Energy Production: Carbohydrate 4 Flashcards
What is pyruvate dehydrogenase? Why is it important?
It’s an enzyme that converts pyruvate into acetyl CoA.
What is essential for the conversion from pyruvate to acetyl CoA?
Pyruvate + CoA + NAD+ -> Acetyl CoA + CO2 + NADH + H+
Where does the reaction of pyruvate to acetyl CoA take place?
Mitochondrial matrix
Why is this an important step?
Because it is irreversible
What is a dietary factor that is important for this reaction?
B-vitamins are used as cofactors. So a Vitamin B1 deficiency means that there is a build up of pyruvate.
What are some factors that stimulate pyruvate dehydrogenase?
Pyruvate CoASH NAD+ ADP and AMP Insulin
What are some factors that inhibit pyruvate dehydrogenase?
Acetyl CoA NADH ATP Citrate Glucagon?
What are the committing steps in TCA cycle?
Isocitrate (C6) going to C5. Here NAD+ goes to NADH and CO2 is also released.
Also C5 to C4 which is the next step. Here CoA is inserted but NAD+ goes to NADH and CO2 is released.
What makes isocitrate to C5 and C5 to C4 be irreversible steps?
The release of CO2.
What are the products of the TCA that we are interested in that are produced by a glucose molecule?
6 NADH
2 FADH2
2 GTP
But only half of those products are produced in the TCA at one time. How can this be the case?
Because in glycolysis glucose goes to two pyruvates. This mean that 2 acetyl CoA are formed and the TCA cycle is done twice.
Where does regulation occur in the TCA? What enzymes are affected?
In the committing steps aka Isocitrate to C5 and C5 to C4. Isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase respectively are affected.
What inhibits or stimulates isocitrate dehydrogenase?
Inhibits:
ATP and NADH
Stimulates:
NAD+, ADP and AMP
What inhibits or stimulates alpha-ketoglutarate dehydrogenase?
Stimulates: NAD+ and maybe CoA Inhibits: NADH ATP Succinyl-CoA
TCA is not only used to make a lot of reducing powers for energy. What else is it used for?
TCA supplies biosynthesis. Citrate -> Fatty acids alpha-ketoglutarate -> amino acids Succinate -> amino acids and Haem Malate -> amino acids Oxaloacetate -> amino acids and glucose
Give a brief summary of TCA
It’s a catabolic pathway for sugars, fatty acids, ketone bodies, amino acids and alcohol that happens in the mitochondria.
It releases CO2 by breaking carbon bonds.
Produces 6 NADH, 2 FADH2 and 2 GTP.
It also produces precursors for biosynthesis so not only catabolism but also anabolism.
It does not function in absence of O2.
What is stage 4 in catabolism?
This is the electron transports chain and oxidative phosphorylation.
Where and what happens in electron transport chain and oxidative phosphorylation?
It happens in the mitochondrial matrix, inner mitochondrial membrane and inter membrane space.
Here NADH and FADH2 are re-oxidised.
It requires O2 to work.
Produces a large amount of ATP.
Briefly explain the electron transport chain.
NADH + H+ donates 2H+ and 2 electrons.
The donation of 2H+ happens three times. Only 2 electrons are used per cycle. The electrons go through 3 proton translocating complexes which makes the 6H+ to be transported from the mitochondrial matrix to the inter membrane space. The low energy 2 electrons then react with 2H+ and oxygen to form H2O.
Why would protons be pumped out into the intermembrane space?
Because it sets up a concentration gradient of H+ called the proton motive force. This makes H+ to be transported into the matrix again via ATP synthase which makes ADP and inorganic phosphate to make ATP. This is the basis of ATP synthesis and called oxidative phosphorylation.
How can oxidative phosphorylation be regulated?
By an increased concentration in ATP. This stops ADP and inorganic phosphate to convert into ATP. This means that H+ stops being transported into matrix again and there is a build up of H+ in the intermembrane space. This causes the electron transport chain to stop pumping out H+ into the intermembrane space as well.
What gives most moles of ATP, NADH or FADH2?
NADH.
How many moles of ATP do 2 moles of NADH give?
2 moles give 5 moles of ATP. Ideally it would give 6.
How many moles of ATP do 2 moles of FADH2 give?
2 moles give 3 moles of ATP. Ideally it would give 4.
What inhibits (not regulates) oxidative phosphorylation?
Cyanide (CN-) prevents acceptance of electrons by O2. Also carbon monoxide. This is because Cyanide binds with higher affinity.
Uncouplers as well.
Oxidative phosphorylation diseases
What are uncouplers? Give examples. How does it work and why is it important in oxidative phosphorylation?
Uncouplers are fatty acids, dinitrophenol and dinitrocresol.
They increase the permeability of the inner mitochondrial membrane for H+.
Why do we not want an increased permeability of the inner mitochondrial membrane for H+?
Because that means that H+ can cross the inner mitochondrial membrane from the intermembrane space to the matrix without the use of ATP synthase. This means that there will be less ATP synthesis.
Where are uncouplers used as a favourable pathway?
In brown adipose tissue it is used to generate heat instead of ATP.
Briefly explain the pathway in brown adipose tissue.
In the response to cold noradrenaline activates Lipase which releases fatty acids from triacylglycerol.
Fatty acid oxidation occurs which produces NADH and FADH2 to be fed into electron transport chain.
Fatty acids activate UCP1 which is an uncoupler.
UCP1 increases the permeability and transports H+ back into mitochondria once again. This means less that ATP synthesis does not happen but instead energy is released as heat.
