Introduction to Metabolism

Question 1

What is metabolism?

Answer 1

Means by which organisms extract energy from their environment and use this to synthesize large molecules

Question 2

Why is metabolism clinically important in regards to health?

Answer 2

Good health is absolutely dependent on well-balanced metabolism

Question 3

Why is it clinically important to know about metabolism?

Answer 3

Many disorders involve changes in the balance of metabolic activities
E.g. Diabetes, obesity or vitamin deficiencies
Many clinical biochemical tests are designed to investigate aspects of metabolic function
Understanding the molecular mechanisms underlying these conditions is essential

Question 4

What is the oxygen requirement of a resting human?

Answer 4

approx ml 350 O2/min

1.75 litres/ 5 mins

Question 5

By what factor does oxygen consumption increase when a person is exercising?

Answer 5

Up to roughly 5x

Question 6

What is oxygen used for?

Answer 6

To oxidize substrates and produce energy for the body􏰀s needs

Question 7

Define oxidation and reduction

Answer 7

Oxidation = Addition of oxygen to molecules
-Can also be considered as removal of electrons from molecules

Reduction = removal of oxygen from molecules -Can also be considered as addition of electrons

Question 8

Define anabolism and catabolism

Answer 8

Anabolism: Process by which large molecules are built from smaller ones
-Requires an energy input
Catabolism: Breakdown of large molecules to smaller ones -Releases energy

Question 9

What is DeltaG

Answer 9

Chemical reactions either absorb or release energy

This is expressed as the change in free energy = DeltaG

Question 10

How does one figure out DeltaG?

Answer 10

For the reaction A + B C + D

DeltaG = DeltaGo + RT loge ([C][D])/([A][B])

Where
DeltaG = Free energy change for the reaction with reactants at the concentrations given
DeltaGo = Standard free energy change (when all reactants are present at a concentration of 1.0 M)
R = Gas constant
T = Absolute temperature

Question 11

When can a reaction occur spontaneously(without energy input)?

Answer 11

if the free energy change (DeltaG) is negative

Question 12

What determines the reaction rate of a spontaneous reaction?

Answer 12

Free energy of activation

The reaction rate depends on the energy hump that must be climbed for the reaction to occur. This is called the free energy of activation (DeltaG*) which is unrelated to DeltaG

Question 13

What is normally involved between the substrate and the product in a reaction?

Answer 13

An intermediate (transitional) state

Question 14

What may increase the reaction rate?

Answer 14

A catalyst amongst other things

Question 15

How might a spontaneous reaction take place with a positive deltaG?

Answer 15

coupled reactions can take place without energy input as long as there is a overall negative change in free energy (DeltaG) between the starting materials and the final product(s) of the reaction sequence.

Question 16

What is the purpose of ATP in metabolism

Answer 16

To allow energy-requiring processes to occur, the energy released during catabolism needs to be captured and stored in a form that is usable
ATP is that form (= currency)

Question 17

What is ATP?

Answer 17

Inorganic phosphate = PO>4^3- =Pi
Phosphate groups (PO>4^3-) are sometimes shown as –P just to make structures look simpler (e.g. glucose-6-P)

Question 18

What is phosphorylation?

Answer 18

Phosphorylation (phosphorylate) = adding a phosphate group to a molecule (e.g. converting ADP to ATP)

Question 19

Discuss the high energy bonds of ATP

Answer 19

A large amount of energy is released when ATP is hydrolysed to ADP + inorganic phosphate (Pi)
= approx -7 to -12 kcal/mol
Hydrolysis of ATP is used to drive energy-requiring processes (e.g. anabolism, movement and ion transport)

Question 20

What is the ATP turnover in a resting human and a human partaking in strenuous exercise?

Answer 20

Resting human consumes approx 50 kg (approx 110lb = 71⁄2 stone) of ATP in 24 hrs (approx 175 g/5 mins)
-In strenuous exercise can be as much as 0.5 kg/min (2.5 kg/5 mins)

Question 21

What is ATP used for in the body? (other than for phosphorylation)

Answer 21

• Body movement (via muscular contraction)
• Neuronal activity (CNS & peripheral nerve activity)
• Cellular movements (via cytoskeleton)
• Active transport
• Synthesis of large molecules

Question 22

What process generates ATP?

Answer 22

The citric acid (krebbs) cycle and anaerobic respiration

Question 23

How can regulation of the metabolism be achieved?

Answer 23

1. Changes in amounts of substrates and products of pathways (e.g. ratio of ATP to ADP + Pi affects energy producing and energy-requiring pathways in opposite ways)
2. Changes in amounts of key enzymes
3. Changes in activity of key enzymes

Question 24

What changes in activity of key enzymes might help bring about the regulation of the metabolism?

Answer 24

• Allosteric changes
• Effects of substrate and downstream products on enzyme activity
• Covalent modification of enzymes (e.g. phosphorylation)

Question 25

What are some hormones that have a major regulatory effect on some enzymes?

Answer 25

insulin, glucagon and adrenaline

Question 26

When is ATP formed?

Answer 26

ATP is formed when fuel molecules are oxidized

Question 27

What molecules are interconvertible with ATP?

Answer 27

ATP, ADP and AMP are interconvertible under appropriate conditions

Question 28

What molecules may serve a similar role to ATP?

Answer 28

In some cases other nucleotides such as guanosine diphosphate (GDP) and guanosine triphosphate (GTP) can serve a similar role to those of ADP and ATP