CHEM 121 Unit 5 Enzymes

8/2/2019 CHEM 121 Unit 5 Enzymes

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CHEM 121

Biochemistry for Nurses

Unit 5 - Enzymes


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Introduction

Nearly all reactions in body catalyzed by

enzymes (i.e. enzymes speed upreactions; enzymes increase the rate ofreactions)

Enzymes increase the rate of reactionswithout themselves being ultimatelychanged

Most enzymes are proteins. Some RNA

can act as enzymes. They are calledribozymes.


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Classification of Enzymes Oxidoreductases catalyze oxidation-reduction

reactions Transferases catalyze reactions that involve

transfer of C, N or P-containing groups Hydrolases catalyze reactions that involve

cleavage of bonds by addition of water Lyases catalyze reactions that involve

cleavage of C-C, C-S and C-N bonds Isomerases catalyze reactions that involve

racemization of superimposable (mirror image)

isomers Ligases catalyze reactions that involve

formation of bonds between carbon and O, S, N


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Properties of Enzymes Active sites enzymes contain special cleft containing

amino acid side chains which create a 3D surface which is

complementary to that of a specific substrate. An enzyme-substrate (ES) complex is formed. ES is converted to EP(enzyme-product complex) which then dissociates toenzyme and product

Catalytic efficiency highly efficient ; 103 to 108 times

faster than uncatalyzed. The number of molecules ofsubstrate converted to product per enzyme molecule persecond is called the turnover number (usually 100 to1000) .

Specificity highly specific; interacts with one or a fewsubstrates; catalyzes only one type of chemical reaction

Regulation enzymes can be activated or inhibited sothat the rate of product formation responds to the needs ofthe cell.


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Cofactors some enzymes need to associate

with a non-protein co-factor in order to function. Metal ions (Zn2+, Fe2+)

Organic molecules known as co-enzymes, oftenderivatives of vitamins (NAD+, FAD+,co-enzyme A).

Location in the cell many enzymes arelocalized in specific organelles within the cell

isolate the reaction substrate or product from othercompeting reactions

provides a favorable environment for the reaction

organizes the thousands of enzymes present in the cell intopurposeful pathways.

Properties of Enzymes


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Enzyme

Substrate

Lock and Key Mechanism


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Enzyme

Induced Fit Mechanism

Substrate


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Enzyme

Substrate ENZYME

SUBSTRATE (ES)COMPLEX

Product

ENZYME

PRODUCT (EP)COMPLEX

Enzyme Complexes


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Enzyme Mechanism Note that all molecules have a certain amount of energy

Converting one molecule into another molecule is called areaction

Or (converting one group of molecules into another groupof molecules)

Consider the reaction glucose-6-phosphate (the reactant)

being converted to glucose-1-phosphate (the product).

H OH

O

4

CH2

OH

H

H H

OH OH

O

1

23

5

6

H

4

O

OP

-O

-

H OH

OH

4

CH2

O

H

H H

OH OH

O

1

23

5

6

H

O

OP

-O

-

4

phosphoglucomutase

Glucose-6-Phosphate Glucose-1-Phosphate


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Glucose-6-phosphate has a certain amount of energy andglucose-1-phosphate has a certain amount of energy

This can be represented on a graph which has progress ofthe reaction on the x axis and amount of energy on the yaxis

Before Glucose-6-phosphate (the reactant) can be

converted into Glucose-1-phosphate (the product),Glucose-6-phosphate is converted into an intermediateform where bonds are in the process of being broken andrearranged and reformed.

This intermediate form is called the transition state and it

has a higher energy than either the reactants or products.

Enzyme Mechanism


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The reactants must gain sufficient energy to

reach the transition state in order to be changedinto products. This is like climbing over a hill toget from one side to the next.

This energy is called the activation energy.

With respect to how the enzyme works, it lowersthe activation energy, so that the reactants needto gain less energy in order to be changed intothe transition state.

Therefore, more molecules of reactants can bechanged into product in a certain amount of time(this is called increasing the rate of the reaction)

Enzyme Mechanism


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Factors affecting Reaction Rate

Substrate Concentration

Substrate concentration

Rate of a reaction (v) is the number of substratemolecules converted to product per unit time (e.g.moles product formed per minute).

The rate of an enzyme-catalyzed reaction increases withsubstrate concentration until a maximum rate is reached(please see graph)

When the reaction rate levels off at high substrateconcentration this is due to all enzyme moleculesbinding sites being filled up with substrate, so the

reaction cannot go any faster (please see graph)


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Factors affecting Reaction Rate

Substrate Concentration


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Temperature

Increasing temperature increases the rate ofthe reaction until a peak rate is reached.

This is because an increased number ofmolecules have sufficient energy to get to the

transition state Further increase of temp causes a decrease in

reaction rate due to denaturation (breakdown)of the enzyme. Remember that enzymes are mostly proteins. The

unravelling of the tertiary or quaternary structure ofproteins into primary structure is called denaturation.The protein is said to have been denatured.

Factors affecting Reaction Rate -

Temperature


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Factors affecting Reaction Rate -

Temperature


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pH Ideally enz and substrate have specific chemical groups

in an ionized or unionized state in order to interact.

An e.g of an ionized group is NH3+

An e.g of an un ionized group is NH2.

Therefore changes in conc of H+ ions may result in

changes in ionization state. For example the presence ofhigh levels of H+ ions (acid conditions) will causeconversion of NH

2into NH

3+.

Such changes in important chemical groups will preventthe enzyme from functioning properly.

Changes in pH also causes denaturation of the enz.Because of changes in the ionic state of the amino acidside chains

Factors affecting Reaction Rate - pH


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Enzymes in Medicine Enzyme inhibitors

Penicillin, amoxylin inhibit enzymes of the bacterial cell wall

synthesis Diagnosis

Damaged tissues can be detected by abnormally elevatedplasma levels of enzymes which are normally present in thecells of those tissues and are specific to those tissues. This isdue to damage of the cells of those tissues and release of

enzymes present in the cell into the plasma. Alanine aminotransferase (ALT) elevated in plasma means

possible damage to hepatic tissue Creatine kinase (CK), also known as creatine phosphokinase

(CPK)

Isoenzymes CK-MM, CK-BB and CK-MB. increased levels after myocardial infarction 4 to 8 hrs after onset of chest pain Peaks at 24 hrs after onset of pain


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Lactate dehydrogenase (LDH) exists as isoenzymes in differentorgans

LDH-1 in the heart and RBCs LDH-2 in the reticuloendothelial system LDH-3 in the lungs LDH-4 in the kidneys, placenta and pancreas

LDH-5 in the liver and striated muscle

Increased levels of LDH1 over LDH2 indicates myocardialinfarction

Increased levels used to detect cancer, meningitis,encephalitis, acute pancreatitis, and HIV

NOTE: Newer markers of angina and myocardial infarction areelevated plasma levels of two proteins which are involved incontraction of heart muscle tissue:Troponin T and Troponin I

Enzymes in Medicine


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Enzymes in Medicine


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References

Lippincotts Illustrated Reviews:

Biochemistry. Editors: Pamela Champe,Richard Harvey. 3rd Edition.

Documents

CHEM 121 Unit 5 Enzymes