chem 121 unit 5 enzymes
TRANSCRIPT
-
8/2/2019 CHEM 121 Unit 5 Enzymes
1/22
CHEM 121
Biochemistry for Nurses
Unit 5 - Enzymes
-
8/2/2019 CHEM 121 Unit 5 Enzymes
2/22
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.
-
8/2/2019 CHEM 121 Unit 5 Enzymes
3/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
4/22
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.
-
8/2/2019 CHEM 121 Unit 5 Enzymes
5/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
6/22
Enzyme
Substrate
Lock and Key Mechanism
-
8/2/2019 CHEM 121 Unit 5 Enzymes
7/22
Enzyme
Induced Fit Mechanism
Substrate
-
8/2/2019 CHEM 121 Unit 5 Enzymes
8/22
Enzyme
Substrate ENZYME
SUBSTRATE (ES)COMPLEX
Product
ENZYME
PRODUCT (EP)COMPLEX
Enzyme Complexes
-
8/2/2019 CHEM 121 Unit 5 Enzymes
9/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
10/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
11/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
12/22
-
8/2/2019 CHEM 121 Unit 5 Enzymes
13/22
-
8/2/2019 CHEM 121 Unit 5 Enzymes
14/22
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)
-
8/2/2019 CHEM 121 Unit 5 Enzymes
15/22
Factors affecting Reaction Rate
Substrate Concentration
-
8/2/2019 CHEM 121 Unit 5 Enzymes
16/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
17/22
Factors affecting Reaction Rate -
Temperature
-
8/2/2019 CHEM 121 Unit 5 Enzymes
18/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
19/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
20/22
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
-
8/2/2019 CHEM 121 Unit 5 Enzymes
21/22
Enzymes in Medicine
-
8/2/2019 CHEM 121 Unit 5 Enzymes
22/22
References
Lippincotts Illustrated Reviews:
Biochemistry. Editors: Pamela Champe,Richard Harvey. 3rd Edition.