Biology 1710 [Chapter 6] Metabolism 6.5 Enzymes

Induced Fit

This model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme's structure that confirms an ideal binding arrangement between the enzyme and the substrate's transition state. This ideal binding maximizes the enzyme's ability to catalyze its reaction.

Enzymes

the special molecules that catalyze biochemical reactions

The local environment's pH can also affect enzyme function. Active site amino acid residues have their own acidic or basic properties that are optimal for catalysis. These residues are sensitive

to changes in pH that can impair the way substrate molecules bind. Enzymes are suited to function best within a certain pH range, and, as with temperature, extreme environmental pH values (acidic or basic) can cause enzymes to denature.

High temperatures will eventually cause enzymes, like other biological molecules,

to denature

The fact that active sites are so perfectly suited to provide specific environmental conditions also means that they are subject

to local environmental influences.

The appropriate region (atoms and bonds) of one molecule is juxtaposed

to the other molecule's appropriate region with which it must react.

Catalyst

A substance that helps a chemical reaction to occur

Metabolism Control Through Enzyme Regulation

A variety of mechanisms ensure that this does not happen. Cellular needs and conditions vary from cell to cell, and change within individual cells over time. The required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and functionality of different enzymes.

Induced-Fit Model

According to the induced-fit model, both enzyme and substrate undergo dynamic conformational changes upon binding. The enzyme contorts the substrate into its transition state, thereby increasing the reaction's rate.

When an allosteric inhibitor binds to an enzyme,

All active sites on the protein subunits change slightly such that they bind their substrates with less efficiency

Allosteric Activators and Inhibitors Model

Allosteric inhibitors modify the enzyme's active site so that substrate binding is reduced or prevented. In contrast, allosteric activators modify the enzyme's active site so that the affinity for the substrate increases

Due to this jigsaw puzzle-like match between an enzyme and its substrates (which adapts to find the best fit between the transition state and the active site)

Enzymes are known for their specificity. The "best fit" results from the shape and the amino acid functional group's attraction to the substrate. There is a specifically matched enzyme for each substrate and, thus, for each chemical reaction; however, there is flexibility as well.

Molecular Regulation of Enzymes

Enzymes can be regulated in ways that either promote or reduce their activity. There are many different kinds of molecules that inhibit or promote enzyme function, and various mechanisms exist for doing so.

Activation Energy Diagram

Enzymes lower the reaction's activation energy but do not change the reaction's free energy

Enzyme Compartmentalization

In eukaryotic cells, molecules such as enzymes are usually compartmentalized into different organelles. This allows for yet another level of regulation of enzyme activity. Enzymes required only for certain cellular processes are sometimes housed separately along with their substrates, allowing for more efficient chemical reactions.

Allosteric inhibition

More than one polypeptide comprise most allosterically regulated enzymes, meaning that they have more than one protein subunit.

Enzymatic action can aid

The activation energy required for reactions

Substrate Specificity

The chemical reactants to which an enzyme binds are the enzyme's substrates

Enzyme Active Site

The location within the enzyme where the substrate binds This is where the "action" happens

In certain cellular environments, environmental factors like pH and temperature partly control enzyme activity thus.....

There are other mechanisms through which cells control enzyme activity and determine the rates at which various biochemical reactions will occur.

Dietary Vitamins Diagram

Vitamins are important coenzymes or precursors of coenzymes, and are required for enzymes to function properly. Multivitamin capsules usually contain mixtures of all the vitamins at different percentages.

In some cases of enzyme inhibition, an inhibitor molecule is similar enough to a substrate that it can bind to the active site and simply block the substrate from binding.

When this happens, the enzyme is inhibited through competitive inhibition

Some inhibitor molecules bind to enzymes in a location where their binding induces

a conformational change that reduces the enzyme's affinity for its substrate. This type of inhibition is an allosteric inhibition

Denature

a process that changes the substance's natural properties.

Two substrates may come together to create one larger molecule. Two reactants might also enter

a reaction, both become modified, and leave the reaction as two products.

There may be one or more substrates, depending on the particular chemical reaction. In some reactions,

a single-reactant substrate breaks down into multiple products

The unique combination of amino acid residues, their positions, sequences, structures, and properties, creates

a very specific chemical environment within the active site. This specific environment is suited to bind, albeit briefly, to a specific chemical substrate (or substrates).

Therefore, enzyme function is, in part, regulated by an

abundance of various cofactors and coenzymes, which the diets of most organisms supply

Finally, enzymes can also lower activation energies by taking part in the chemical reaction itself. The amino acid residues can provide certain ions or chemical groups that

actually form covalent bonds with substrate molecules as a necessary step of the reaction process.

However, increasing or decreasing the temperature outside of an optimal range can

affect chemical bonds within the active site in such a way that they are less well suited to bind substrates.

Producing both amino acids and nucleotides is controlled through feedback inhibition. Additionally, ATP is an

allosteric regulator of some of the enzymes involved in sugar's catabolic breakdown, the process that produces ATP.

Noncompetitive inhibition

an inhibitor molecule binds to the enzyme in a location other than the active site, called an allosteric site, but still manages to prevent substrate binding to the active site

Some vitamins are precursors to coenzymes

and others act directly as coenzymes

This complex lowers the reaction's activation energy

and promotes its rapid progression in one of many ways.

The most common sources of coenzymes

are dietary vitamins

Cofactors

are inorganic ions such as iron (Fe++) and magnesium (Mg++). One example of an enzyme that requires a metal ion as a cofactor is the enzyme that builds DNA molecules, DNA polymerase, which requires a bound zinc ion (Zn++) to function.

Coenzymes

are organic helper molecules, with a basic atomic structure comprised of carbon and hydrogen, which are required for enzyme action

Almost all enzymes

are proteins, comprised of amino acid chains, and they perform the critical task of lowering the activation energies of chemical reactions inside the cell

Competitive inhibition

because an inhibitor molecule competes with the substrate for active site binding

Allosteric activators

bind to locations on an enzyme away from the active site, inducing a conformational change that increases the affinity of the enzyme's active site(s) for its substrate(s).

Many enzymes don't work optimally, or even at all, unless

bound to other specific non-protein helper molecules, either temporarily through ionic or hydrogen bonds or permanently through stronger covalent bonds

Vitamin C is a coenzyme for multiple enzymes that take part in

building the important connective tissue component, collagen.

Enzymes lower the activation energy of chemical reactions

by binding to the reactant molecules, and holding them in such a way as to make the chemical bond-breaking and bond-forming processes take place more readily

An important step in breaking down glucose to yield energy is

catalysis by a multi-enzyme complex scientists call pyruvate dehydrogenase

Enzymes do NOT

change the reaction's ∆G. In other words, they do not change whether a reaction is exergonic (spontaneous) or endergonic. This is because they do not change the reactants' or products' free energy. They only reduce the activation energy required to reach the transition state

Binding to these molecules promotes optimal conformation and function for their respective enzymes

cofactors and coenzymes

Two types of helper molecules are

cofactors and coenzymes

The enzyme-substrate complex can lower the activation energy by

contorting substrate molecules in such a way as to facilitate bond-breaking, helping to reach the transition state.

It is true that increasing the environmental temperature generally

increases reaction rates, enzyme-catalyzed or otherwise.

Feedback Inhibition in Metabolic Pathways

involves using a reaction product to regulate its own further production (Figure 6.21). The cell responds to the abundance of specific products by slowing down production during anabolic or catabolic reactions. Such reaction products may inhibit the enzymes that catalyzed their production through the mechanisms that we described above.

Feedback Inhibition in Metabolic Pathways Diagram

involves using a reaction product to regulate its own further production (Figure 6.21). The cell responds to the abundance of specific products by slowing down production during anabolic or catabolic reactions. Such reaction products may inhibit the enzymes that catalyzed their production through the mechanisms that we described above.

Pyruvate dehydrogenase

is a complex of several enzymes that actually requires one cofactor (a magnesium ion) and five different organic coenzymes to catalyze its specific chemical reaction.

When an enzyme binds its substrate,

it forms an enzyme-substrate complex.

Different properties characterize each residue. These can be

large or small, weakly acidic or basic, hydrophilic or hydrophobic, positively or negatively charged, or neutral.

Alternatively, ADP serves as a positive allosteric regulator (an allosteric activator) as a positive allosteric regulator (an allosteric activator) for some of the same enzymes that ATP inhibits. Thus, when relative ADP

levels are high compared to ATP, the cell is triggered to produce more ATP through sugar catabolism.

On a basic level, enzymes promote chemical reactions that involve

more than one substrate by bringing the substrates together in an optimal orientation.

If too much ATP were present in a cell

much of it would go to waste.

Since enzymes are proteins, there is a unique combination

of amino acid residues (also side chains, or R groups) within the active site

Another way in which enzymes promote substrate reaction is by creating an

optimal environment within the active site for the reaction to occur. Certain chemical reactions might proceed best in a slightly acidic or non-polar environment.

The enzyme will always return to its original state at the reaction's completion. One of enzymes' hallmark properties is that they

remain ultimately unchanged by the reactions they catalyze. After an enzyme catalyzes a reaction, it releases its product(s).

Remember that ATP is an unstable molecule that can

spontaneously dissociate into ADP and inorganic phosphate

When ATP is abundant

the cell can prevent its further production.

The activation energy required for many reactions includes

the energy involved in manipulating or slightly contorting chemical bonds so that they can easily break and allow others to reform.

Some inhibitor molecules bind to enzymes in a location where their binding induces a conformational change that reduces

the enzyme activity as it no longer effectively catalyzes the conversion of the substrate to product.

Examples of enzyme compartmentalization

the enzymes involved in the latter stages of cellular respiration, which take place exclusively in the mitochondria, and the enzymes involved in digesting cellular debris and foreign materials, located within lysosomes.

The chemical properties that emerge from the particular arrangement of amino acid residues within an active site create

the perfect environment for an enzyme's specific substrates to react

Since the rates of biochemical reactions are controlled by activation energy, and enzymes lower and determine activation energies for chemical reactions

the relative amounts and functioning of the variety of enzymes within a cell ultimately determine which reactions will proceed and at which rates. This determination is tightly controlled