Transcript Chapter 20 Enzymes and Vitamins

Names of Enzymes
The name of an enzyme
•Usually ends in ase.
•Identifies the reacting substance. For example,
sucrase catalyzes the hydrolysis of sucrose.
• Describes the function of the enzyme. For
example, oxidases catalyze oxidation.
• Can be a common name, particularly for the
digestive enzymes, such as pepsin and trypsin.
Enzyme Classification
Enzymes are classified by the type of reaction they catalyze.
Oxidoreductases
Catalyze oxidation-reduction reactions
Transferases
Catalyze transfer of groups between compounds
alanine
transaminase
alanine
-ketoglutarate
O
NH2
CH3CCO2 + O2CCH2CH2CHCO2
pyruvate
glutamate
Enzyme Classification
Hydrolyases
Catalyze hydrolysis reactions
R
N CH
H
R
O
C
N CH
CO2 + H2O
peptidase
H
Lyases
Catalyze addition or removal of groups without
hydrolysis or oxidation
Enzyme Classification
Isomerases
Catalyze rearrangement reactions
triose phosphate
isomerase
glyceraldehyde-3-phosphate
dihydroxyacetone phosphate
Ligases
Catalyze reactions that connect molecules - requires energy input
O
CH3CCO2 + CO2 + ATP
pyruvate
pyruvate
carboxylase
O
O2C CH2CCO2 + ADP + Pi + H +
oxaloacetate
Enzyme Cofactors
• A simple enzyme is an active enzyme that
consists only of protein.
• Many enzymes are active only when they
combine with cofactors such as metal ions or
small molecules.
• A coenzyme is a cofactor that is a small
organic molecule such as a vitamin.
• A holoenzyme is the enzyme + cofactor, an
apoenzyme is the enzyme – cofactor.
Metal Ions as Cofactors
Many active enzymes
require a metal ion.
Zn2+, a cofactor for
carboxypeptidase,
stabilizes the carbonyl
oxygen during the
hydrolysis of a
peptide bond.
Water-Soluble Vitamins
Water-soluble vitamins are
• Soluble in aqueous solutions.
• Cofactors for many enzymes.
• Not stored in the body.
Thiamine (Vitamin B1)
Coenzyme form - thiamine pyrophosphate
Coenzyme for decarboxylation reactions
Nutritional sources: milk, grains, green vegetables
Deficiency disease: beriberi
Riboflavin (Vitamin B2)
Coenzyme form - FAD
Coenzyme for oxidation-reduction reactions
Nutritional sources: milk, grains, green vegetables
Deficiency symptoms: dermatitis, tongue
inflamation
Niacin (Vitamin B3)
Coenzyme forms - NAD+ and NADP+
Coenzyme for oxidation-reduction reactions
Nutritional sources: milk, grains, green vegetables
Deficiency disease: pellegra (rough skin)
Pantothenic Acid (Vitamin B5)
Coenzyme form - coenzyme A
Coenzyme for transfer of acyl groups
Nutritional sources: most foods
Deficiency symptoms: fatigue, apathy, muscle cramps
Pyridoxine (Vitamin B6)
Coenzyme form - pyridoxal pyrophosphate
Coenzyme for amino group transfer reactions
Nutritional sources: milk, grains, green vegetables
Deficiency symptom: dermatitis, anemia
Biotin (Vitamin B7)
Coenzyme form - biotin
Coenzyme for carboxylation reactions
Nutritional sources: milk, liver, also produced by
intestinal bacteria
Deficiency symptom: dermatitis
Folic Acid (Vitamin B9)
Coenzyme form - tetrahydrofolate
Coenzyme for intermolecular one-carbon transfers
Nutritional sources: green leafy vegetables, yeast,
and produced by intestinal bacteria
Deficiency symptoms: anemia, diarrhea
Vitamin B12
Coenzyme form - 5’deoxyadenosylcobalamin
Coenzyme for intramolecular rearrangements
Nutritional sources: milk, eggs, other animal products
Deficiency disease: pernicious anemia
Vitamin C
Coenzyme form - vitamin C
Coenzyme for hydroxylation reactions
Nutritional sources: citrus fruits, tomatoes, broccoli
Deficiency disease: scurvy (weakened collagen)
Zymogen
Inactive precursor form of an enzyme or other protein
Digestive enzymes
pepsinogen
trypsinogen
pepsin
trypsin
chymotrypsinogen
chymotrypsin
procarboxypeptidase
carboxypeptidase
Blood-clotting proteins
prothrombin
fibrinogen
Insulin
proinsulin
thrombin
fibrin
insulin
Active Site
The active site
• Is a region within an
enzyme that fits the
shape of the reacting
molecule called a
substrate.
• Contains amino acid
R groups that bind
the substrate.
• Releases products
when the reaction is
complete.
Enzyme Catalyzed Reaction: Basic Mechanism
The proper fit of a substrate (S) in an active site
forms an enzyme-substrate (ES) complex.
E+S
ES
Within the ES complex, the reaction occurs
to convert substrate to product (P).
ES
E+P
The products, which are no longer attracted to
the active site, are released.
Overall, substrate is converted to product.
E+S
ES
E+P
Enzyme Catalyzed Reaction
In an enzyme-catalyzed
reaction
• A substrate attaches to
the active site.
• An enzyme-substrate
(ES) complex forms.
• Reaction occurs and
products are released.
• An enzyme is used
over and over.
E+S
ES
E+ P
Enzymes are Biological Catalysts
Enzymes are proteins that
• Catalyze nearly all the chemical reactions taking
place in the cells of the body.
• Increase the rate of reaction by providing pathway
with a lower the energy of activation.
Lock and Key Model
In the lock-and-key model of enzyme action,
• The active site has a rigid shape.
• An enzyme only binds substrates that exactly fit
the active site.
• Only substrates with the matching shape can fit.
• The substrate is the key that fits that lock.
Induced-fit Model
In the induced-fit model of enzyme action,
• Enzyme structure is flexible, not rigid.
• Enzyme and substrate adjust the shape of the
active site to bind substrate.
• Shape changes improve catalysis during reaction.
• The range of substrate specificity increases.
Enzyme Specificity
Enzymes may recognize and catalyze
• A single substrate. (absolute specificity)
Example: urease
• A specific stereoisomer (stereochemical specificity)
Example: D-amino acid oxidase
• A group of similar substrates.(group specificity)
Example: alcohol dehydrogenase
• A particular type of bond.(linkage specificity)
Example: lipase
Substrate Concentration
An increase in substrate
concentration
• Increases the rate of
reaction (at constant
enzyme concentration).
• Eventually saturates
an enzyme with
substrate to give
maximum activity.
Enzyme Concentration
An increase in enzyme
concentration
• Increases the rate of
reaction (at constant
substrate concentration).
• Binds more substrate
with enzyme.
Temperature and Enzyme Action
Enzymes
• Are most active at an
optimum temperature
(usually 37°C in
humans).
• Show little activity at
low temperatures.
• Lose activity at high
temperatures as
denaturation occurs.
pH and Enzyme Action
Enzymes
• Are most active at
optimum pH.
• Contain R groups
of amino acids with
proper charges at
optimum pH.
• Lose activity in
low or high pH as
charges change.
Optimum pH Values
Enzymes in
• The body have an optimum pH of about 7.4.
• Certain organs, enzymes operate at lower and higher
optimum pH values.
Feedback Control (Feedback Inhibition)
In feedback control
• A product acts as a negative regulator.
• As the concentration of the end product increases,
the end product binds with the first enzyme (E1) in
a sequence decreasing the rate of the first reaction.
Specific Example of Feedback Inhibition
Biosynthesis of Threonine
Allosteric Enzymes
An allosteric enzyme is
• An enzyme in a reaction sequence that binds a
regulator substance.
• A positive regulator is one that enhances the
binding of substrate and accelerates the rate of
reaction.
• A negative regulator when it prevents the
binding of the substrate to the active site and
slows down the rate of reaction.
Irreversible Inhibition
In irreversible inhibition, a substance
• Bonds with R groups at the active site.
• Destroys enzyme activity.
Competitive Inhibition
A competitive inhibitor
• Has a structure that is
similar to that of the
substrate.
• Competes with the
substrate for the active
site.
• Has its effect reversed
by increasing substrate
concentration.
Malonate and Succinate Dehydrogenase
Malonate
• Is a competitive
inhibitor of
succinate
dehydrogenase.
• Has a structure
that is similar to
succinate.
• Inhibition is
reversed by adding
succinate.
Noncompetitive Inhibition
A noncompetitive inhibitor
• Binds to a site other than the
active site.
• Alters the arrangement of
groups in the active site.
• Doesn’t prevent binding of the
substrate, but blocks activity.
• Cannot have its effect reversed
by adding more substrate.
Some Medical Uses of Inhibitors
Cancer chemotherapy
Methotrexate (amethopterin) - inhibits synthesis of
thymine (part of DNA)
5-Fluorouracil - inhibits DNA synthesis
Antibiotics
Sulfa drugs - inhibits synthesis of folic acid
Tetracyclines - inhibit protein synthesis
Penicillin - inhibits bacterial cell wall synthesis
Neural Transmission using Acetylcholine
Release: inhibited by toxin from Clostridium botulinum
Binding: inhibited by curare
Breakdown: inhibition of acetylcholine esterase
Inhibitors: nerve gases (sarin, tabun),
insecticides (malathion, parathion)
Isoenzymes
Isoenzymes
• Catalyze the same reaction in different tissues
in the body.
• Such as lactate dehydrogenase (LDH), which
converts lactate to pyruvate, consists of five
isoenzymes.
• Can be used to identify the organ or tissue
involved in damage or disease.
• Such as LDH have one form more prevalent in
heart muscle and another form in skeletal
muscle and liver.
Isoenzymes of Lactate Dehydrogenase
Diagnostic Enzymes
Levels of enzymes
CK, LDH, and AST
• Are elevated
following a heart
attack.
• Are used to
determine the
severity of the
attack.
Diagnostic Enzymes
Diagnostic
enzymes
• Determine the
amount of
damage in
tissues.
• That are elevated
may indicate
damage or
disease in a
particular organ.
Enzyme Classification
isomerase
transferase
Enzyme Classification
oxidoreductase
lyase
Enzyme Classification
ligase
hydrolase