Lecture 20 - Bioenergetics

What makes ATP the "energy currency" of the cell?

ATP is considered the "energy currency" of the cell because:

1. Its hydrolysis yields a large amount of free energy.

2. It has an intermediate phosphoryl group transfer potential (PGTP).

3. It is kinetically stable and does not hydrolyze spontaneously.

4. It is versatile — it can transfer its terminal phosphate to many types of molecules

What is the standard free energy change (ΔGº′) for ATP hydrolysis to ADP + Pi?

ΔGº′ = –30.5 kJ/mol
This reaction is highly exergonic and is commonly used to power endergonic processes.

Why does ATP hydrolysis release energy?

1. Relief of charge repulsion (ATP has 4 negative charges).

2. Products (ADP + Pi) have more resonance forms, increasing entropy.

3. ADP dissociates an additional proton spontaneously.

4. Products are better solvated by water, stabilizing them.

What is phosphoryl group transfer potential (PGTP)?

PGTP is the ability of a phosphorylated compound to donate its phosphate group to another molecule.
It is numerically equal (but opposite in sign) to the ΔGº′ of hydrolysis.
ATP’s PGTP = +30.5 kJ/mol (ΔGº′ = –30.5 kJ/mol).

Why is having an intermediate PGTP important for ATP?

Because it allows ATP to act as both a phosphate donor (in reactions where energy is needed) and, when converted to ADP, a phosphate acceptor (in energy-yielding reactions).
This makes ATP extremely versatile in metabolism.

What is substrate-level phosphorylation?

It is ATP generation by direct transfer of a phosphate group from a high-PGTP compound (e.g., PEP or 1,3-BPG) to ADP.
Example:
PEP + ADP → Pyruvate + ATP
ΔGº′ = –31.5 kJ/mol (overall exergonic)

Why is ATP kinetically stable despite its hydrolysis being exergonic?

The reaction has a large activation energy and requires specific enzymes (e.g., ATPases, kinases) to occur.
Thus, ATP doesn’t hydrolyze randomly, preserving cellular energy.

What are kinases and phosphatases?

• Kinases transfer the terminal phosphate of ATP to another molecule.

• Phosphatases remove phosphate groups from molecules.

What roles does phosphorylation play in cells?

a) Increases free energy of the target molecule
b) Adds negative charge, affecting membrane retention
c) Induces conformational change, allowing:

• Enzyme activation/inhibition

• Ion transport

• Signal transduction

How does phosphorylation regulate pyruvate dehydrogenase (PDH)?

Phosphorylation by a kinase converts PDH to its inactive form.
Dephosphorylation can reactivate it.

How does ATP relate to glutamine synthesis?

ATP hydrolysis drives the endergonic reaction:
Glu + NH₃ → Glutamine
By coupling to:
ATP → ADP + Pi
Overall:
Glu + NH₃ + ATP → Glutamine + ADP + Pi
ΔGº′ = –16.3 kJ/mol (overall exergonic)

Why is ATP considered a carrier of energy?

Because it temporarily transfers energy from fuel molecules (like glucose and fats) to processes that need it, such as biosynthesis and movement.

Why is ATP not considered a store of energy?

Because the body holds very little ATP at any time (~0.5 lbs), and it is constantly regenerated (~100 lbs/day). Long-term energy is stored in more stable molecules like glycogen and fat.

What are the three biological pathways to generate ATP?

• Substrate-level phosphorylation (e.g., glycolysis)

• Oxidative phosphorylation (mitochondria)

• Photophosphorylation (chloroplasts in plants)

Why are ATP molecules used for most cellular energy needs instead of electron carriers like NADH or NADPH?

Because ATP can provide small, manageable amounts of energy suitable for many diverse cellular processes.
In contrast, NADH and NADPH transfer large amounts of energy and are better suited for bulk electron transfer, not fine-tuned regulation.
ATP is more versatile and better suited as a near-universal energy carrier.

How does ATP function as a link between catabolism and anabolism?

ATP acts as a common intermediate, capturing energy from catabolic processes (e.g., fatty acid breakdown) and supplying it to anabolic reactions and cellular work.
Its concentration remains relatively constant, as ATP formation and breakdown are balanced in a steady state.

Why is ATP hydrolysis useful for driving cellular reactions?

ATP hydrolysis is highly exergonic, meaning it releases a significant amount of free energy.
This energy can be used to power endergonic reactions by coupling them together.
ATP can be hydrolyzed to ADP + Pi or to AMP + PPi, both of which release enough energy to help drive otherwise unfavorable processes.

Why might cells hydrolyze ATP to AMP + PPi instead of just ADP + Pi?

Hydrolyzing ATP to AMP + PPi, and then further breaking down PPi, releases more energy than standard ATP hydrolysis.
This extra energy is helpful for reactions that are especially energy-demanding, such as some biosynthetic processes.

What is one major reason ATP hydrolysis releases energy?

Relief of charge repulsion — ATP has four negative charges that repel each other. Breaking it into ADP and Pi reduces this repulsion, making the products more stable.

How does resonance stabilization contribute to the energy released from ATP hydrolysis?

ADP and inorganic phosphate (Pi) have more resonance forms than ATP, which means they are more delocalized and stable, increasing the entropy of the system.

How does proton dissociation contribute to ATP hydrolysis energy release?

After hydrolysis, ADP loses an additional proton spontaneously, which further lowers the free energy of the products, making the overall reaction more exergonic.

What role does solvation play in ATP hydrolysis?

The hydrolysis products, ADP and Pi, are better solvated by water than ATP. This solvation stabilizes the products and contributes to the overall negative free energy change.

Is energy released from ATP hydrolysis due to breaking a “high-energy bond”?

No. Breaking a bond requires energy. The term “high-energy bond” is misleading.
The energy comes from the greater stability of the products — not from the bond itself.

Why is it important that ATP has an intermediate phosphoryl group transfer potential (PGTP)?

An intermediate PGTP allows ATP to act as both a donor of phosphate (as ATP) and an acceptor (as ADP).

• If PGTP were too high, ATP would be hard to regenerate and might release more energy than needed — wasting energy.

• If PGTP were too low, ATP wouldn't release enough energy to drive cellular work.
  Thus, its intermediate PGTP makes it efficient and versatile.

How can compounds with higher PGTP be used to generate ATP?

Molecules like phosphoenolpyruvate (PEP) have a higher PGTP than ATP, meaning they can donate their phosphate to ADP to form ATP.
This occurs in reactions where the overall ΔG is still negative — a process called substrate-level phosphorylation.

How does ATP activate lower-energy compounds in metabolism?

Some molecules, like glucose, have low PGTP and can't be phosphorylated on their own.
ATP donates a phosphate to them, increasing their energy and making them more reactive, as seen in the formation of glucose-6-phosphate.

What does it mean that ATP is kinetically stable?

ATP does not spontaneously hydrolyze often because the reaction has a large activation energy barrier.

Why is the large activation energy for ATP hydrolysis important?

It prevents non-enzymatic hydrolysis, which would waste ATP’s potential energy.

How do enzymes ensure ATP energy is used efficiently?

Enzymes that utilize ATP are highly specific and regulated, releasing energy only at the right place and time.

What makes ATP a versatile molecule in cells?

ATP can transfer its terminal phosphate group (phosphorylation) to many types of molecules including proteins, lipids, and sugars.

How does phosphorylation increase a molecule’s free energy?

It activates molecules by making subsequent reactions thermodynamically favorable, often by coupling with ATP hydrolysis.

Give an example of phosphorylation activating a molecule for a thermodynamically unfavorable reaction.

Glutamate is phosphorylated to glutamate phosphate (using ATP), enabling it to be converted to glutamine, a normally unfavorable reaction.

How does phosphorylation add charge to molecules and why is this important?

The added phosphate group is charged, which prevents the molecule from diffusing out of the cell through the lipid membrane.

What is an example where phosphorylation traps a metabolite inside a cell?

The first step of glycolysis, where glucose is phosphorylated to glucose-6-phosphate, increasing free energy and trapping it inside the cell.

How does phosphorylation affect protein conformation?

Adding a phosphate group can change the protein’s shape by altering interactions, often acting like a switch to turn enzymes or pathways on or off.

How does phosphorylation regulate enzyme activity?

It can cause conformational changes that either block (turn off) or open (turn on) an enzyme’s active site, e.g., pyruvate dehydrogenase is inactivated by phosphorylation.

How can phosphorylation be used to pump ions against their concentration gradient?

ATP hydrolysis coupled with phosphorylation provides energy to power ion pumps, moving ions against their gradient.

How does phosphorylation regulate cell signaling pathways?

For example, receptor tyrosine kinases phosphorylate each other upon ligand binding, activating downstream phosphorylation cascades. Malfunction here can contribute to cancer.

Is ATP a storage form of chemical energy or a carrier?

ATP is a carrier of chemical energy, not a storage form.

How much ATP does the average human body contain?

About 0.5 pounds.

How much ATP does the average human use daily?

About 100 pounds.

How often is each ATP molecule regenerated in the body?

Approximately every 7 minutes.

Why is ATP considered a carrier rather than a storage molecule of energy?

Because it is constantly regenerated from ADP and Pi, transferring energy from storage molecules like carbohydrates and fats to where it’s needed.

What happens during substrate-level phosphorylation?

A phosphoryl group is transferred from a molecule with high phosphoryl group transfer potential (PGTP) directly to ADP, forming ATP.

Give an example of substrate-level phosphorylation.

The transfer of a phosphate from phosphoenolpyruvate (PEP) to ADP to form ATP and pyruvate.

Where does oxidative phosphorylation occur?

In mitochondria.

What drives oxidative phosphorylation?

Energy-releasing redox reactions that are coupled to ATP formation.

What is photophosphorylation?

The formation of ATP in chloroplasts using energy from visible light absorbed during photosynthesis.

Which organisms perform photophosphorylation?

Plants and some microorganisms.

: What is a thioester bond?

A bond formed between a carbonyl carbon and a sulfur atom (–C(=O)–S–), such as in acetyl-CoA.

Why do thioester bonds store more free energy (G) than oxygen esters?

Because thioester bonds are not resonance stabilized, making their hydrolysis more exergonic.

Why is acetyl-CoA considered a high-energy intermediate?

Its thioester bond can be hydrolyzed to release a large amount of free energy, which can be used to drive biosynthetic reactions.

versatility of ATP example response

“ ATP is a versatile energy carrier because it can donate its terminal phosphate group to a wide range of molecules in phosphorylation reactions. This transfer increases the free energy of molecules, making unfavorable reactions proceed, as seen in the synthesis of glutamine from glutamate. Phosphorylation also adds negative charge, which can trap metabolites like glucose-6-phosphate inside cells. Additionally, adding a phosphate group to proteins can cause conformational changes that regulate enzyme activity, turning them on or off. ATP is also used in active transport (e.g., ion pumps) and cell signaling pathways (e.g., activation of receptor tyrosine kinases). These diverse roles make ATP central to cellular metabolism, regulation, and communication. “ (written with AI)