Lecture 3: Thermodynamics of Phosphate compounds

Question 1

What is the long name for Pi?

Answer 1

Orthophosphate (PO4^3-)

Question 2

What is the long name for PPi?

Answer 2

Pyrophosphate (P2O7^4-)

Question 3

Give an examples of another type of high energy compound.

Answer 3

acyl phosphates

Question 4

What is a high energy bond?

Answer 4

A bond that is more negative than -25 kJmol-1

Question 5

What are the phosphoanhydride bonds in ATP high energy?

Answer 5

1) Resonance stabilisation less in phosphoanhydride bond than in hydrolysis product
2) Greater electrostatic repulsion in phosphoanhydride compared to hydrolysis product
3) Smaller solvation energy of a phosphoanhydride bond compared to hydrolysis product.

Mostly it is thought that reasons 1 and 2 are most important, but some scientists argue that reason 3 is most important.

Question 6

Give 4 examples of free energy sources/shuttles.

Answer 6

• phosphate anhydrides
• enoyl phosphates
• some thioesters
• compounds containing N-P bonds

Question 7

What does PEP stand for?

Answer 7

Phosphoenolpyruvate

Question 8

What is the Gibbs free energy of PEP –> Pyruvate + Pi?

Answer 8

-62 kJmol-1 (favourable)

Question 9

What is the Gibbs free energy of ATP synthesis?

Answer 9

+31 kJmol-1 (unfavourable)

Question 10

Is PEP or ATP a high energy compound? Explain using coupled reactions involving the two.

Answer 10

Phosphoenolpyruvate is a higher energy compound than ATP, so transfer of the phosphate from PEP can synthesise ATP.
The coupled reaction is
PEP + ADP –> pyruvate + ATP delta G = -31 kJmol-1 (favourable)

Question 11

What is the phosphoryl transfer potential measured against (as a reference)?

Answer 11

The hydrolysis reaction with water (phosphoryl transfer to water), which is always a thermodynamically favourable process (delta G = negative), no matter which molecule provides the phosphate group.

Question 12

Relate the phosphoryl transfer potential to the delta G of the reference hydrolysis reaction for that molecule.

Answer 12

The greater the phosphoryl transfer potential of a compound with a phosphate group, the more energetically favourable is its hydrolysis reaction (more negative delta G).

Question 13

Where on the scale is the phosphoryl transfer potential of ATP and how is this important?

Answer 13

Intermediate, in the middle of the scale. This is important because this means that ATP can donate phosphate to lower energy compounds and can accept phosphate from higher energy compounds. The highly exergonic phosphoryl transfer reactions of nutrient degradation are coupled to formation of ATP.

Question 14

Give the scale of phosphoryl transfer potentials.

Answer 14

• 62 PEP
• 49 1,3-bisphosphoglycerate
• 43 Creatine phosphate
• 30 ATP
• 33 PPi
• 4 AMP
• 10 Glycerol-1-phosphate

Question 15

Is the hydrolysis of acetyl CoA favourable or unfavourable?

Answer 15

Favourable. Delta G = -32 kJmol-1

Question 16

Give the ways the ATP is consumed.

Answer 16

• early stages of sugar breakdown producing low energy phosphate compounds (glycolysis, glucose + ATP –> Glucose-6-phosphate)
• interconversion of nucleoside triphosphate:
  ATP + NDP ADP + NTP (where N is a nucleoside) catalysed by nucleoside diphosphate kinase (no base specificity - can be A, G, T, C, U)
• physiological processes such as muscle contraction and active transport against concentration gradient
• additional phosphoanhydride cleavage:
  ATP —> AMP + PPi, then PPi –> 2 Pi. This provides extra energy for fatty acid acetyl CoA synthesis and nucleic acid synthesis

Question 17

What is the adenylate kinase (myokinase) reaction?

Answer 17

Normally ATP ADP + Pi, but there is a notable exception called the adenylate kinase reaction. In this reaction 2 ADP ATP + AMP.
This means that when muscles are contracting rapidly and using lots of ATP and producing lots of ADP, the adenylate kinase reaction goes to the right, using up ADP and replenishing half the ATP. The reaction also produces AMP, dramatically increasing the concentration of AMP in the cell. AMP is an activator of energy producing pathways, by allosteric activation and by activating cAMP-dependent protein kinase, which regulates many metabolic pathways. AMP acts as signal telling the cell that energy levels are very low and prompts nutrient oxidation to replenish ATP supplies.
When ATP is replaced, myokinase reaction moves to the left, AMP concentration falls and the signal is turned off.

Question 18

Comment on the rate of ATP turnover.

Answer 18

It is very rapid. ATP is a free energy transmitter not a reservoir. The ATP pool can supply energy for about 1 minute.

Question 19

What is the function of phosphocreatine?

Answer 19

Phosphocreatine provides a high energy reservoir for ATP formation.
ATP + creatine —> Phosphocreatine + ADP (Delta G = +12.6 kJmol-1)
We store phosphocreatine and hydrolyse it to produce ATP when ATP levels are low.