Energy II: Acetyl CoA, Mitochondria and Oxygen

Question 1

Where does aerobic respiration occur in?

Answer 1

Mitochondria.

Question 2

What properties of the mitochondria allows for aerobic respiration to take place in?

Answer 2

The inner membrane is very impermeable and the outer membrane is more permeable which means a gradient, something which enables ATP to be produced.

Question 3

Where does the citric acid cycle take place?

Answer 3

In the matrix of the mitochondria.

Question 4

What happens in the citric acid?

Answer 4

A molecule of pyruvate is decarboxylated and turned into acetyl CoA, producing CO2 and NADH as other products.
The acetyl CoA then reacts with oxaloacetate to form citrate which reacts further to produce CO2, NADH, FADH2 and GTP.

Question 5

What regulates entry of the pyruvate molecule into the citric acid cycle?

Answer 5

The enzyme pyruvate dehydrogenase.

Question 6

What is pyruvate dehydrogenase?

Answer 6

A very large, multi-complex protein which can be inhibited by its products (NADH and Acetyl CoA). It is also regulated through phosphorylation- the phosphorylated state requires a kinase and phosphatase- which activities are associated with the enzyme; it can be turned on and off by enzyme activity where-by phosphorylation turns it off, and the release of Ca2+ in during muscle stimulation can turn the enzyme on again.

Question 7

How can the release of more Ca2+ ion occur in the liver?

Answer 7

The liver can release the hormone adrenaline which activates a-adrenergic receptors and IP3, which causes Ca2+ ions to be released. This results in the pyruvate dehydrogenase to be turned on.

Question 8

How can the release of insulin affect pyruvate dehydrogenase?

Answer 8

In the liver and adipose tissue, insulin can be released which stimulates phosphatase which funnels glucose to fatty acid synthesis and also results in pyruvate dehydrogenase to reduce in activity.

Question 9

What are the enzymes involved in the citric acid cycle?

Answer 9

• Citrate synthase: used to convert acetyl CoA and oxaloacetate into citrate.
• Isocitrate dehydrogenase: used to convert isocitrate into a-ketoglutarate.
• a-ketoglutarate dehydrogenase: used to convert a-ketoglutarate into succinyl CoA.

Question 10

What are the negative regulators of the citric acid cycle?

Answer 10

NADH, ATP and Acetyl CoA.

Question 11

What is BeriBeri and how does the disease affect the citric acid cycle?

Answer 11

• A deficiency due to thiamine – Vitamin B1. Usually occurs where rice is a staple food.
• The enzymes in TCA cycle are compromised especially pyruvate dehydrogenase and α-ketoglutarate dehydrogenase – both require Vitamin B1. Deficiency means the TCA is compromised as well as generation of ATP. Most important in neurological tissues (as well as cardiac) – they generate most of ATP from glucose and require large amounts of ATP and oxygen and so neurological disorders is common symptoms.

Question 12

Where does the NADH and FADH2 go after the citric acid cycle?

Answer 12

It goes to the electron transport chain which is used to produce ATP via oxidative phosphorylation.

Question 13

LOOK AT NOTES TO SEE DIAGRAM FOR ETC.

Answer 13

LOOK AT NOTES TO SEE DIAGRAM FOR ETC.

Question 14

What is the overview of the ETC?

Answer 14

• Involves the removal of hydrogen atoms from oxidizable substrates notably NADH and succinate.
• Hydrogen atoms enter the ETC and each is split to give an electron and a proton.
• The electron passes through a series of enzymes called cytochromes and finally reacts with molecular oxygen.

Question 15

How is ATP formed in the ETC?

Answer 15

ATP is formed from the electrochemical gradient that was created with the protons. The H+ ions that were pumped across the membrane will go through the membrane via ATP synthase following the concentration gradient that was created, and through the action of the protons moving through the channel protein, it generates energy (chemiosmosis).
This energy that is generated is used to react ADP and Pi together to form ATP.

Question 16

What are the reasons that the generation of the gradient is uncoupled from the generation of ATP, the gradient is being used for something else?

Answer 16

It can either be physiological or pathological.

Question 17

What is the physiological reason for the gradient to be uncoupled from the production of ATP?

Answer 17

In newborn infants, there are two sets of fat- Brown and White fat.
A newborn baby does not know how to shiver so it need to be able to generate heat through another process. Therefore brown (very rich in mitochondria so brown) fat is distributed near the shoulder and along the back. This fat has an uncoupling protein expressed in them – this splits the gradient from the synthesis of ATP. As the protons fall back down the gradient rather than producing ATP they produce large amounts of heat. This allows the infant to maintain their body temperature.

Question 18

What is the pathological reason for the gradient to be uncoupled from the production of ATP?

Answer 18

Number of diseases called OXPHOS Diseases. These are common degenerative disease that target tissue sensitive to energy deprivation and who are reliant on oxidative phosphorylation for their energy needs. It caused by mutations in genes encoding proteins of the Electron transport chain and lead to a number of symptoms including fatigue, epilepsy and dementia.
Depending on the mutation, the symptoms may be evident near birth to early adulthood. Metabolic consequence can be congenital lactic acidosis.

Question 19

What regulates the electron transport chain?

Answer 19

• Governed by the need for ATP- when a cell requires ATP, the ETC is stimulated.
• Electron transport tightly coupled to phosphorylation i.e. ADP to ATP- some exceptions though.
• Regulated uncoupling leads to the generation of heat.