Enzymes and Biological Regulation

Enzyme Characteristics • Enzymes are proteins that catalyze chemical reactions. They speed up chemical reactions by lowering activation energies.

Enzyme Characteristics, cont. • Most enzymes are proteins. • Enzymes are specific in the type of reactions they catalyze. 1. Absolute specificity – acts only on one substance. 2. Relative specificity – acts on structurally related substances. 3. Stereochemical specificity – distinguishes between stereoisomers.

Classifying and Naming Enzymes

Enzyme Characteristics, cont. • Their activity can be regulated. • There are approximately 3000 enzymes per cell • Common enzymes we have seen: 1. Lactase – digests lactose into glucose and fructose 2. Maltase – hydrolysis of maltose to glucose for yeast alcohol production. 3. Protease – breaks peptide linkages to form protein segments in amino acid sequencing.

Classifying and Naming Enzymes, cont.

• A substrate is the substance that undergoes a chemical change catalyzed by an enzyme. • Enzyme names are based on the substrate or type of reaction and adding –ase ending

Reference

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Enzymatic Processes • All enzymes have an active site – the location on the enzyme where a substrate binds and catalysis occurs. • Enzymes complex with the substrate and the chemical reaction proceeds.

Enzymatic Processes, cont. The active site of an enzyme is usually a crevice-like region formed as the result of the protein’s secondary and tertiary structural characteristics.

Enzymatic Processes, cont. There are two main theories on active sites: 1. Lock-and-key theory – the substrate has a shape that exactly fits the active site. This explains enzyme specificity.

Enzymatic Processes, cont.

2. Induced-fit theory – the conformation of the active site changes to accommodate an incoming substrate.

Enzyme Regulation Enzyme regulation refers to the biological processes that control the ability of enzymes to catalyze reactions. Controls include: 1.Presence of cofactors 2.Inhibition 3.Induction/degradation 4.Modulation (Allosteric Regulation) 5.Zymogen activation

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Enzyme Regulation, cont. 1. Enzyme Cofactors •Some enzymes require a second substance present (cofactor) in order to be active. •Cofactors can be metal ions or a nonprotein molecule –If the cofactor is an organic molecule, the cofactor is called a coenzyme. •Coenzymes are often derived from vitamins.

Enzyme Regulation, cont. 2. Enzyme Inhibition •Inhibitors decrease enzyme activity. •Irreversible inhibitors covalently bond with the enzyme and render it inactive.
Many poisons are irreversible inhibitors. Examples: CN-, Hg2+, Pb2+
Some antibiotics are irreversible inhibitors.

Enzyme Inhibition, cont. Competitive inhibition can be reversed by increasing substrate concentration (LeChatlier’s principle).

Enzyme Cofactors, cont. • An apoenzyme is the catalytically inactive protein formed by the removal of the cofactor.

• The biologically active protein formed by the presence of a cofactor is called a haloenzyme –The ES complex can not exist with out the cofactor.

Enzyme Inhibition, cont. • Reversible inhibitors reversibly bind with enzymes. • Types of reversible inhibitors: 1. Competitive reversible inhibitors - compete with substrate for binding at active site. 2. Noncompetitive reversible inhibitors - bind to the enzyme at a location other than the active site. (form of modulation)

Enzyme Inhibition, cont. Substrate concentration doesn’t affect inhibitor action in non-cometitive inhibition.

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Enzyme Inhibition, cont. Heavy metal poisoning is an example of noncompetitive inhibition of an enzyme.

Enzyme Inhibition, cont. •Feedback inhibition is a form of competitive inhibition where the molecule produced by the catalysis of many reactions results in an inhibitor to an earlier catalyzed reaction.

Enzyme Regulation, cont. 3.Induction/ Degradation • Form of Genetic control • Induction refers to the body’s synthesis of enzymes in response to cellular need. • Degradation is the subsequent hydrolysis of enzymes to amino acid or peptide residues. Biological systems usually utilize induction/degradation for enzymes needed only for temporary use due to the inefficiency of the control.

Induction/ Degradation, cont.

Enzyme Regulation, cont.

• Example of Enzyme Induction:

4. Modulation

– Synthesis of β-galactosidase in bacterium. – Escherichia coli (E. coli) produce β-galactosidase as needed for the hydrolysis. – When there is an absence of lactose, the bacteria stops producing the enzyme

• Modulation, also called allosteric regulation, refers to the binding of a chemical species to a binding site other than the active site to control enzyme activity •Enzymes containing a secondary binding site, or modulator binding site, are called allosteric enzymes. •Modulation may be positive or negative •Positive modulators increase activity by changing the shape of the active site to allow the ES complex.

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Modulation, cont.

•Negative modulators (seen here) decrease activity by changing the shape of the active site to prevent the ES complex.

Enzyme Regulation, cont. 5. Zymogen activation • Zymogens – an inactive precursor (proenzyme) of an enzyme. – Some enzymes are stored as inactive zymogens. – Released when needed and activated at the location where the reaction occurs by either an activation agent or by autoactivation.

Zymogen activation, cont. •An example of activation occurs when chymotrypsinogen (in the pancreas) is activated by the presence of trypsin in the small intestine resulting in the chymotrypsin enzyme.

Modulation, cont.

•Feedback inhibition is an example of a modulator decreasing an allosteric enzyme’s activity.

Zymogen activation, cont. •Autoactivation can also occur as the zymogen is introduced to a chemical species or physiological environment that allows the formation of the proteins native state. •Activation can also occur in the presence of a chemical species due to the resulting changes in the IM forces and 3o,4o structure.

Zymogen activation, cont. •Activation may also occur by the addition or removal of a section of protein catalyzed by an activation enzyme (or activation agent)

* [notice the –ogen suffix of the proenzme]

Chymotrypsinogen

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Zymogen activation, cont.

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