LECTURE 3

Question 1

What is one of the most energetic organs

Answer 1

The heart

Question 2

Where does energy for life come from initially?

Answer 2

For most life on earth, most energy on earth comes from the sun

Plants collect and use the suns (light) energy, then herbivores consume the plants, and carnivores/other animals consume the herbivores

In every step, heat (energy) is lost as waste - therefore the energy decreases each time, which is intrinsic to the laws of thermodynamics

Question 3

Describe anabolic vs catabolic processes

Answer 3

Anabolic Processes are those that cause building of molecules

Catabolic processes are those that break down molecules

Question 4

How do anabolic and catabolic processes relate to life’s energy

Answer 4

Anabolic Processes are those that cause building of molecules

An example, in photosynthesis, is when chloroplasts take carbon dioxide and water to produce organic molecules (glucose) and oxygen

Catabolic processes are those that break down molecules

An example is cellular respiration which uses the mitochondria and is when organic molecules (glucose) and oxygen are used to produce CO2 and H2O and ATP (cellular energy)

These two processes form a cycle

ATP is produced from respiration and powers most cellular work, and at the same time heat is produce

Question 5

What do the processes of life go on to form in the end

Answer 5

Heat energy

Question 6

Describe the flow of energy at an animal scale (how are we supplied with and use/loose energy)

Answer 6

Organic molecules in food (e.g. glucose) are digested and absorbed, and in this process heat energy is released (gut is very active and uses a lot of energy to produce heat - squeezing food, and metabolism releases heast - ion pumps).

Furthermore, energy is lost in faeces - some waste
This produces nutrient molecules

These nutrient molecules can be processed/used to produce carbon skeletons - like amino acids, some of the skeletons of which we can use for energy. With this said, we need to release the nitrogen part of the amino acids (comes out in urine, or in gills in fish), which means energy is lost

The carbon skeletons can be used to build things (biosynthesis, to build muscle - heat lost), or stored as fat for leaner times (to become future nutrient molecules - heat lost)

Nutrient molecules or carbon skeletons (like those of amino acids) in body cells can also be used in cellular respiration, which also releases heat to produce ATP and more carbon skeletons
The ATP can be used for cellular work (heat released when using it) or biosynthesis (heat)

NOTE: The common theme is that everything produces heat

Question 7

Describe the difference in energy released from different foods

Answer 7

Different food sources release different amounts of energy when combusted/burnt (kJ/g)

From least to most:
- Carbohydrate (although we get the most amount of energy in animals due to how we manipulate and extract it)
- Protein (basically the same)
- Alcohol
- Fat

Question 8

How is our energy stored

Answer 8

Key note is that we store most of our energy as fat because it is light (doesn’t attract water), we can pack it around everywhere such as bum, stomach, and muscle (useful for exercise as can access)

We also store some energy as muscle and liver glycogen (why when people starve they break down muscle)

Fuel consumption of the average 70 kg male after an overnight fast:
- 0.4% of our energy stores are as muscle glycogen
- 0.2% of our energy stores are in liver glycogen
- 85% as fat

Question 9

Describe how fuels and energy is extacted from stores

Answer 9

Liver glycogen and (deanimated) amino acids can be broken down by the liver and enter the bloodstream, which can go to tissues

Muscle is full of ATP, PCr (phosphocreatine), fats (triglycerides), glycogen, and carbon skeletons from amino acids, but cannot export what it has to the rest of the body (it has to use what is has itself)

Adipose tissue - can release fatty acids from triglycerides, some of which can go back to the liver (to make something we will go into later)

The deaminated amino acids, glucose, and free fatty acids from these things can all go into the mitochondria to produce ATP

Question 10

Describe the stages of catabolism regarding the formation and use of Acetyl Coa

Answer 10

Acetyl-CoA is a hub molecule:

In a ‘stage 1’, fatty acids and glycerol from fat, glucose and other sugars from polysaccharides, and amino acids from proteins, are broken down into monomers

In ‘stage 2’ they are used to produce Acetyl CoA (an activated form of acetate), which can be fed into the citric acid cycle (which pumps out CO2 from our breath, and the electrons will be striped to be used in the electron transport chain in the mitochondria to produce a lot of ATP)

Question 11

Describe the basics of ATP - lifes (almost) universal currency

Answer 11

We use the vast majority of our energy via ATP

ATP is made from adenine (2 rings), ribose sugar, and three phosphate groups

The bonds within the phosphates are phosphoanhydride bonds

Question 12

Describe the ATP-ADP cycle

Answer 12

The energy of catabolism/metabolism (breaking down food) is used to take ADP and inorganic phosphate to produce ATP.

Notes that catabolism is exergonic/an energy-releasing process (the released energy is used to form ATP)

If we take the ATP and add water, we can hydrolyse the ATP and release energy to produce ADP and inorganic phosphate,

We can use this energy for cellular work, which are endergonic/processes that require energy (from the ATP)

Question 13

Describe some usages of ATP

Answer 13

Ion pumping/transporting solutes (e.g. by phosphorylating and changing the shape of a protein)

Move vesicles up and down a microtubule
An example is a motor protein moving down a microtubule dragging a vesicle (uses ATP), in muscle contraction,

Muscle contraction:
Myosin - which has evolved from something similar - uses ATP to release form the actin to allow for muscle contraction (when animals die, their muscle are stiff as the myosin doesn’t have energy to be released form actin, it has to be degraded)

To add things to solutes like sugars

Question 14

Describe some of the basics of ATP that make it so important

Answer 14

ATP is not really “universal” (it is for the sake of the exam though), cells use GTP, UTP and also creatine phosphate (CrP*) for energy
However, ATP is the most abundant, frequently used and likely ancestral.

Importantly, in the cell, most hydroxyl groups of phosphate are ionised (-0-), which is important because it is electrical/charged - where the energy comes from

The phosphoanhydride bond of ATP (bonds between the phosphates) are relatively stable in water at physiological pH (most stable of all nucleotides)

When broken, there is an overall release of energy on hydrolysis is an exothermic reaction (outwards flow of energy/releases heat).

Although other bonds can yield more energy, they are less water stable (hence may be broken instantly)

Question 15

Where did ATP come from (extra)

Answer 15

Importantly, it takes 6 ATP to make 1 ATP from scratch (making the sugar and nucleotide and phosphate)
So there needed to be something that can transfer inorganic phosphate to molecules

Bacteria has a pathway that utilised Acetyl phosphate (acetate with a phosphate) and an acetyl kinase spontaneously - which can be used to form ATP from ADP
But the enzyme is not needed, if you have Fe3+ (and ADP) with acetyl phosphate you can produce ATP

Adenosine is the only one that worked, and it worked in water

So in summary, ATP likely came from ADP and acetyl phosphate (a polyphosphate)

Question 16

Describe polyphosphates

Answer 16

Bacteria use polyphosphates (long chains of phosphates), which have energy in them, and they have enzymes that can use them as an energy source like ATP

Furthermore, when we get sepsis, we release polyphosphates as well, and due to the charges they wrap around metal ions such as iron - it is chelated - so it reacts with the iron (iron can be problematic as very reactive w/ membranes can cause haemolysis - when RBCs rupture and more iron gets into blood)

Question 17

Describe how ATP works

Answer 17

Phosphate is negatively charged, and there will be charge delocalisation/resonance

With two phosphates joined in the middle, the two negative chares on the two groups will repel, causing the negative charge to go on either side

With three phosphates (like in ATP), once again the negative charges will go to either sides.

When you add adenosine on one end, it gives directionality to the molecules and it pushes one way, which means that there is a force on the terminal phosphate so that it wants to leave. Furthermore, the adenosine can be bound to enzymes to expose the phosphates. Finally, ATP also chelates/associates with a metal - magnesium or calcium - which means that the force is magnified more as it brings the negative charges to the end

As such, the energy released from the terminal phosphate (Pi ) of anhydride bond hydrolysis, is high.

You can think of ATP as giving things an electrostatic charge through the phosphate: in a protein the ATP is transferred which activates the protein, which can then change the shape of the protein, and then the ATP is hydrolysed and dissociates, which means the charge state can change, and then it can go back to its previous state

The free energy of formation (∆fG0) - energy required for ATP to be formed - of ATP is greater than the sum of the “products of formation” of ADP + Pi

Therefore if we release the phosphate from the ATP, we get a lot of energy back, which can drive reactions that otherwise would go too slowly or not at all

Question 18

What is the equation for Gibbs free energy

Answer 18

ΔG = ΔH - TΔS

Question 19

Name the laws of thermodynamics and how they related to Gibbs free energy

Answer 19

1) Energy can not be created or destroyed, it changes form
2) The Universe is becoming increasingly disordered

1st law of thermodynamics:

ΔH = q (heat) + w (work)
The change in enthalpy = heat + work done

2nd law of thermodynamics:

• The universe tends towards disorder (ENTROPY IS DISORDER/EQUILIBRIUM)
• The symbol for entropy is S
• Non-equlibirum = ordered (low entropy)
• Equilibrium = less order (high entropy)
• When reaction reach equilibrium they go no further
• Life fights equilibrium/entropy (think of membrane potentials)

Question 20

What do we need for a reaction to occur

Answer 20

For a reaction to occur, we want the ΔG to be really negative, so we want the change in order to increase a lot

Question 21

Describe the use of Gibbs free energy

Answer 21

GIbbs free energy predicts whether a reaction occurs spontaneously (will flow/react once activated)

It predicts the maximum possible change in concentrations between reactants and products

The more negative (- ΔG) the more work can be done

But note it does not predict the rate at which reactions will occur - e.g. there may be limits like diffusion limits
Important for exam

Question 22

Gibbs Free energy examples

Answer 22

When someone jumps downwards, they decrease their gibbs free energy as they fall (as when high up the potential is high)

When molecules diffuse they increase entropy

When molecules are combusted and broken down (e.g. glucose), entropy increases and in doing so usually release heat

When we pump ions to one side of a membrane, we decrease entropy

Hydrolysis of ATP by myosin would release heat itself but also due to movement there will also be work. Furthermore there is an increase in entropy as ATP is broken down into ADP and inorganic phosphate (and a proton), rearrangement of the myofibrils and the liquid around them, and also movement of the molecules

Question 23

How do we use free energy gradients for energy

Answer 23

Using a free energy gradient we can generate energy - as it moves towards equilibrium - and use it to power metabolism
But it comes to equilibrium and is only for a short period - this is similar to how anabolic metabolism works, as if we don;t breath lactate builds up and eventually we need to stop
If there is constantly a free energy gradient somehow, it will keep going
This is close to how life works
Furthermore, there can be more turbines (like in mitochondria) and hence making it more efficient at harnessing energy (e.g. in the mitochondria)

Question 24

Describe polyphosphates

Answer 24

Bacteria use polyphosphates (long chains of phosphates), which have energy in them, and they have enzymes that can use them as an energy source like ATP

Furthermore, when we get sepsis, we release polyphosphates as well, and due to the charges they wrap around metal ions such as iron - it is chelated - so it reacts with the iron (iron can be problematic as very reactive w/ membranes can cause haemolysis - when RBCs rupture and more iron gets into blood)

Question 25

How does ΔG relate to ATP when the phosphates are removed

Answer 25

Breaking down ATP to AMP gives 32.2 kj/mol

Breaking down ATP to ADP gives 30.5kj/mol

Therefore nearly all of the energy is in the last phosphate

Furthermore, ATP is most likely to go from ATP to ADP than ADP to ATP (although is still theoretical reversible)

Question 26

Use the law of mass action to describe ATP vs ADP concentrations in the heart

Answer 26

In the heart there is about 8-10mM of ATP, while there is 0.05-0.15mM of ADP (about 200x more ATP, but in some tissues the ratio is 1000/1 ATP/ADP)

The reason why is that with more ATP you can generate more force due to higher difference and therefore more energy released

In the other way - where we have more reactants that have less energy and less energetic products - we need to use energy (endergonic), which we can use ATP for to drive the reaction

This is also related to product inhibition - if we have lots of product it can feed back and stop reaction as well

Question 27

Relate ΔG to Cellular respiration:

Answer 27

Cellular respiration is energetically favourable as has very negative ΔG

Therefore it is exergonic

Energy from glucose is conserved in ATP, but when doing work, will be released as heat

Question 28

Relate ΔG to Glutamate

Answer 28

Glutamate is a simple amino acid and neurotransmitter that acts as a signal in bacteria for food and it is what makes us hungry and feel good through glutamate receptors

It is an excitatory neurotransmitter that is sent across synapses

However, with too much glutamate it can be dangerous - you can get seizures

Fortunately, glutamic acid/glutamate and ammonia can be used to produce glutamine to clear the glutamate

However, based on the positive ΔG (of turning glutamic acid and ammonia into glutamine), this reaction will not happen by itself

However, using ATP we can phosphorylate glutamic acid/glutamate, which changes its state to make it more favourable for the ammonia to bind and produce glutamine

We also need the enzyme glutamine synthetase for this reaction

With all of this, the ΔG becomes negative and therefore can occur spontaneously