Lecture 1 Phosphoryl group transfers and ATP Flashcards
Important properties of inorganic phosphate
- Phosphorus can form 5 covalent bonds.
- In Pi, four equivalent P - O bonds share some double-bond character.
- The double bond can be delocalized
- The central P atom has a partial positive charge and is electrophilic.
Phosphoryl group transfer of ATP
ATP is a phosphoryl group donor.
How does ATP transfer a phosphoryl group?
Enzymes
Enzymes that catalyze phosphoryl group transfer from ATP are called kinases. An example is hexokinase.
Structure of ATP
Adenosine triphosphate
- Adenine linked to ribose sugar via N-glycosidic bond to form Adenosine.
- Ribose linked to Pi via phosphoester and ester bond
- Pi linked via phosphoanhydride bonds to form AMP, ADP and ATP
What does high energy release during hydrolysis of ATP results in?
- Products with less electrostatic repulsion.
- Products with more resonance stabilization.
- Ionized, more stable products.
- Increase in entropy as several products generated per reactant (e.g., per ATP molecule).
- Greater degree of solvation of the products. (i.e. water and Pi interactions)
What are the energetics of ATP hydrolysis?
- ATP breaks down only slowly on its own as activation energy for hydrolysis is very high (~200 kJ/mol).
- Free energy of enzymatic hydrolysis (∆G) for 𝞬-phosphate is large (-31 kJ/mol).
- Guide ATP to its activation energy faster
- high energy bonds
High-energy bonds
Large negative ∆G of hydrolysis (-30 kJ/mol) → large amount of energy is released by hydrolysis of ‘high energy’ bonds.
What is the actual free energy of ATP hydrolysis called?
under intracellular conditions is often called its phosphorylation potential, ∆Gp.
Why does ∆G’ (standard conditions in biochemistry) ≠∆G’ᴼ(standard conditions in chemical reactions)?
- Not all organisms live at 25oC.
- The intracellular pH varies from ~6.5 to 8.0.
- Divalent cations such as Mg++ affect charge repulsion.
- The concentrations of reactants and products are not 1.0 M.
∆G’p for ATP hydrolysis
How can ∆G’p change?
adjust concentrations of the reactants and products
- more ADP hydrolysis unfavourable
- more ATP hydrolysis favourable
structure of acetyl-coenzyme A
- Has a thioester linkage
energetics of thioester linkage
‘high-energy’ bond
Hydrolysis of Acetyl Co-A
- Upon hydrolysis, the carboxylic acid can ionize and is resonance stabilized.
- Coenzyme A (CoA) is used in reactions involving the transfer of acyl/acetyl groups.
What are cofactors?
- A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme’s role as a catalyst
- convert inactive apoenzymes into active holoenzymes
- Cofactors can be considered “helper molecules” that assist in biochemical transformations.
- bind with electrons so they are taken from an electron-rich molecule and transferred to an electron-poor molecule
Structure of NAD+
- Has adenosine
- D-ribose
- nicotinamide
What part of NAD+ is can accept the electrons for transfer?
The nicotinamide
- the oxidized form is reduced when receiving the 2 e- from 2H
What is NAD+ derived from?
Niacin
- Nicotinamide is derived from niacin (vitamin B3).
- The biosynthetic precursor of these compounds is tryptophan.
- Nicotinic acid can be produced in the lab by the oxidation of nicotine.
- In the 1940’s, the name nicotinic acid was changed to niacin under pressure from anti- tobacco groups.
Structure of FAD
- adenosine
- Pi
- ribitol
- isoalloxazine ring
Where does FAD pick up electrons on its structure?
The isoalloxazine ring
- The iso alloxazine ring undergoes reversible 2-electron reduction to form FADH2 or FMNH2.
- Single electron reduction to form a semiquinone radical is also possible.
catabolism and anabolism with acetyl CoA
energetics of catabolism vs. anabolism
Catabolism generates ‘energy’ while anabolism consumes ‘energy’
