Energy Metabolism

Question 1

How do cells obtain energy?

Answer 1

Cells can get energy from nutrients or fuels such as carbohydrates, Proteins and lipids

•Nutrients undergo a variety of biochemical reactions, known collectively as metabolism.

Question 2

What are the different metabolic processes?

Answer 2

Anabolic processes- create larger molecules. Require energy. Example: bonding of amino acids to make proteins

Catabolic processes- larger molecules are broken down to smaller ones. Release energy . Example: glucose breakdown

Question 3

What is the currency of metabolic energy?

Answer 3

ATP

ATP is a high-energy molecule composed of adenine (purine base), ribose, and three phosphate groups

Question 4

Describe the reaction of the hydrolysis of ATP to ADP

Answer 4

Reaction is energetically favourable:
Negative Gibbs free energy (Delta G)

Question 5

How is energy utilised and produced in the ATP-ADP cycle?

Answer 5

Energy produced by metabolic processes (respiration)

Energy utilised in metabolic processes

Question 6

How do cells generate energy from nutrients?

Answer 6

Glucose metabolism:
Glycolysis
Krebs cycle
Oxidative phosphorylation

Question 7

What is glycolysis?

Answer 7

Glycolysis- anaerobic break down of glucose to pyruvate. Small amount of ATP generated by substrate level phosphorylation

Question 8

What is the krebs cell?

Answer 8

Krebs’ Cycle- oxidation of Acetyl CoA to CO. generates coenzymes: NADH and FADH2

Question 9

What is oxidative phosphorylation?

Answer 9

Oxidative phosphorylation- transduction of energy derived from fuel oxidation to high energy phosphate. Generates large amounts of ATP

Question 10

Where does glycolysis occur?

Answer 10

Occurs in cytosol under anaerobic conditions

Question 11

Why does glycolysis occur?

Answer 11

•Emergency energy producing pathway when oxygen is limiting
RBCs and exercising skeletal muscle

•Generates precursors for biosynthesis
G-6-P converted to
ribose-5-P (nucleotides) via pentose phosphate pathway
G-1-P for glycogen synthesis

•Pyruvate
•transaminated to alanine
substrate for fatty acid synthesis

•Glycerol-3-P is backbone of triglycerides

Question 12

How is glycolysis regulated?

Answer 12

•Allosteric
Binds to a non-catalytic site
Conformational change
↑s or ↓ affinity for the substrate

•Hormonal ( insulin & Glucagon)
↑s or ↓ gene expression of the enzyme
Indirect route- through affecting regulatory molecules ( usually kinases or phosphatases)
↑s or ↓ enzyme activity

Glycolytic enzymes are sensitive to the cell’s energy levels

Question 13

Give examples of regulators of glycolysis

Answer 13

• PFK is regulated by ATP, an ADP derivative called adenosine monophosphate (AMP), citrate ad Fructose 2, 6 bisphosphate

•ATP: is an inhibitor of PFK1

•AMP: is an activator of PFK-1. When ATP is used up, ADP accumulates and is converted to AMP by Adenylate kinase reaction to generate ATP. 2ADP = ATP + AMP

Increasing levels of AMP relieves the inhibition of PFK-1 by ATP

•Citrate: the first product of the kreb’s cycle also acts allosterically inhibit PFK-1. Increase citrate levels is a signal that the cycle does not need more fuel.

•Fructose-2,6-bisphosphate: generated from Fructose-6-phosphate is the most important allosteric activator of PFK1. Mediates effect of insulin and glucagon

Question 14

What happens to pyruvate under anaerobic conditions?

Answer 14

Anaerobic conditions
•Lactate formation catalysed by lactate dehydrogenase
• Regeneration on NAD+

Question 15

What happens to pyruvate under aerobic conditions?

Answer 15

Aerobic conditions
•Enters mitochondria converted to Acetyl CoA and CO2 by Pyruvate Dehydrogenase.
•Acetyl CoA can enter TCA cycle for more energy production

Question 16

What is the equation for pyruvate under anaerobic conditions?

Answer 16

glucose + 2ADP + 2Pi →
2lactate + 2ATP + 2H2O + 2H+

Question 17

What is the equation for pyruvate under aerobic conditions?

Answer 17

pyruvate + CoA + NAD+ —>
acetyl-CoA + CO2 + NADH + H+

Catalysed by Pyruvate dehydrogenase, a multienzyme complex within mitochondrial matrix
•Inhibited by high concentrations acetyl-CoA and NADH
•Inactivated by phosphorylation
•Activated by phosphate removal

Question 18

Where does the krebs cycle occur?

Answer 18

Occurs in mitochondrial matrix, aerobic conditions

Question 19

Why does the krebs cycle occur?

Answer 19

Generates lots of energy (ATP)

Provides final common pathway for oxidation of carbohydrates, fat & protein via acetal CoA

Produces intermediates for other metabolic pathways

Question 20

Provide an overview of the Krebs cycle

Answer 20

•Acetyl CoA condenses oxaloacetate with acetate
•Oxaloacetate regenerated in the Krebs’ cycle

Question 21

What is the overall reaction for the krebs cycle?

Answer 21

acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O —>
2 CO2 + 3 NADH + FADH2 + GTP + 3 H+ + CoA

Question 22

What is the net energy gain in the krebs cycle?

Answer 22

6 NADH
2 FADH
2 ATP

Question 23

Explain the regulation of pyruvate dehydrogenase

Answer 23

•Conversion of pyruvate is converted to acetyl CoA. Is an irreversible and tightly regulated to control how much fuels enteres the kreb’s cycle

•ATP and NADH negatively inhibit pyruvate dehydrogenase. ADP activates it

•Pyruvate dehydrogenase is also activate d by its substrate, pyruvate, and inhibited by its product, acetyl CoA. This ensures that acetyl CoA is made only when it’s needed

Question 24

Explain the regulation of citrate synthase

Answer 24

•ATP and NADH allosterically inhibit citrate synthase. Reduce affinity of citrate synthase for its substrates

•Succinyl Co-A competitively inhibits citrate synthase

•^ citrate inhibition citrate synthase, reduces speed of cycle

Question 25

Explain the regulation of Isocitrate DH?

Answer 25

•A key rate limiting enzyme of Krebs’ Cycle

•In states of increased oxidative phosphorylation demands, the rate of the Krebs’ Cycle reactions is increased

•However, limited by product inhibition of citrate synthase

•Isocitrate dehydrogenase activation leads to a decrease in citrate

•Citrate synthase reaction rate increased

Question 26

Explain the regulation of a-ketoglutarate DH

Answer 26

•Inhibited by its products NADH and succinyl-CoA

•Also inhibited by GTP, ATP, and reactive oxygen species (ROS)

•ROS are also produced by α-ketoglutarate DH

•Activated by Ca2+ —> may be useful in generating ATP during intense muscle exercise

Question 27

Where does oxidative phosphorylation occur?

Answer 27

Occurs in the inner mitochondrial membranes, aerobic conditions

Question 28

Why does oxidative phosphorylation happen?

Answer 28

•Releases the majority of energy during cellular respiration

•Reduced NADH or FADH2 from glycolysis and Kreb’s cycle are oxidised and their electrons passed to components of the electron transport chain (ETC). These are a series of carriers embedded in the inner mitochondrial membrane. The final electron acceptor is O2.

•Energy released is trapped to generate ATP

Question 29

Provide an overview of oxidative phosphorylation

Answer 29

•Components of ETC accept electrons (reduced) and pass them on (oxidised)

•electrons are transferred to their final electron acceptor = oxygen

•The free energy is used to “power” the movement of H+ (protons) across the inner membrane
space creating a proton motive gradient

•ATP produced as protons flux in through ATP synthase

Question 30

Why does ATP release a lot of energy

Answer 30

High energy hydrogen bonds between the 3 phosphates in ATP

Question 31

Does glycolysis need oxygen to occur?

Answer 31

No, glycolysis occurs with or without oxygen