CELL Energy II: Acetyl CoA, Mitochondria, Oxygen Flashcards
in the absense of o2, we can make lactate. Why is this pathway inefficient?
what is the purpose of this pathway? (2)
advantage of TCA and oxidative phosphorylation?
- This is not an efficient way of generating ATP but serves a purpose in that it is quick and only requires the appropriate enzymes and substrates.
- This lecture talks about the other possible fate of pyruvate which is entering the TCA (Krebs) cycle and ultimately generating ATP through oxidative phosphorylation.
- The main advantage of this is that it produces a lot of ATP, but the disadvantage is that it requires O2.
Aerobic Respiration
what does it require? benefit? where does it take place? 2 key processes?
mitochondria structure?
where does tca cycle occur? where does oxidative phosphorylation occur?
Aerobic respiration occurs only in the presence of O2 and yields more energy in the form of ATP and requires the citric acid cycle and oxidative phosphorylation. It takes place in the mitochondria.
Mitochondrial structure is that it contains an outer mitochondrial membrane and an inner mitochondrial membrane with the intramitochondrial space in between.
On the inside is the matrix the TCA cycle occurs and on inner mitochondrial membrane is where oxidative phosphorylation occurs.
TCA cycle
what is the starting molecule?
what is pyruvate converted into? what is lost and made?
what does the molecule enter? where does this occur?
what does it react with? to become? what happens to this?
what molecyle remains the same? why?
for eevry turn of the cycle what do you generate?
so for each glucose what do you make?
Cytosolic process
Prior to this glucose is converted to two (3C) pyruvate molecules.
• From now one we’ll be referring to one cycle of citric acid cycle so one of the 2 pyruvates.
The pyruvate then undergoes a reaction to become (2C) acetyl CoA, during this reaction there is a loss of CO2 and an NADH is generated.
Acetyl-coA then enters the TCA cycle which occurs in the mitochondrial matrix and reacts with (4C) oxaloacetate to become (6C) citrate.
The amount of oxaloacetate remains the same it is continually recycled
Citrate undergoes a series of reactions resulting in the loss of 2CO2 becoming a 4C molecule.
For every turn of the cycle you generate:
• 3 NADH
• 1 FADH2
• 1 GTP molecule is formed
ATP is NOT produced in the citric acid cycle
So, for each glucose:
- 6 NADH (within)+ 2 NADH (In producing Acetyl-CoA)
- 2 FADH2
- 2 GTP
- 4 CO2 + 2CO2 (acetly-CoA)
What regulates entry into the TCA cycle?
what type of reacton is this?
what does this commit the glucose to? (2)
what enzymes does this conversion? what inhibits it? (2)
how is it inhibited?
The first point of regulation is the formation of Acetyl- CoA from pyruvate which is an irreversible reaction.
- This commits the glucose carbon skeleton to either oxidation to CO2 and energy production or fatty acid synthesis.
The enzyme that does pyruvate -> Acetyl-CoA is pyruvate dehydrogenase, importantly this enzyme is inhibited by NADH and Acetyl-CoA.
The products of the reaction, (note also inhibited by ATP which is a product of whole process), so if these both accumulate the enzyme will be inhibited.
- The enzyme is inhibited by phosphorylation (covalent modification)
What regulates entry into the TCA cycle? in muscles
what is it dependent on? why? what does it stimulate?
what does this allow muslce to link contraction with?
In muscle, pyruvate dehydrogenase is activated via the action of phosphatase, which removes the phosphorylation, this phosphatase in muscle is stimulated by Ca2+. Therefore, it is calcium dependent.
- This allows the muscle to link contraction to a process that will generate ATP.
- Ca2+ is important for contraction and ATP is needed for contraction, so increased Ca2+ will cause the contraction and enable more ATP to be supplied.
What regulates entry into the TCA cycle? in liver
what increases ca2+ conc? via what? (2)
In the liver adrenalin increases Ca2+ through the activation of α-adrenergic receptors (hormonal regulation) and IP3.
What regulates entry into the TCA cycle?
liver and adipose tissue
what hormone is active? what does it stimulate? effect?
In the liver and adipose tissue, insulin (which signifies the fed state) stimulates the phosphatase which funnels glucose to fatty acid synthesis.
• This is a similar process but is not for producing ATP rather it is for storage.
There are three more control points, and these are within the cycle
what does citrate inibit? what does this prevent the conversion of? what is the effect of this?
6c to 5c - what is the enzymes? what inhibits? (2) what stimulates?
5c to 4c? - enzyme? what is the conversion? inhibited by? (3)
what inhibits entry into TCA? (3) what stimulates entry? (2)
The first is the conversion of Acetyl-CoA -> Citrate under action of the enzyme citrate synthase. It is inhibited by citrate itself, product inhibiting enzyme that made it.
• This means in cases where there is enough ATP the Acetyl-CoA will be directed to other ways e.g. fatty acid synthesis.
Also control of isocitrate -> α-ketoglutarate, by enzyme isocitrate dehydrogenase. Inhibited by NADH, ATP. Stimulated by ADP. (6c to 5c)
Also control of α-ketoglutarate -> Succinyl CoA by α-ketoglutarate dehydrogenase.
• It is inhibited by NADH, ATP, Succinyl CoA. (5c to 4c)
- The control of entry into TCA spoken of earlier: pyruvate -> Acetyl-CoA is inhibited by NADH, ATP, Acetyl-CoA. It is stimulated by ADP and pyruvate.
Beriberi
what is it?
where is it prevalent?
what is it characterised by? (2)
what is the reason for this? what is it required for? (2)
hence effect of this? why?
Beriberi is a deficiency in thiamine (Vit B1) and is common in the far-east where rice is staple. As a disease it is characterised by cardiac and neurological symptoms.
The reason for this is that thiamine is a prosthetic group for pyruvate and α-ketoglutarate dehydrogenase i.e. thiamine is required to make these enzymes.
These enzymes are important in regulating the TCA cycle, so these enzymes will be deficient in someone with Beriberi; hence inability to generate sufficient ATP
Neurological disorders are common as glucose is the primary source of energy.
Fate of NADH and FADH2
where are they used?
what does the etc involve? how does this involve NADH and FADH2?
what enters the ETC and what happens to them? what passes through a series of enzymes? what are these called and how does energy change? what does it finally react with?
what about the other molecule? what does this generate?
NAHD - H+? ATP?
FADH2 - H+? ATP?
The NADH and FADH2 are used in the electron transport chain
The ETC involves the removal of hydrogen atoms from oxidisable substrates, notably NADH and FADH2.
- The hydrogen atoms enter the ETC and are each is split to give an electron and proton.
- The electron is passed through a series of enzymes called cytochromes from left to right, going from high energy to low energy state.
- It finally reacts with molecular oxygen
The proton is pumped across the inner mitochondrial membrane into the IMS, which generates a proton gradient (pH gradient). This gradient can be harnessed to produce ATP.
• For every NADH we get 3 ATP
• For every FADH2 we get 2 ATP
These are approximations, not always 100% efficient.
- 10 H+ are pumped out for every NADH
- 6 H+ are pumped out for every FADH2
occurs in inner mitochondrial membrane so between matrix and inner membrane space (pumped from matrix to ims via inner mitchondrial membrane)
ATP synthesis
what enzyme is involved? how does it act? where is it?
what is needed? why does this move?
o ATP synthase is a transmembrane protein which acts as a motor.
o H+ pumped out into IMS will be able to drop back down their H+/pH gradient through ATP synthase.
o As it does this and moves through it generates ATP from ADP.
Mitochondria and Heat Generation in New Born
what can neonates not do? what is the significance of this?
what do the posses more of? where is this? what does this contain a large number of?
how is neonates mitochondrai different to adults? what does this do? what does this generate instead? why?
There are instances where proton movement across IMM is no longer coupled with ATP synthesis.
Neonates do not have the ability to shiver and obviously shivering is a good way of generating heat, so a newborn who cannot generate heat will lose heat from their surface.
Neonates possess brown fat, which is predominantly around neck and shoulders. Brown fat contains a large no. of mitochondria, giving the brown fat its colour.
The mitochondria in an infant are different to adult.
One difference is they contain a protein called uncoupling protein, which uncouples the proton gradient with ATP synthesis.
Uncoupling protein is an alternative route by which H+ can move down its conc. gradient and in doing so it doesn’t generate ATP, it generates heat.
So, this is what we believe happens in order for them to generate heat, note that obviously not all their mitochondria will be have uncoupling protein, only those in brown fat tissue.
OXPHOS Diseases
symptoms? (3)
what is a metabolic conseqeunce?
These are common degenerative diseases caused by mutations in genes encoding proteins of the ETC.
This leads to several symptoms including fatigue, epilepsy and dementia.
o Depending on the mutations, symptoms may be evident near birth to early adulthood.
o A metabolic consequence can be congenital lactic acidosis.
What regulates ETC?
what is it governed by?
where are there exceptions to this?
- It is governed by the cells needed for ATP
- Electron transport is tightly coupled to the demands of the cell for energy which is tightly coupled to phosphorylation i.e. ADP -> ATP
There are exceptions -> Regulated uncoupling in tissue where uncoupling protein is expressed leads to generation of heat
