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23 Chapter 23
Enzymes
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23 Enzyme Catalysis
Enzyme: a biological catalyst. With the exception of some RNAs that catalyze their own self-cleavage, all enzymes are proteins. Enzymes can increase the rate of a reaction by a factor of 109 to 1020 over an uncatalyzed reaction. Some catalyze the reaction of only one compound.
( NH2 )C=O + H2 O ureas e Urea 2NH3 + CO2
Others are stereospecific; for example, enzymes that catalyze the reactions of only L-amino acids. Others catalyze reactions of specific types of compounds or bonds; for example, trypsin that catalyzes hydrolysis of peptide bonds formed by the carboxyl groups of Lys and Arg. 2006 Thomson Learning, Inc.
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23 Classification of Enzymes
Enzymes are commonly named after the reaction
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23 Classification of Enzymes
1. Oxidoreductase: O
CH3 -C- COO Pyruvate
COOCH2 CH- NH3 + COO+
-
+ NADH + H
lactate dehydrogenase
2. Transferase:
COOAspartate amino C= O transferase CH2 CH2 COOAspartate -Ketoglutarate Oxalosuccinate COOCH2 C= O COO+
3. Hydrolase:
O CH3 -C- OCH 2 CH 2 N( CH3 ) 2 + H O Acetylcholinesterease 2 Acetylcholine
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23 Classification of Enzymes
4. Lyase:
COOCH2 C-COO - + H O 2 CH COOcis- Aconitate Aconitase COOCH2 C-COO HO C-H COOIsocitrate
5. Isomerase:
CH2 OPO 3 2 Phosphohexose O isomerase OH OH HO OH - D- Glucose-6-phosphate CH2 OPO 3 2 O H HO H H HO CH2 OH OH
- D-Fructose-6-phosphate
Tyrosine-tRNA synthetase
6. Ligase:
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L-tyrosyl-tDNA + AMP + PP
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23 Enzyme Activity
Enzyme activity: a measure of how much a
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23 Enzyme Activity
Figure 23.3 The effect of enzyme concentration on the rate
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23 Enzyme Activity
Figure 23.4 The effect of substrate concentration on the
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23 Enzyme Activity
Figure 23.5 The effect of temperature on the rate of an
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23 Enzyme Activity
Figure 23.6 The effect of pH on the rate of an enzyme-
catalyzed reaction. Substrate and enzyme concentrations and temperature are constant.
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23 Mechanism of Action
Lock-and-key model of enzyme mechanism. The enzyme is a rigid three-dimensional body. The enzyme surface contains the active site.
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23 Mechanism of Action
Induced-fit model The active site becomes modified to accommodate the substrate.
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23 Mechanism of Action
Figure 23.9 The mechanism of competitive inhibition. the inhibitor fits into the active site, thereby preventing the substrate from entering.
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23 Mechanism of Action
Figure 23.10 Mechanism of noncompetitive inhibition.
the inhibitor binds to a site other than the active site, thereby changing the conformation of the active site.The substrate no longer fits.
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23 Mechanism of Action
Figure 23.11 Enzyme kinetics in the presence and
absence of inhibitors.
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23 Mechanism of Action
Both the lock-and-key model and the induced-fit model emphasize the shape of the active site. However, the chemistry of the active site is the most important. Just five amino acids participate in the active sites in more than 65% of the enzymes studies to date. These five are His > Cys > Asp > Arg > Glu. Four these amino acids have either acidic or basic side chains; the fifth has a sulfhydryl group (-SH).
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23 Catalytic Power
Enzymes provide an alternative pathway for
reaction, one with a significantly lower activation energy and, therefore, a faster rate.
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23 Enzyme Regulation
Feedback control: an enzyme-regulation process
where the product of a series of enzymecatalyzed reactions inhibits an earlier reaction in the sequence.
f eedback inhi biti on E2 E3 E1
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23 Enzyme Regulation
Proenzyme (zymogen): an inactive form of an
enzyme that must have part of its polypeptide chain hydrolyzed and removed before it becomes active.
An example is trypsin, a digestive enzyme. It is synthesized and stored as trypsinogen, which has no enzyme activity. It becomes active only after a six-amino acid fragment is hydrolyzed and removed from the N-terminal end of its chain. Removal of this small fragment changes in not only the primary structure but also the tertiary structure, allowing the molecule to achieve its active form. 2006 Thomson Learning, Inc.
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23 Enzyme Regulation
Allosterism: enzyme regulation based on an
event occurring at a place other than the active site but that creates a change in the active site.
An enzyme regulated by this mechanism is called an allosteric enzyme. Allosteric enzymes often have multiple polypeptide chains. Negative modulation: inhibition of an allosteric enzyme. Positive modulation: stimulation of an allosteric enzyme. Regulator: a substance that binds to an allosteric 2006 Thomson Learning, Inc. enzyme. All rights reserved
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23 Enzyme Regulation
Figure 23.15 Effects of binding activators and inhibitors to
allosteric enzymes.
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23 Enzyme Regulation
Protein modification: the process of affecting
AD P inactive PKP
k inase
Pi
H2 O
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23 Enzyme Regulation
Isoenzyme: an enzyme that occurs in multiple
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23 Enzymes in Medicine
Enzyme assays useful in medical diagnosis.
En zyme Alan ine amin otrans ferase (ALT) Acid phosp hatase Alk alin e phosp hatase (ALP) Amylase Body Flu id Serum Serum Serum Serum D iseas e Diagnosed Hepatitis Prostate cancer Liver or bone dis ease Pan creatic diseas e Heart attack or hep atitis Heart attack Heart attack Heart attack
As partate aminotransferase (AST) Serum, Cereb rosp in al fluid Lactate dehydrogenas e (LD H) Serum Creatin e phosph ok inase (CK) Serum Ph os phohexose isomeras e (PHI) Serum
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23 Enzymes
End Chapter 23
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