Lecture 21: ATP and High-Energy Compounds; Electron Carriers

What is the principal donor of free energy in biological systems?

ATP

What is ATP used to do?

• fuel enzymatic reactions

• transport of molecules

• do mechanical work

ATP molecules are consumed with how many seconds of their generation?

within 60 seconds

How is ATP regenerated?

via oxidation of carbon in fuel molecules like glucose, fats, and proteins

How much ATP does the resting human consume in a day?

40 kg/88 lbs of ATP

How much ATP does the typical human adult body contain?

about 100 g of ATP

How many times is each ATP molecule recycled a time day?

400 times/day

Why is ATP called the cellular energy currency?

• ATP has a phosphoryl-transfer potential that is intermediate among the biologically important phosphorylated molecules

• high-phosphoryl-transfer-potential compounds derived from the metabolism of fuel molecules are used to power ATP synthesis

• ATP donates a phosphoryl group to other biomolecules to drive unfavorable reactions and facilitates their metabolism

What is the delta G^o’ of hydrolysis of the phosphoanhydride bond between the gamma and beta phosphorus?

-7.3 kcal/mol or -30 kJ/mol

Which products result from a phosphoanhydride bond cleavage between the gamma and beta phosphorus?

ADP and Pi

What is the delta G^o’ of hydrolysis of the phosphoanhydride bond between the beta and alpha phosphorus?

-10.9 kcal/mol or -46 kJ/mol

Why does ATP/ADP always form complexes with Mg²⁺?

Mg²⁺ coordination makes phosphorus more electrophilic (tendency to attract or acquire electrons)

What is the basis for the high phosphoryl group-transfer potential of ATP?

• electrostatic repulsion

  • at pH 7, ATP carries 4 -ve charges

  • ADP has 3 -ve

  • repulsion is reduced upon hydrolysis

• resonance stabilization

  • orthophosphate (P_i0 has 4 resonance forms

• stabilization due to hydration

  • water can bind more effectively to ADP and P_i than it can to the phosphoanhydride portion of ATP

True or False: Nucleophilic attack by water or -OH group can occur at any of the three phosphates of ATP.

true

What is a phosphoryl transfer?

the transfer of ADP; common reaction

What is a pyrophosphoryl transfer?

the transfer of AMP; rare reaction

What is an adenylyl transfer?

the transfer of PP_i; common reaction

Why is ATP kinetically stable?

ATP hydrolysis has a high energy of activation

How does ATP hydrolysis exceed the activation barrier?

the ATPase enzyme grabs an ATP molecule and helps it over the hump—channeling that energy from the ATP hydrolysis to a chemical reaction that needs it

Why don’t we store all our energy as ATP?

• ATP is hydrolyzed easily and has a short half-life

• many reactions are allosterically regulated by ATP levels, especially those that generate energy

How do muscle cells store high-energy phosphate bonds?

in the form of Creatine phosphate

True or False: Creatine phosphate (PCr) acts as a quick energy source in muscles.

true

is the hydrolysis of creatine phosphate favorable or unfavorable?

favorable; the reaction has a negative delta G^o’

Why does PEP have a large free energy change on hydrolysis?

• P_i is stabilized through resonance

• keto form of pyruvate is more stable and is favored

Why does 1,3-diphosphoglycerate (DPG) have a large free change on hydrolysis?

• 3-phosphoglyceric (hydrolysis product) has more resonance structures

• 3-phosphoglycerate can be stabilized through resonance

• increased amount of H⁺—leading to more entropy

Why is acetyl CoA a high-energy metabolite?

it contains a thioester bond

What does CoA carry?

acyl groups

Acyl groups are linked to R-SH to form thioesters in which processes?

• TCA cycle

• fatty acid catabolism

• fatty acid synthesis

Why are thioester bonds higher in energy than ordinary esters?

• the large atomic size of sulfur reduces the electron overlap between C and S, so that the partial C=S structure does not contribute significantly to resonance stabilization

• thioesters are more unstable relative to esters

True or False: The flow of e- in oxidation-reduction reactions is responsible for all work done in living organisms.

true

What does it mean when a chemical species gets oxidized and reduced?

loss of electrons and gain of electrons, respectively

True or False: Oxidation and reduction reactions are always coupled.

true

True or False: Electrons can flow spontaneously between two chemical species, driven by an electro-motive force (EMF) proportional to the difference in electron affinity.

true

What are the two main types of cellular fuels?

glucose and fatty acids

True or False: Only 10-15% of energy is derived from protein catabolism.

true

How are electrons transferred from donor to acceptors?

• director electron transfer

  • Fe²⁺/Fe³⁺ to Cu⁺/Cu²⁺

• H⁺ atoms

• electrons transferred as H^- ions

  • occurs in the case of NAD-linked dehydrogenases

• direct combination with oxygen

  • oxidation of hydrocarbon to alcohol

True or False: Electrochemical potentials are additive for coupled reactions.

true

True or False: Under standard conditions, a positive delta E^o’ but a negative delta G^o’ signifies an exergonic reaction.

true

True or False: NAD(P)H carries redox equivalents as a hydride; NAD⁺/NADH in catabolism and NADP⁺/NADPH in anabolsim.

true

What wavelength does NAD⁺ and NADH absorb light at?

260 nm and 340 nm, respectively

True or False: NAD⁺/NADH are generally involved in oxidation of alcohols and aldehydes in which 2 electrons are removed and added to NAD⁺ forming NADH.

true

True or False: NAD⁺/NADH and NADP⁺/NADPH are soluble and loosely bound to the enzyme and act as co-substrates.

true

Where is FAD/FMN usually embedded?

the active site of the enzyme

What is important to know about FAD/FMN?

• reduced by 1 electron at a time

• tightly/covalently bound to an enzyme

• needs an external e- donor/acceptor

• generally involved in oxidations in which electrons are removed from separate atoms (formation of double bonds)

What is most of the ATP in the cell made through?

oxidative phosphorylation

What is involved with oxidative phosphorylation?

1. the transfer of electrons from substrates to NAD⁺ [NADH] and FAD [FAD(2H]

2. to the mitochondrial electro transport chain

3. the transfer of electrons to oxyen

If oxygen is not available, what happens to oxidative phosphorylation?

electrons cannot be transferred to oxygen, and most of the ATP production will cease

How many ATPs does anaerobic glycolysis produce?

2 ATP