Energy II: Acetyl CoA, Mitochondria and Oxygen

Question 1

What is aerobic respiration?

Answer 1

Occurs in the presence of oxygen
Yields more ATP
Requires the TCA cycle and oxidative phosphorylation
Takes place in the mitochondria

Question 2

What is the Citric Acid cycle?

Answer 2

A series of reactions, a cycle, that starts when pyruvate is converted to Acetyl CoA with the byproducts being NADH and CO2
The entry point for the breakdown of fatty acids and proteins
Takes place in the mitochondrial matrix
ATP is not produced in the citric acid cycle

Question 3

How is the entry regulated into the TCA cycle?

Answer 3

Formation of acetyl CoA from pyruvate is irreversible
This commits the glucose carbon skeleton to either oxidation to CO2 and energy production or fatty acid synthesis
The enzyme involved is pyruvate dehydrogenase
Inhibited by NADH and acetyl CoA
Also regulated through phosphorylation by a kinase and a phosphatase
PD phosphatase turns inactive pyruvate dehydrogenase into active
PD kinase turns the active into the inactive form
In muscle, pyruvate dehydrogenase phosphatase is stimulated by Ca2+
In the liver, adrenaline increases Ca2+ through the activation of alpha adrenergic receptors and IP3
In liver and adipose tissue, insulin (which signifies the fed state) stimulates the phosphatase which funnels glucose to fatty acid synthesis

Question 4

Recall the TCA cycle

Answer 4

Pyruvate is converted to acetyl CoA catalysed by pyruvate dehydrogenase
Acetyl CoA reacts with oxaloacetate to form Citrate (6C) catalysed by citrate synthase
Citrate is converted to Isocitrate (6C)
Isocitrate is converted to alpha-ketoglutarate (5C), catalysed by isocitrate dehydrogenase and releases NADH and CO2
Alpha-ketoglutarate is converted to succinyl CoA (4C), catalysed by alpha-ketoglutarate dehydrogenase and releases NADH and CO2
Succinyl CoA is converted to succinate (4C) which releases GTP
Succinate is converted to Fumarate (4C) releasing FADH2
Fumarate is converted to Malate (4C)
Malate is converted to oxaloacetate (4C) releasing NADH

Question 5

What is Beriberi?

Answer 5

Beriberi is a deficiency in thiamine (Vit B1)
Common where rice is a staple
Characterised by cardiac and neurological symptoms
Thiamine is a prosthetic group pyruvate and alpha-ketoglutarate dehydrogenase
Neurological problems are common as glucose is the primary source of energy

Question 6

How does the electron transport chain work?

Answer 6

Involves the removal of hydrogen atoms from oxidisable substrates notably NADH and FADH2
Hydrogen atoms enter the ETC and each is split to Gove an electron and a proton
The electron passes through a series of enzymes called cytochromes and finally reacts with molecular oxygen
Hydrogen ions are pumped across the IMM which forms an electrochemical gradient
This gradient, known as proton motive force is used to synthesise ATP with the aid of ATP synthase
Oxidative phosphorylation and ATP synthesis are normally tightly linked
Electron transport is linked to the need for ATP
Regulated uncoupling leads to the generation of heat

Question 7

What is brown fat?

Answer 7

Brown fat is fat with a ton of mitochondria which contain chromatin (therefore darker in colour than white fat)
Largely distributed around the shoulders and neck of newborns
used to generate heat as they have nit yet developed the shivering reflex
In brown fat in the inter-membrane space they express a protein called uncoupling protein I or UCP-1
This is a means of diverting the flow of protons away from the generation of ATP through to the generation of heat
Adults still retain some brown fat activity

Question 8

What are OXPHOS diseases?

Answer 8

Common degenerative diseases
Caused by mutations in genes encoding proteins of ETC
Symptoms include fatigue, epilepsy and dementia
Dependent on the mutation, symptoms may be evident near birth to early adulthood
Metabolic consequence can be congenital lactic acidosis