Energy I: Metabolism, ATP, Glycolysis

Question 1

Why do we need energy?

Answer 1

We need energy to carry out the processes of life including:
1.	Synthesis of new molecules.
2.	Establishing ion gradients.
3.	Keeping warm.
Mechanical work.

Question 2

Define catabolism.

Answer 2

The breakdown of complex molecules to release energy of carry out mechanical work.

Question 3

Define anabolism

Answer 3

The synthesis of new molecules from less complex components.

Question 4

Why study metabolism?

Answer 4

• Metabolic basis of disease. – e.g. diabetets, atherosclerosis gall stones.
1. Diseased state changes the way the body uses food. – e.g. in cancer.
2. To understand a disease – may need to know how the body normally deals with nutrients.
Can use changes in metabolites to aid diagnosis and to follow treatment.

Question 5

What makes metabolic pathways all link together?

Answer 5

Often the product of one pathway is the substrate of another pathway.
Also, metabolic pathways exist to maintain a physiological state.

Question 6

What is ATP in terms of energy/energy storage?

Answer 6

ATP is a body’s energy provision. It can act as both an acceptor and donator of energy. It acts as a short-term reservoir of energy.

Question 7

What evidence is there that ATP is re-synthesised from ADP and Pi?

Answer 7

The body only has 100g of ATP, which is not enough for the body to use during exercise or even at rest. So ATP must be resynthesized to meet these demands. This is largely done through oxidative phosphorylation (in the mitochondria).

Question 8

What does Phospho-fructokinase do? and what is it stimulated and inhibited by?

Answer 8

• converts fructose-6-phosphate
• inhibited by ATP, citrate and H+ (acids)
• stimulated by F26BP and AMP

Question 9

Describe the process of glycolysis. (glucose –> pyruvate).

Answer 9

1) Glucose is phosphorylated by Hexokinase to G6P (using ATP, making ADP).
2) G6P is them converted to Fructose-6-phosphate.
3) Fructose-6-phosphate is then phosphorylated by Phospho-fructokinase (PFK) to Fructose 1,6 bisphosphate (using ATP, making ADP).
4) Fructose 1,6 bisphosphate is then converted to two C3 molecules, Dihydroxy acetone phosphate and GALP (Glyceraldehyde-3-phosphate). These 2 molecules are kept in equilibrium, and it favours GALP.
5) GALP is then converted to phosphoenol pyruvate (using NAD+ and Pi, and ADP, making NADH and ATP).
6) Phosphoenol pyruvate is then converted by Pyruvate Kinase to pyruvate (using ADP, making ATP).

Question 10

What are the 3 enzymes involved in glycolysis?

Answer 10

1) Hexokinase
2) Phospho-fructokinase
3) Pyruvate Kinase

Question 11

What does Hexokinase do? and what is it inhibied by?

Answer 11

• converts glucose to G6P

- inhibited by G6P

Question 12

What does the inhibition of Phosphofructokinase lead to?

Answer 12

Inhibition of PFK leads to the inhibition of G6P.

Question 13

How many molecules of pyruvate formed per glucose molecule?

Answer 13

2

Question 14

Summarise the balance of reactants and products in glycolysis. (glucose, pyruvate, ATP, NAD+, NADH, ADP+Pi

Answer 14

Reactants:
1 Glucose
2 NAD
2 ADP+Pi

Products:
2 Pyruvate
2 NADH
2 ATP

Question 15

What is the reaction that produces something that signals low energy state?
And what enzyme catalyses the reaction?

Answer 15

ADP + ADP -> ATP + AMP

by enzyme adenylate kinase

Question 16

Why is ADP not the signal molecule for low energy state?

Answer 16

As 2ADP gives ATP + AMP. Therefore, AMP is a better indicator of energy state.

Question 17

What is relevant about the liver, in terms of glycolysis?

Answer 17

There are two enzymes that convert glucose to G6P; Hexokinase and Glucokinase. Hexokinase is found in (pretty much) all cells in the body, and Glucokinase is found mainly in hepatic cells (in the liver). Glucokinase works at higher glucose levels, and isn’t inhibited by G6P.

Question 18

Why must glycolysis be regulated in muscle to meet the need for ATP?

Answer 18

Because it is important for muscle to protect them from excessive lactate production during anaerobic respiration.

Question 19

What does pyruvate kinase do and what is it inhibited by?

Answer 19

• converts phosphoenol pyruvate to pyruvate

- inhibited by ATP

Question 20

What regulates entry into the citric acid cycle?

Answer 20

The 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.

Pyruvate Dehydrogenase is regulated through phosphorylation. Inhibited by phosphorylation (using ATP?)
• In muscles, Pyruvate Dehydrogenase is activated again via the action of a phosphatase; this enzyme is stimulated by Ca2+ (this increases CoA production).
• In the liver, adrenalin increases calcium through the activation of α-adrenergic receptors and IP3.
• In the liver and adipose tissue, insulin (which signifies the feed state) stimulates the phosphatase, which funnels glucose to Fatty Acid synthesis
Build up of NADH and acetyl CoA inform the enzyme that energy needs of the cell are being met, or that fatty acids are been broken down to produce NADH and Aceytl CoA. This has the effect of sparing glucose.

Question 21

What does inhibition of isocitrate dehydrogenase and alpha-ketogluterate dehydrogenase lead to?

Answer 21

Build of citrate.

Question 22

What happens when citrate is transported out of the mitochondria?

Answer 22

• It inhibits PFK, which stops glycolysis.

It also acts as a source of acetyl CoA for Fatty Acid synthesis.

Question 23

Describe BeriBeri

Answer 23

• It’s a disease in which the body has a deficiency in thiamine (Vit B1).
• Thiamine is a prosthetic group for pyruvate and α-ketoglutarate dehydrogenase.
o Therefore, enzymes are compromised leading to the TCA being compromised and so a decrease in ATP production.
• It’s characterised by cardiac and neurological symptoms (impairment of nerves and heart).
It’s common where rice is a staple. Neurological disorders are common as glucose is a primary source of energy.

Question 24

What happens to the NADH and FADH2 produced?

Answer 24

Oxidative phosphorylation.
1. Removal of hydrogen atoms from oxidisable substrates, NADH and FADH2 (and succinate?).
2. H atoms enter ETC and each is split to give an electron and a proton.
3. The electron passes through a series of enzymes called cytochromes ad finally reacts with molecular oxygen.
Water is formed as oxygen receives the electrons from the 4th protein complex and combines with protons on the inside of the cell.

Question 25

What happens after hydrogen is pumped across the Intermembrane?

Answer 25

• Hydrogen atom is pumped acorss the IMM which forms a pH gradient transmembrane poteintial (proton motive force).
• This is coupled to ATPsynthase.
• Protons pass through ATPsynthase as they move back into the matrix.
This movement generates enough energy for it to combine ADP and Pi into ATP.

Question 26

How many ATP is produced per NADH and FADH2?

Answer 26

NADH forms 3 ATP.

FADH2 forms 2 ATP.

Question 27

Where is brown fat and white fat found?

Answer 27

Brown fat is found in newborns and white fat is found in adult tissues.
Morphology differs b/w white and brown fat

Question 28

Why do newborn babies need brown fat?

Answer 28

• New born babies cannot shiver, so they have brown fat (brown due to the high levels of mitochondria).
• High levels of brown fat in newborns provides an alternative way of regulating heat, to protect them from hypothermia.
• The brown fat is distributed around the shoulders and down the back. As they grow, the amount of brown fat they have decreases.
• Mitochondria express uncoupling protein – splits gradients formed from ATP synthesis. – generate heat instead of ATP, after H+ move down their concentration gradient.

Question 29

What are Oxphos diseases?

Answer 29

• They are common degenerative diseases. – target tissues sensitive to energy deprivation – reliant to oxidative phosphorylation.
• They’re caused by mutations in genes encoding proteins of the ETC.
• They lead to a number of symptoms, such as fatigue, epilepsy, dementia, etc.
• It’s dependant on the mutation, and symptoms may be evident near birth to early adulthood.
• One metabolic consequence can be Congenital Lactic Acidosis (CLA, a rare disease that affects the cells ability to use energy and causes a build up of lactic acid).
Neurological problems

Question 30

How is the electron transport chain regulated?

Answer 30

• Governed by the need for ATP.
• Electron transport tightly coupled to phosphorylation (requirement of ATP?) i.e. ADP to ATP
Regulated uncoupling leads to generation of heat.