Endergonic Reactions and Enzyme Regulation part 4

Endergonic Reactions and Energy Coupling

Endergonic reactions require energy input.
Cells perform three main types of endergonic reactions:
- Chemical reactions (e.g., building macromolecules from monomers).
- Transport processes (e.g., pumping ions against concentration gradients).
- Mechanical work (e.g., muscle cell contraction).
Endergonic reactions are powered by coupling them with exergonic reactions.
- Energy released from an exergonic reaction drives the endergonic reaction.

ATP (adenosine triphosphate) hydrolysis is a common exergonic reaction used to power endergonic reactions.
The sodium-potassium ATPase pump uses ATP hydrolysis to transport ions.
- The enzyme hydrolyzes ATP into adenosine diphosphate (ADP) and inorganic phosphate (Pi), changing its conformation and pumping ions.
Motor proteins, like kinesin, use ATP hydrolysis to move along microtubules.
- ATP binding, hydrolysis, and release power the movement.

ATP consists of adenine (nitrogenous base), ribose (sugar), and a triphosphate group.
- The ribose sugar indicates it is a building block for RNA polymers.
- The presence of a hydroxyl group (-OH) at the 2' carbon of the ribose distinguishes it from deoxyribose.
The triphosphate group has three negatively charged phosphate groups in close proximity, causing repulsion and instability.
This region of the molecule is less stable due to the repulsion of like charges.
ATP can be thought of as a chemical equivalent of a compressed spring.

Hydrolysis involves adding water to ATP, cleaving off the last phosphate group.
- ATP + H2O \rightarrow ADP + Pi + Energy
This results in adenosine diphosphate (ADP) and inorganic phosphate (Pi).
ADP is more stable than ATP because there are only two negative charges in close proximity.
The hydrolysis of ATP releases energy because the molecule transitions from a less stable (higher free energy) to a more stable (lower free energy) state.

ATP is a renewable resource; ADP can be phosphorylated to regenerate ATP.
- ADP + P_i + Energy \rightarrow ATP
Phosphorylation of ADP is an endergonic reaction, requiring energy input.
The energy for ATP regeneration comes from catabolic reactions, such as cellular respiration (discussed in chapter 9).
Cells constantly hydrolyze ATP to drive endergonic reactions and then phosphorylate ADP to remake ATP.
This cycle happens at a very high rate.

If the energy released by hydrolyzing ATP to ADP and inorganic phosphate is insufficient, ATP can be hydrolyzed to adenosine monophosphate (AMP) and pyrophosphate (PPi).
This reaction releases more energy than the ATP to ADP conversion.
- ATP + H2O \rightarrow AMP + PPi + Energy
Pyrophosphate (PPI) still has instability due to the negative charges in close proximity.
Pyrophosphate can then be further hydrolyzed into two inorganic phosphate molecules.
- PPi + H2O \rightarrow 2P_i + Energy
This second hydrolysis releases additional energy.
The end products are adenosine monophosphate (AMP) and two independent phosphate groups.
Hydrolyzing ATP to AMP and PPi releases roughly twice as much energy.

GTP (Guanosine triphosphate) hydrolysis also releases energy, similar to ATP hydrolysis.
The energy release is due to the instability caused by the negative charges in close proximity in the triphosphate group, not the identity of the nitrogenous base.
Many enzymes and molecular machines have evolved to use ATP as their primary energy source.

Coupled reactions involve using the energy released from an exergonic reaction (e.g., ATP hydrolysis) to drive an endergonic reaction.
Specific enzymes facilitate these coupled reactions.
Enzymes couple ATP hydrolysis directly to a chemical reaction.
Example: conversion of glutamate to glutamine.
- Glutamate + Ammonia → Glutamine requires energy (+3.4 kcal/mol).
The enzyme glutamine synthetase catalyzes this reaction.
Glutamine synthetase couples ATP hydrolysis to the conversion of glutamate to glutamine.
- ATP → ADP + Pi releases energy (-7.3 kcal/mol).
The enzyme phosphorylates glutamate, creating a phosphorylated intermediate.
Glutamate + ATP \rightarrow Phosphorylated\, Intermediate + ADP
The phosphorylated intermediate is more reactive.
Ammonia displaces the phosphate group, forming glutamine.
Phosphorylated\, Intermediate + Ammonia \rightarrow Glutamine + P_i
The overall coupled reaction is exergonic:
- Glutamate + Ammonia + ATP \rightarrow Glutamine + ADP + P_i ∆G = -3.9 kcal/mol
The energy from ATP hydrolysis is used to phosphorylate glutamate, making it more likely to combine with ammonia to form glutamine.
Coupled reactions are exergonic overall, even though one step requires energy.

Enzymes are powerful catalysts that can quickly convert substrates into products.
Regulation of enzyme activity is important to prevent unnecessary reactions.

Competitive inhibitors compete with the natural substrate for binding to the active site.
The inhibitor binds to the active site, blocking the substrate from binding.
The competitive inhibitor has some structural similarity to the substrate.
Binding is not permanent; there is binding and unbinding.

Noncompetitive inhibitors bind to a site away from the active site.
Binding of the inhibitor changes the shape of the enzyme, preventing the substrate from binding to the active site.
Conformational change is important to function.
Noncompetitive inhibition is also usually temporary and reversible.

Irreversible binding of an inhibitor to an enzyme permanently inactivates the enzyme.
Toxins and poisons can bind irreversibly to enzymes, leading to their inactivation.
This is very harmful to the organism. Most often, when we're using it to regulate, it is reversible binding, whether it bound there or whether it bound to a place outside the active site.