Chapter Twenty One Enzymes and Vitamins. Ch 21 | # 2 of 47 Catalysts for biological reactions Proteins Lower the activation energy Increase the rate of.

Chapter Chapter Twenty OneTwenty One

Enzymes and Vitamins

Ch 21 | # 2 of 47

• Catalysts for biological reactions• Proteins• Lower the activation energy• Increase the rate of reaction• Have specific shapes that match

the shapes of reactants • Activity lost if denatured• May be simple proteins or complex• May contain cofactors such as metal ions or organic

(vitamins)

Enzymes

Ch 21 | # 3 of 47

• End in –ase• Identifies a reacting substance

sucrase – reacts sucroselipase - reacts lipid

• Describes function of enzymeoxidase – catalyzes oxidationhydrolase – catalyzes hydrolysis

• Common names of digestion enzymes still end –inpepsin, trypsin

Names of Enzymes

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Class Reactions catalyzed• Oxidoreductoases oxidation-reduction• Transferases transfer group of atoms• Hydrolases hydrolysis• Lyases add/remove atoms

to/from a double bond• Isomerases rearrange atoms• Ligases combine molecules

using ATP

Classification of Enzymes

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• Oxidoreductoasesoxidases - oxidizereductases – reduce

• Transferasestransaminases – transfer amino groupskinases – transfer phosphate groups

• Hydrolasesproteases - hydrolyze peptide bondslipases – hydrolyze lipid ester bonds

• Lyases

carboxylases – add CO2

hydrolases – add H2O

Examples of Enzyme Classification

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Enzyme Structure

• The shape/structure of enzymes is related to their functions– Simple enzymes

• Enzymes that consist only of protein

– Conjugated enzymes• Enzymes that consist of protein and a nonprotein part• Apoenzyme + cofactor = holoenzyme• Coenzyme: small organic molecule that serves as a cofactor in

a conjugated enzyme (needed to prepare the active site for catalytic activity)

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Vitamins

• Organic compounds that are essential for the proper functioning of the human body– Many function as cofactors

• Cannot be synthesized by the human body• Must be obtained from dietary sources• Two main classes:

– Water-soluble– Fat soluble

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Water-Soluble Vitamins

• Soluble in aqueous solutions• Used as cofactors by many enzymes• Not store in the body

• Vitamin C• Vitamin B

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Fat-Soluble Vitamins

• Vitamins A, D, E, and K• Soluble in lipids, but not in aqueous solutions• Important in vision, bone formation, antioxidants,

and blood clotting• Stored in the body

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• An enzyme binds a substrate in a region called the active site– Only certain substrates can fit the active site– Amino acid R groups in the active site help substrate bind and

align correctly

• Enzyme-substrate complex forms• Substrate reacts to form product• Product is released

Enzyme Action

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The active site of an enzyme can be a crevice-like region formed as a result of the protein’s secondary and tertiary structural characteristics.

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Enzyme Specificity

• Enzymes may recognize and catalyze:– 1. A single substrate: Absolute Specificity

• Example: Urease (only catalyzes the hydrolysis of urea)

– 2. A single stereoisomer: Stereochemical Specificity

• Example: L-amino-acid oxidase (catalyzes the oxidation of L-amino acids, but not D-amino acids)

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Enzyme Action: Lock and Key Model

• In the lock and key model of enzyme action:– The active site has a rigid shape– Only substrates with the matching shape can fit– The substrate is a key that fits the lock of the active site

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Enzyme Action: Lock and Key Model

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+ +

E + S ES complex E + P

S

P

P

S

Lock and Key Model

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Enzyme Specificity

• Enzymes may recognize and catalyze:– 3. A group of similar substrates: Group

Specificity• Example: Hexokinase (adds a phosphate to

hexoses)

– 4. A particular type of bond: Linkage Specificity• Example: Chymotrypsin (catalyzes the hydrolysis of

peptide bonds)

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• Enzyme structure flexible, not rigid• Enzyme and active site adjust shape to bind substrate• Increases range of substrate specificity• Shape changes also improve catalysis during reaction

Enzyme Action: Induced Fit Model

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Enzyme Action

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E + S ES complex E + P

S

P

P

SS

Enzyme Action: Induced Fit Model

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Enzyme Activity

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• Little activity at low temperature

• Rate increases with temperature

• Most active at optimum temperatures (usually 37°C in humans)

• Activity lost with denaturation at high temperatures

Factors Affecting Enzyme Action: Temperature

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• Maximum activity at optimum pH

• Narrow range of activity• Most lose activity in low or

high pH

• Why is one pH better than another?– R groups of amino acids have

proper charge at certain pH values

– Tertiary structure of enzyme is correct

Factors Affecting Enzyme Activity: pH

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• Increasing substrate concentration increases the rate of reaction (enzyme concentration is constant)

• Maximum activity reached when all of enzyme combines with substrate

Factors Affecting Enzyme Activity: Substrate Concentration

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Factors Affecting Enzyme Activity: Enzyme Concentration

• The rate of reaction increases as enzyme concentration increases (at constant substrate concentration)

• At higher enzyme concentrations, more substrate binds with enzyme

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Inhibitors • Molecules that cause a loss of catalytic activity• Change the protein structure of an enzyme to prevent

substrates from fitting into the active sites• May be “competitive” or “noncompetitive”• Some effects are irreversible

Enzyme Inhibition

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A competitive inhibitor• Has a structure similar to substrate• Occupies active site• Competes with substrate for active site• Has effect reversed by increasing substrate concentration

Competitive Inhibition

http://www.eccentrix.com/members/chempics/Slike/Enzyme/2Competitive_inhibition.jpg

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A noncompetitive inhibitor• Does not have a structure like substrate• Binds to the enzyme but not active site• Changes the shape of enzyme and active site• Substrate cannot fit altered active site• No reaction occurs• Effect is not reversed by adding substrate• Substrate activity is restored when inhibitor is no

longer bonded to the enzyme

Noncompetitive Inhibition

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Heavy metal poisoning is an example of

noncompetitive inhibition of an enzyme.

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Irreversible Inhibition

• In irreversible inhibition, a substance destroys enzyme activity by bonding with R groups at the active site

• Inhibitor permanently blocks substrate binding– One of the ways antibiotics kill bacteria

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Structures of selected sulfa drugs in use today as antibiotics.

Sulfa Drugs

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Regulating Enzyme Activity

• Four main mechanisms to regulate enzyme activities– Genetic Control– Feedback Control– Zymogen Activation– Allosteric Regulation

• Activation – Positive Regulation• Deactivation – Negative Regulation

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Feedback Control

• In feedback control:– A product of a reaction acts as a negative regulator– An end product binds with the first enzyme in a

sequence when sufficient product is present

E1 E2 E3

A B C D

Inhibition of enzyme 1 by product D

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Zymogens

– Inactive forms of enzymes– Activated when one or more peptides are removed– Example: Proinsulin is converted to insulin by removing a small

peptide chain– Digestive enzymes are produced in one organ as zymogens, but

not activated until they are needed; Ex. trypsinogen / trypsin

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Allosteric Enzymes

• An enzyme with two or more protein chains (quaternary structure) and two kinds of binding sites (substrate and regulator)– Activity is influenced by “regulators” (found or produced in cells

normally)

• Positive regulator– Enhances the binding of substrate and accelerates the rate of

reaction

• Negative regulator– Prevents the binding of the substrate to the active site and slows

down the rate of reaction

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Enzymes and Vitamins

• Levels of enzymes in blood used as a diagnostic tool.

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Diagnostic Enzymes

• The levels of diagnostic enzymes determine the amount of damage in tissues

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Enzymes and Vitamins