Cell Structure and Function Enzymes

Metastable State

A condition where a reaction is thermodynamically feasible but does not proceed at an appreciable rate

Isothermal

Constant in temperature (homeostasis), which describes the environment inside cells.

Activation Energy (Ea)

The energy barrier that determines the minimum kinetic energy molecules need to take part in a reaction.

Catalyst

An agent that enhances a reaction rate by providing a surface to lower Ea while remaining unaltered.

what is the exact free energy value ΔG for the hydrolysis of ATP into ADP +P{i}?

ΔG = -7.3 kcal/mol

The input of heat increases the kinetic energy of average molecules, but why is this thermal activation not useful in cells?

Cells are isothermal and must maintain constant temperature

how does a catalyst effectively reduce the required activation energy

It binds reactants on a surface and brings them close together

While a reaction can take place due to favorable thermodynamics, ____________ make the difference by ensuring a reaction will take place.

Enzymes

Even though the hydrolysis of ATP is thermodynamically feasible, ATP dissolved in water remains completely stable for several ____________.

days

the peak configuration that sits at the highest point of the energy curve is called the ____________ state.

transition

When a catalyst lowers the activation energy of a reaction, the thermodynamic value labeled as ____________ remains completely unchanged.

ΔGº'(free energy change)

which of the following is a basic property shared by all catalysts?

They form transient, reversible complexes with substrate molecules.

While most enzymes are known to be proteins, recent discoveries show that certain RNA molecules also possess catalytic activity. What are these specialized RNA catalysts called?

Ribozymes

an enzyme like hexokinase transfers a functional phosphoryl group from ATP to glucose. Into which of the six major classes is this enzyme categorized?

Transferases

The slide indicates that coenzymes are small organic molecules that function as cofactors for catalytic activity. What are coenzymes specifically derived from?

Vitamins

Oxidoreductases

Enzymes that catalyze oxidation-reduction reactions involving electron transfer

Transferases

Enzymes that transfer functional groups from one molecule to another

Hydrolases

Enzymes that use a water molecule to catalyze the hydrolytic cleavage of one molecule into two molecules

Lyases

Enzymes that catalyze the removal of a group from a molecule, or the addition of a group to a molecule, without using water

Isomerases

Enzymes that move a functional group within a single molecule to alter its geometric structure

Ligases

Enzymes that join two separate molecules together to form a single molecule

Ribozymes

RNA molecules that possess catalytic activity instead of proteins

An enzyme called alcohol dehydrogenase facilitates the conversion of ethanol to acetaldehyde by transferring electrons to reduce NAD+ into NADH. Into which major class is this enzyme categorized?

Oxidoreductases

Hexokinase is an enzyme that catalyzes the phosphorylation of glucose into glucose-6-phosphate by physically moving a terminal functional phosphoryl group from an ATP molecule over to the sugar. This mechanism classifies hexokinase as a:

transferase

The enzyme glucose-6-phosphatase uses a water molecule to split glucose-6-phosphate down into individual pieces of glucose and inorganic phosphate. Any enzyme that drives the hydrolytic cleavage of one molecule into two distinct molecules belongs to which class?

hydrolases

Pyruvate decarboxylase removes a carboxyl group from a pyruvate molecule to generate acetaldehyde and carbon dioxide without relying on a water molecule. Enzymes that remove a group from, or add a group to, a molecule in this manner are classified as:

lyases

Maleate isomerase catalyzes the conversion of maleate into fumarate via a cis-trans geometric restructuring. Because it changes the spatial arrangement of a functional group strictly within the same single molecule, it is classified as an:

isomerase

The enzyme pyruvate carboxylase adds a molecule of CO2 to pyruvate to join them together and produce oxaloacetate. An enzyme that couples or joins two separate molecules together to synthesize a single compound is classified as a:

ligase

While organic catalysts made of protein chains are called enzymes, catalytic molecules made entirely out of RNA chains are classified as ____________.

ribozymes

In structural biology, an enzyme like ribonuclease P behaves as an RNA-based catalyst that selectively cuts and cleaves ____________ precursors to produce functional, mature RNA pieces.

transfer RNA(tRNA)

If you are classifying an enzyme that transfers electrons or handles general oxidation-reduction reactions, you are identifying a member of the ____________ class.

Oxidoreductases

In three-dimensional space, the active site pocket of an unfolded enzyme can contain distant sequence segments—such as Glutamate at position 35 and Aspartate at position 52—that are successfully brought close together only when the protein becomes completely ____________.

folded

Enzymes match target configurations with strict chemical selectivity; for instance, succinate dehydrogenase will smoothly process its true chemical complement fumarate, but it completely rejects the structural isomer ____________.

maleate

prosthetic groups

Nonprotein cofactors that are usually metal ions or small organic molecules tightly needed for catalytic activity

An enzyme allows a reaction to reach its chemical equilibrium much faster by changing the rate at which equilibrium is achieved, but it does not change the ____________ of the equilibrium.

position

Enzyme specificity

The ability of an enzyme to select specific substrates due to the unique shape and chemistry of its active site pocket

Active site

A specific groove or pocket formed by the three-dimensional folding of a protein containing a characteristic cluster of amino acids where substrates bind and catalysis takes place.

pH optimum

specific pH level where an enzyme's rate of reaction is highest because ionizable groups on both the enzyme and substrate are in their most favorable forms for reactivity.

Pepsin pH baseline

A stomach enzyme adapted to highly acidic environments, displaying a sharp reaction rate peak at an optimal pH of about 2.0

Trypsin pH baseline

An intestinal enzyme adapted to mildly basic environments, displaying a sharp reaction rate peak at an optimal pH near 8.0.

Cofactors

Nonprotein components needed for catalytic activity, frequently serving as electron acceptors to satisfy nutritional requirements for trace minerals and vitamins.

Coenzymes

Small organic prosthetic groups that are directly derived from vitamins.

Prosthetic groups

Tightly bound enzyme cofactors that typically consist of metal ions or small organic molecules.

Three basic properties of catalysts

Lower Ea, form transient/reversible complexes with substrates, change the rate of achieving equilibrium without altering the equilibrium position.

Because of the shape and chemistry of the active

site, enzymes have a very high ___________ ______________

substrate specificity

Induced-fit model

A model of enzyme-substrate interaction where the binding of a substrate induces a conformational shape change in the enzyme.

Induced conformational change

shape change that brings needed amino acid side chains into the active site, including those that are not initially nearby.

Active site holding force

Specific noncovalent interactions that hold a substrate in place once it enters the active site pocket.

Optimal substrate positioning

Alignment driven by noncovalent active site interactions that position the substrate optimally for catalysis and distinguish the real substrate from similar molecules.

X-ray diffraction evidence for induced-fit

Structural observation showing that enzymes bound to a substrate have different shapes compared to those same enzymes in the absence of substrate binding.

Bond distortion

An activation mechanism that structurally strains a chemical bond, making it more susceptible to catalytic attack.

Proton transfer

An activation mechanism that increases the chemical reactivity of a substrate by donating or accepting protons.

Electron transfer

An activation mechanism resulting in the temporary formation of covalent bonds between the enzyme and the substrate.

Irreversible inhibitors

bind to the enzyme covalently, causing permanent loss of catalytic activity, and are generally toxic to cells ( heavy metals, nerve gas poisons, drugs)

Reversible inhibitors

Inhibitors that bind to enzymes noncovalently and can freely dissociate from the enzyme molecule.

Reversible inhibition equilibrium

A dynamic biological balance (E+I⇌EI) where available enzyme depends on inhibitor concentration and how easily the enzyme and inhibitor dissociate.

Competitive inhibition

A type of reversible inhibition where both the inhibitor and substrate compete to bind to the exact same active site on the enzyme.

Competitive substrate dependence

A trait of competitive inhibition where the amount of available active enzyme depends directly on the concentration of the substrate.

Noncompetitive inhibition

A type of reversible inhibition where the inhibitor and substrate bind to completely different sites on the enzyme.

Noncompetitive substrate independence

A trait of noncompetitive inhibition where the amount of available active enzyme is completely independent of the concentration of the substrate.

Which of the following physical observations explicitly favors the induced-fit model for enzyme-substrate interactions over older, rigid models?

X-ray diffraction shows that enzymes bound to a substrate have different shapes from those same enzymes in the absence of substrate binding.

which mechanism explicitly results in the temporary formation of covalent bonds between the enzyme and the substrate molecule?

Electron transfer

What chemical characteristic and functional outcome defines an irreversible inhibitor

binds the enzyme covalently, causing a permanent loss of catalytic activity.

When a noncompetitive inhibitor binds to its unique regulatory site, how does it physically prevent the formation of reaction products?

It binds to a different site and distorts the enzyme, inhibiting substrate binding or reducing catalytic activity.

The visual model demonstrating induced-fit depicts an enzyme altering its three-dimensional structure around an incoming substrate molecule of ____________

D-glucose

Heavy metal ions, nerve gas poisons, and some insecticides serve as classic real-world examples of ____________ inhibitors.

irreversible

In the case of competitive inhibition, the binding of an inhibitor directly prevents substrate binding, meaning that available active enzyme depends heavily on the concentration of the ____________.

substrate

The fundamental chemical equation representing the dynamic, noncovalent binding and release of a generic reversible inhibitor is written as ____________.

E+I⇌EI

Substrate activation can be achieved via three common mechanisms: proton transfer, electron transfer, and ____________.

bond distortion

According to the noncompetitive diagram details, the amount of available active enzyme remains entirely ____________ of the concentration of the substrate.

independent

3 types of substrate activation mechanisms

proton transfer, electron transfer, bond distortion

Substrate-level regulation

Regulation that depends directly on the interactions of substrates and products with an enzyme.

Allosteric regulation:

The single most important control mechanism in cells where enzyme rates are adjusted by molecules other than reactants and products.

Allosteric conformations

The two structural shapes of an allosteric enzyme; one has a high affinity for substrates, and the other does not.

Catalytic subunit

The specific subunit of an allosteric enzyme that contains the active site.

Regulatory subunit

The specific subunit of an allosteric enzyme that contains the allosteric site.

Allosteric inhibition

A process where an inhibitor binds to a regulatory site and stabilizes an enzyme in its low-affinity form.

Allosteric activation

A process where an activator binds to a regulatory site and stabilizes an enzyme in its high-affinity form.

Feedback inhibition

A control loop where the final end-product of a metabolic pathway negatively regulates an earlier enzyme step in that same pathway.

Covalent Modification

The regulation of an enzyme's activity through the reversible addition or removal of specific chemical groups.

Kinase

An enzyme that adds a phosphate group to a molecule during phosphorylation.

Phosphatase

An enzyme that removes a phosphate group from a molecule during dephosphorylation.

Glycogen phosphorylase b

The inactive, dephosphorylated form of the glycogen-cleaving enzyme.

Glycogen phosphorylase a

The active, phosphorylated form of the glycogen-cleaving enzyme.

Proteolytic cleavage

An irreversible mechanism that activates an enzyme by physically removing a part of its polypeptide chain.

Zymogens

Inactive precursor forms of enzymes that are synthesized and stored until activated by proteolytic cleavage.

According to the principles of substrate-level regulation, what direct effect do high levels of a reaction's product have on its enzyme's reaction rate?

Increased product levels lead to lower reaction rates.

In an allosteric enzyme complex containing multiple polypeptide pieces, where are the active sites and allosteric sites located?

Active sites are on the catalytic subunits, and allosteric sites are on the regulatory subunits.

methylation and demethylation

the addition or removal of a methyl group

phosphorylation and dephosphorylation

addition/removal of phosphate groups through the action of protein kinases/phosphatases

acetylation/deacetylation

Addition or removal of an acetyl group

Irreversible covalent activation via proteolytic cleavage is used to control volatile physiological processes. According to the slides, what are the primary examples of these systems?

Proteolytic enzymes in the pancreas, the coagulation cascade, and the complement cascade.

Suppose that you extracted an enzyme, enzyme X, from a bacterium. You found that the addition of a protease to the solution containing enzyme X and its substrate increased the rate of reaction. What is the best explanation for this observation?

Enzyme X has been activated by proteolytic cleavage.

Phosphorylation by an enzyme called phosphorylase kinase converts inactive glycogen phosphorylase b into its active form, which is labeled as ____________.

glycogen phosphorylase a

Unlike reversible phosphorylation or allosteric interactions, activation by proteolytic cleavage is completely ____________.

irreversible

An enzyme subject to allosteric ____________ is inactive in its uncomplexed form and requires a regulator to stabilize its high-affinity conformation.

activation

Feedback inhibition is highly necessary because it is not in the best interests of a cell for enzymatic reactions to proceed continuously at their ____________ rate.

maximum