Enzymes Biochemistry

1. ENZYMES
Muhammad Ramzan Ul Rehman 1

2. OVERVIEW of ENZYMES
Enzymes – are biologic catalysts.
Catalysts are substances that increase the
speed of a chemical reaction, it is not
permanently changed, nor does it cause the
reaction to occur, that is, a catalyst can increase
the speed of a reaction but cannot cause that
reaction if it would not occur in the absence of
catalyst. Since catalysts are not used up, they can
be used over and over again.
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3. OVERVIEW of ENZYMES
Enzymes – are organic catalyst produced by an
organisms. The reactant in an enzyme-catalyzed
reaction is called “substrate”.
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4. OVERVIEW of ENZYMES
The small portion of the molecule that is
responsible for the catalytic action of the enzyme
is the “active site”.
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5. OVERVIEW of ENZYMES
Enzymes are superior to other catalysts in several
ways:
1. They have a much greater catalytic power.
CO2 + H2O carbonic anhydrase H2CO3
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6. OVERVIEW of ENZYMES
2. Enzymes are highly specific with varying degrees
of specifity.
Absolute specifity – they act on one substrate and
only on that substrate.
Stereospecifity – such enzymes that can detect the
difference between optical isomers (mirror
images) and select only one of such isomers.
Reaction specifity – enzymes that catalyze certain
types of reactions.
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7. OVERVIEW of ENZYMES
Group specifity – enzymes that catalyzes a
group of substances that contain specific
compounds.
3. The activity of enzymes is closely regulated,
whereas the catalyst is difficult to control.
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8. ENZYME REACTION
Enzymes are proteins and therefore undergo all the
reactions that proteins do. That is, enzymes
can be coagulated by heat, alcohol, strong
acids, and alkaloidal reagents.
Temperature Requirement
The higher the temperature, the faster the
rate of reaction. The best temperature for enzyme
function – the temperature at which the rate of a
reaction involving an enzyme is the greatest – is
called the “optimum temperature”.
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9. Role of pH
ENZYME REACTION
Each enzyme has a pH range within which it
can best function. This is called “optimum pH
range” for that particular enzyme. For example, the
optimum pH range of pepsin, an enzyme found in
gastric juice, is approximately 2.0, whereas the
optimum pH range of trypsin, an enzyme found in
pancreatic juice, is near 8.2.
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10. ENZYME REACTION
If the pH of a substrate is too far from the
optimum pH required by the enzyme, that enzyme
cannot function at all. However, since body fluids
contains buffers, the pH usually does not vary too
far from the optimum values.
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11. ENZYME REACTION
Effect of Concentration
As with the all chemical reactions, the speed
is increased with an increase in concentration of
reacctants. With an increased concentration of
substrate, the rate of the reaction will increase until
available enzyme becomes saturated with
substrate.
Also with an increase in the amount of
enzyme, the rate of reaction will increase, assuming
an unlimited supply of substrate.
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12. ACTIVATORS and INHIBITORS
Activators – inorganic substances that tend to
increase the activity of enzyme.
Inhibitors – any substance that will make the
enzyme less active or render it inactive.
Competitive inhibitors – binds reversibly in
the active site and so block the access by the
substrate.
Incompetitive inhibitors – bind to another site
on the enzyme to render it less active or inactive.
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13. ACTIVATORS and INHIBITORS
Irreversible inhibitors – form strong covalent
bonds with the enzymes, rendering it inactive. This
effect can’t be overcome by increasing the
concentration of the substrate.
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14. Poisons
ACTIVATORS and INHIBITORS
Many enzymes inhibitors are poisonous
because their effect on enzyme activity. Mercury
and Lead compounds are poisonous because they
react with sulfhydryl groups ( - SH) of an enzymes
and so change its conformation. The subsequent
loss of enzyme activity leads to the various
symptoms of lead and mercury poisoning, such as
loss of equilibrium, hearing, sight, and touch, which
are generally irreversible.
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15. Drugs
ACTIVATORS and INHIBITORS
While some enzyme inhibitors are poisonous,
others are beneficial to life. Pencillin acts as an
enzyme inhibitor for transpeptide, a substance that
bacteria need to build their cell walls. If the cell wall
is lacking, osmotic pressure causes the bacterial cell
to burst and die. However, new strains of bacteria
have developed an enzyme, penicillinase, that
inactivates penicillin. To destroy these new strains,
synthetically modified penicillins have been
prepared so that this antibiotic remains effective.
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16. MODE OF ENZYME ACTIVITY
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17. MODE OF ENZYME ACTIVITY
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18. ACTIVATORS and INHIBITORS
Lock-and key Model
Wherein the substrate must “fit” into the
active site of the enzyme – hence the specifity of
the enzyme.
Induced-Fit Model
Suggests that the active site is not rigid as the
Lock-and-Key Model, but flexible. That is, the site
changes in conformation upon binding to a
substrate in order to yield an enzyme-substrate fit.
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19. APOENZYMES and COENZYMES
Other enzymes are conjugated proteins – they
contain a protein and non-protein part. Both parts
must be present before the enzyme can function.
The protein part is called the “apoenzyme”
and the non-protein (organic part) is called
“coenzyme”.
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20. Coenzymes
APOENZYMES and COENZYMES
are not proteins and so are not inactivated by
heat. Examples of coenzymes are the vitamins or
compounds derived from vitamins. The reaction
involving a coenzyme can be written as follows:
coenzyme + apoenzyme = enzyme
Coenzyme A is essential in the metabolism of
carbohydrates, lipids, and proteins in the body.
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21. NOMENCLATURE
Formerly enzyme were given names ending in
“-in”. With no relation being an indicator between
the enzyme and the substance it affects – the
substrate.
The current system for naming enzymes uses
the name of the substrate or the type of reaction
involved, with the ending “-ase”.
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22. NOMENCLATURE
ENZYME SUBTRATE or REACTION TYPE
Maltase Maltose
Urease Urea
Proteases Proteins
Carbohydrases Carbohydrates
Lipases Lipids
Hydrolases Hydrolysis Reaction
Deaminases Removing amines
Dehydrogenases Removing hydrogens
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23. CLASSIFICATION
Oxidoreductases – are enzymes that catalyze
oxidation-reduction reactions between two
substrates. The enzymes of the oxidation-reduction
reactions in the body are important
because these reactions are responsible for the
production of heat and energy.
Transferases – are enzymes that catalyze the
transfer of a functional group between two
substrates.
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24. Hydrolases – hydrolytic enzymes – catalyze the
hydrolysis of carbohydrates, esters and
proteins.
Lyases – are enzymes that catalyzes the removal of
groups from substrates by means other than
hydrolysis, usually with the formation of
double bonds.
CLASSIFICATION
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25. CLASSIFICATION
Isomerases – are enzymes that catalyze the
interconversion of cis-trans isomers.
Ligases – or synthetases, are enzymes that catalyze
the coupling of two compounds with breaking of
pyrophosphate bonds.
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26. ENZYMES of the KIDNEY
If an individual’s blood pressure drops, as in
the case of hemorrhaging or in hypokalemia, the
kidneys secrete the enzyme renin (sometimes
considered as a hormone) into the bloodstream.
angiotensinogen renin angiotensin I converting enzyme angiotensin II
Angiotensin II increases the force of the
heartbeat and constricts the arterioles, thus
causing an increase in blood pressure.
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27. ENZYMES of the KIDNEY
Angiotensin II brings about the contraction of
smooth muscle and also triggers the release of the
hormone aldosterone which aids in the retention of
water. Actually, angiotensin I is the most powerful
vasoconstrictor known. It is an octapeptide;
Angiotensin I is a decapeptide.
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28. ENZYMES of the KIDNEY
Other kidney enzymes include glucose-6-
phosphatase, which is involved in the removal of
the phosphate group from glucose-6-phosphate,
thereby enabling glucose to diffuse from the cell
into the blood stream;
Glutaminase, which is involved in the
conversion of glutamine into glutamic acid and
NH4+ ; and a
hydroxylase, which is involved in the
synthesis of calcitriol.
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29. CHEMOTHERAPY
Chemotherapy is the use of chemicals to destroy
infectious microorganisms and cancerous
cells without damaging the host’s cells. These
chemicals function by inhibiting certain cellular
enzyme reactions. Among the
chemotherapeutic agents are the antibiotics and
the antimetabolites.
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30. CHEMOTHERAPY
Antibiotics – are compounds produced by one
microorganisms that are toxic to another
microorganisms. Among the most commonly
used are the penicillin and tetracyclin.
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31. ENZYMES Elino, M.M.H.
CHEMOTHERAPY
Penicillin
Tetracycline
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32. CHEMOTHERAPY
Antimetabolites – are chemicals that have
structures closely related to those of the substrate
enzymes act on, thus inhibiting enzyme activity.
Mercaptopurine are used in the treatment
of leukemias. Some are antibiotics.
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33. CHEMOTHERAPY
One of the most promising new
chemotherapeutic agent in decades is taxol, a
natural product obtained from the bark of Pacific
yew trees. Taxol acts by interfering with cellular
growth and function and is very effective in
shrinking a variety of tumors, particularly in
advanced cases of ovarian and breast cancer.
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34. CLINICAL SIGNIFICANCE OF PLASMA ENZYME CONCENTRATIONS
The measurement of plasma enzyme levels can be
of great diagnostic value. Many other plasma
enzymes are useful in the diagnosis of various
diseases.
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35. CLINICAL SIGNIFICANCE OF PLASMA ENZYME CONCENTRATIONS
SERUM ENZYME MAJOR DIAGNOSTI C USE
Glutamic oxaloacetic transaminase
(SGOT)
Myocardial Infarction
Glutamic pyruvic transaminase
(SGPT)
Infectious Hepatitis
Trypsin Acute pancreatic disease
Ceruloplasmin Wilson’s Disease
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36. CLINICAL SIGNIFICANCE OF PLASMA ENZYME CONCENTRATIONS
SERUM ENZYME MAJOR DIAGNOSTI C USE
Amylase Liver and pancreatic disease
Acid phosphate Prostate Cancer
Alkaline phosphatase Liver or bone disease
Creatine phosphokinase Myocardial infarction, muscle
disorders
Lactate dehydrogenase Myocardial Infarction, leukemia,
anemia
Renin Muhammad Ramzan Ul Rehman Hypertension 36

37. ISOZYMES
Isozymes or Isoenzymes
are enzymes with the same function but
slightly different structural features. The reason for
their existence is not unknown, but they are made
use of clinically. Lactate dehydrogenase (LDH),
creatine kinase, and alkaline phosphatase all occur
in isoenzyme form and are diagnostic value. LDH
has five forms.
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38. CLINICAL SIGNIFICANCE OF RELATIVE AMOUNT OF LDH
Condition Isoenzyme Pattern
Myocardial Infarction
Moderate elevation of LDH1;
Slight elevation of LDH2
Acute Hepatitis
Large elevation of LDH5;
Moderate elevation of LDH4
Muscular Dystrophy Elevation of LDH1, LDH2, LDH3
Megaloblastic Anemia Large elevation of LDH1
Sickle-cell Anemia Moderate elevation of LDH1, LDH2
Arthritis with Joint effusions Elevation of LDH5
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39. ALLOSTERIC REGULATION
Allosteric regulation
is the regulation of an enzyme or
other protein by binding an effector molecule at
the enzyme's allosteric site (that is, a site other
than the active site).
Effectors that enhance the protein's
activity are referred to as allosteric enzymes,
whereas those that decrease the protein's
activity are called noncompetitive inhibitors.
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40. ALLOSTERIC REGULATION
Allosteric regulation
This control of key enzymes is utmost
importance to ensure that biologic processes
remain coordinated at all times to meet the
immediate metabolic needs of the cells.
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41. ZYMOGENS
Zymogens
are inactive pprecursors of enzymes.
Most digestive and blood-clotting enzymes exist in
the zymogen form, until activated.
In the case of digestive enzymes, this is
necessary to prevent digestion of pancreatic and
gastric tissue. For blood clotting, it is to avoid
premature of blood cells.
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42. ZYMOGENS
ZYMOGEN ACTIVE FORM OF ENZYME
pepsinogen pepsin
trypsinogen trypsin
prothrombin thrombin
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43. ZYMOGENS
Lactose Intolerance
Individuals who cannot eat food
containing lactose are said to be lactose intolerant.
They lack enzyme lactase, which is requires for the
hydrolysis of lactose.
As a result, lactose acuumulates in the
intestinal tract and pulls water out of the tissues by
osmosis. This is turn causes abdominal cramps,
distention, and diarrhea.
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44. ZYMOGENS
Lactose Intolerance
To overcome such an effect today, an
individual may take Lactaid orally to supply the
missing enzyme.
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45. GOD BLESS!
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