Ch. 8 Flashcards
What are the 2 different kinds of energy that drive all cellular reactions?
- Electrochemical energy (ion gradients)
- Chemical energy (high-energy molecules)
List the high-energy molecules cells use.
- ATP and nucleotide derivatives
- Phosphoenolpyruvate (PEP)
- Actyl-CoA and derivatives
- Acyl-phosphates
High-energy molecules have bonds that have a _____.
high free energy of hydrolysis
What does the squiggle (~) denote?
A high negative free energy of hydrolysis
Explain what having a “high group transfer potential” means.
Chemical group attached to the “squiggle” is transferred with a large free energy release to acceptor molecules
Explain what happens in a generic phosphoryl group transfer.
- Positively charged phosphorus is attacked by a nucleophile
- Chemical group Y is displaced with its bonding electrons, and the phosphoryl group is transferred to the hydroxyl, forming ROP
Why does the phosphorus atom in all phosphate groups carry a positive charge?
Because phosphorus forms double bonds poorly –> electrons in the bond are shifted toward the electron-attracting oxygen
What is a nucleophile?
An attacking atom with a pair of electrons seeking a positive center
Group transfer reactions are what type of reaction?
Nucleophilic displacements
What is the group transfer potential defined as?
The negative of the standard free energy of hydrolysis at pH 7
- Tendency of a molecule to donate the chemical group to a nucleophile
- Not really a potential in an electrical sense, but a free energy change per mole of substrate hydrolyzed
What are group transfer potentials used to estimate?
The direction in which a reaction will proceed
What types of modifications to metabolites can ATP make?
- Phosphorylation
- Pyrophosphorylation
- Adenylation
Transfers chemically activate metabolites for _____.
future steps
Why is ATP the central energy currency in the cell?
Because phosphate transfer releases a lot of energy
Why is so much energy released during ATP hydrolysis? (Hint: look at its structure)
- At pH 7 the phosphate groups are ionized
- This produces electrostatic repulsion between the negatively charged phosphates
Why are reactions during which phosphate is removed from ATP favored?
Because the electrostatic repulsion is decreased as a result of the hydrolysis
Any group that is _____ can attack the _____ phosphorus shown and result in phosphoryl group transfer. Give an example.
- electronegative
- electropositive
- Ex. Hydroxyl groups in sugars
Enzymes that catalyze phosphoryl group transfer reactions are called _____.
kinases
What is the difference between bond energy vs. free energy of hydrolysis?
- Bond energy = energy required to break a bond
- Free energy of hydrolysis = energy released when a bond is broken
What is the more energetic phosphoryl donor: ATP or PEP?
PEP
Why does PEP have a high phosphoryl group transfer potential?
Hydrolysis removes the phosphate allowing the enol form of pyruvic acid to tautomerize into the keto form
- Energy is released because the keto form is more stable than the enol form
The formation of a molecule with _____ bond energy will result in the release of energy.
higher
Why do acyl derivatives have high group transfer potentials?
Because they do not resonate well
- In a normal ester, 2 electrons shift from the oxygen to form a double bond during resonance –> oxygen acquires a positive charge
Why is resonance hindered in phosphate esters and thioesters?
- Because the positive charge on the phosphorus atom prevents electrons from shifting in from the oxygen to form a double bond –> would leave 2 adjacent positive centers
-
Thioesters don’t resonate as well
as normal esters because sulfur doesn’t form double bonds with carbon
Why is the hydrolysis of acyl derivatives energetically favored?
Because it leads to products stabilized by resonance with respect to the reactants
Match the enzymes to the reaction they catalyze. Why are these important?
Reaction (groups donated):
1. Acyl groups
2. CoA groups
3. Phosphoryl groups
Enzymes:
a. Kinases
b. CoA transferases
c. Transacylases
- Acyl groups = transacylases
- CoA groups = CoA transferases
- Phosphoryl groups = kinases
Importance: very versatile
- Fatty acids and proteins are synthesized via acyl group transfer reactions
- CoA transfer takes place during fermentative reactions in bacteria
- Acyl phosphates donate their phosphoryl groups to ADP to form ATP
Why are group transfer reactions central to all metabolism?
Because biological molecules are synthesized as a result of group transfer reactions
How does ATP donating other parts of the molecule contribute to biosynthesis?
- When these groups are transferred to an acceptor molecule, the acceptor molecule itself becomes a high-energy donor for subsequent biosynthetic reactions
- Energy from ATP can be transferred to other molecules, which can then drive biosynthetic reactions
- What happens if the α phosphate is attacked?
- What happens if the γ phosphate is attacked?
- AMP is the group transferred and PPi is the leaving group
- The phosphoryl group is transferred forming the phosphorylated derivatives and ADP as the leaving group
What determines the specificity of the attack?
The reaction depends upon which enzyme catalyzes the reaction
What are some bonds that ATP can form?
- Amide linkages
- Thioesters
- Esters
How is ATP made (2 pathways)? Where does each pathway occur?
- Oxidative phosphorylation (ATP synthase)
- Occurs in membrane - Substrate-level phosphoylation (SLP)
- Occurs in cytosol
Define substrate level phosphorylation (SLP).
Phosphorylation of ADP in the soluble part of the cell by means of a high-energy phosphoryl donor
SLPs are catalyzed by enzymes called _____.
kinases
What is the general reaction for SLP?
Diagram what happens during SLP.
- An oxygen in the β phosphate of ADP acts as a nucleophile and bonds to the phosphate phosphorus in the high-energy donor
- The phosphoryl group is transferred to ADP –> makes ATP
Phosphoryl donors for ATP synthesis during SLPs include _____.
- 1,3-bispohosphoglycerate (BPGA)
- Phosphoenolpyruvate (PEP)
- Succinyl-phosphate
- Acetyl-phosphate
What are the 4 major SLPs? What metabolic pathways do they occur in?
- 1,3-BPGA + ADP –> 3-PGA + ATP
- Glycolysis - PEP + ATP –> pyruvic acid + ATP
- Glycolysis - acetyl-P + ADP –> acetic acid + ATP
- Acetyl-P formed form acetyl-CoA formed from pyruvate - succinyl-CoA + Pi + ADP –> succinic acid + ATP + CoASH
- Citric acid cycle
How is 1,3-bisphosphoglycerate (BPGA) formed?
Phosphoglyceraldehyde dehydrogenase oxidizes phosphoglyceraldehyde (PGALD) into 1,3-BPGA
How does 1,3-BPGA make ATP?
- Donates a phosphoryl group to ADP in SLP
- Forms ATP and 3-phosphoglycerate
- Catalyzed by phosphoglycerate kinase
How is acetyl-CoA formed from pyruvate?
Usually made by the oxidative decarboxylation of pyruvate
What are the 3 enzyme systems in bacteria that decarboxylate pyruvate –> acetyl-CoA? Which are in aerobic vs. anaerobic bacteria?
- Pyruvate dehydrogenase
- Aerobic - Pyruvate-ferrodoxin oxidoreductase
- Anaerobic - Pyruvate-formate lyase
- Anaerobic
Pyruvate dehydrogenase is not usually found in fermenting bacteria. Why might this be?
- Pyruvate dehydrogenase reaction produced NADH
- Would be disadvantageous to fermenting bacteria because there is often no external electron acceptor that can reoxidize NADH into NAD+
What is acetyl phosphate made from?
Made from pyruvate via acetyl-CoA
Explain what happens in the pyruvate dehydrogenase reaction.
- 2 electrons that bond the carboxyl group to the molecules are transferred to NAD+
- CoA attached to the carbonyl group to form the acylated CoA derivative
How is succinyl-CoA made?
Made by oxidative carboxylation of α-ketoglutarate
- Occurs in the citric acid cycle
How is phosphoenolpyruvate (PEP) made?
Formed by a dehydration reaction catalyzed by enolase
What is PEP used for?
Used to regenerate ATP which is used to phosphorylate sugars in glycoslysis
