonic?
conversion of malate to oxaloacetate by malate dehydrogenase which produces another NADH
How much energy is produced per glucose?
2 ATP, 10 NADH (2 cytosolic, 8 mitochondrial), 2 FADH2 and 2 GTP ~ 30-32 ATP in total
Where and how is redox energy (NADH + FADH2) utilised?
mitochondria are the sites of oxidative phosphorylation in eukaryotes
What is oxidative phosphorylation?
defined as the process of transforming redox energy formed under aerobic conditions during glycolysis and the citric acid cycle into chemical energy in the form of ATP
How does oxidative phosphorylation drive the unfavourable formation of ATP?
redox energy is converted to an electrochemical gradient which drives the unfavourable formation of ATP
What is the first step of phosphorylation?
- transfer of electrons from NADH to complex I and/or from FADH2 to complex II
What is the second step of phosphorylation?
- flow of electrons through large multi-component inner mitochondrial membrane complexes and mobile electron transporters of the electron transport chain
What is the third step of phosphorylation?
- pumping of protons (H+) from the matrix to the intermembrane space (IMS) using the proton pumps of complex I, III, and IV as electrons flow through these complexes
What is the fourth step of phosphorylation?
- flow of protons (H+) from the IMS through the Fo component of ATP Synthase back into the matrix resulting in the rotation of the Fo component and the ɣ subunit of F1 and the synthesis of ATP from ADP and Pi by the F1 component
What creates the proton gradient that is used to drive ATP synthesis?
flow of electron through complexes in the inner mitochondrial membrane and the subsequent pumping of protons from the matrix into the intermembrane space (IMS)
How many H+ ions are pumped across complex I? How does this occur?
4 H+ ions
NADH + H+ donate 2 electrons which results in a series of events that end in the reduction of coenzyme Q (movement of electrons)
What is Coenzyme Q?
a lipophilic IMS dwelling mobile electron carrier that transfers electrons from complex I and II to complex III
What is complex II known as? Is it a H+ pump?
also known as succinate dehydrogenase from the TCA cycle
complex II is not a H+ pump (generates ubiquinol)
How many H+ ions are pumped across complex III? How does this occur?
4 H+ ions
receives ubiquinol from complex I and II
uses the electrons from ubiquinol for proton pump action
What is Cytochrome c?
a small soluble protein the resides in the IMS that accepts electrons from complex III and donates them to complex IV
How many H+ ions are pumped across complex III? How does this occur?
4 H+ ions
electrons on cytochrome c generates proton pump action
What is the electron transport chain?
flow of electrons through complexes in the inner mitochondrial membrane and the subsequent pumping of protons from the matrix into the IMS creates a proton gradient that is used to drive ATP synthesis
How does mitochondrial ATP synthase use the H+ gradient?
uses H+ gradient to drive the unfavourable synthesis of ATP from ADP + Pi -> ATP synthesis results from the rotational catalysis mechanism
What is the structure of ATP synthase?
comprised of a Fo (stalk) and F1 (head) component
Fo spans the inner mitochondrial membrane and is comprised of the a, b and c subunit, subunits in mammals
F1 is located on the matrix side of the inner membrane and is comprised of α, β, ɣ, σ, ε subunits
How many binding sites does the F1 component have?
three nonequivalent adenine nucleotide binding sites, one for each a/B pair
one site is in the B-ATP conformation, which binds ATP tightly, a second is in the B-ADP conformation which binds ADP + Pi and a third is in the B-empty conformation
the proton motive force causes rotation of the γ subunit (green) as H+ is pumped through the Fo component.
How many protons are required per ATP?
in mammals 8 protons are required to turn the ATP
synthase through one complete cycle (only 8c subunits)
so, estimated ≈4 protons are required synthesize 1 ATP
Why much ATP is yielded per NADH and FADH2?
- 5 ATP per NADH
1. 5 ATP per FADH2
Why does FADH2 produce less ATP than NADH?
because FADH2 does not pass through complex I
Can oxidative phosphorylation occur without the Krebs cycle and vice versa?
no, these processes are not able to occur without each other
Oxidative phosphorylation seems a lot of effort. Why don’t we just use glycolysis? What is the advantage?
oxidative phosphorylation produces a lot more ATP