The document discusses enzymes and their properties. It begins by defining enzymes as biological catalysts and describes their characteristics, including that they are not used up in chemical reactions. It then covers enzyme structure and function, classification, regulation, and clinical significance. Key points include: enzymes have an active site that facilitates reactions; there are multiple levels of enzyme classification based on the type of reaction catalyzed; factors like temperature, pH, and inhibitors can impact enzyme activity; isozymes and zymogens are discussed. Measurement of plasma enzyme levels is also described as being diagnostically useful.

1. The Pharmacologic
Approach to Biological
Catalytic Systems
ENZYMES

2. Enzymes – biological catalysts
Catalysts – (specifically positive* catalysts) are
substances that increase the speed of a chemical
reaction
 Not permanently changed
 Don’t cause the reaction to occur
 Not used up in chemical reactions so they
can be used over and over again
Overview of Enzymes

3. Enzymes – are organic catalysts produced by
living organisms. The reactant in an enzyme-
catalyzed reaction is called the “substrate”.
Overview of Enzymes

4. The small portion of the molecule that is
responsible for the catalytic action of the enzyme
is the “active site”.
Overview of Enzymes

5. Enzymes are superior to other catalysts in several
ways:
1. They have a much greater catalytic power.
CO2 + H2O carbonic anhydrase H2CO3
Overview of Enzymes

6. 2. Enzymes are highly specific with varying degrees
of specifity.
Absolute specificity – they act on one substrate and
only on that substrate
Stereospecificity – such enzymes that can detect
the difference between optical isomers (mirror
images) and select only one of such isomers
Overview of Enzymes

7. Reaction specificity – enzymes that catalyze certain
types of reactions
Group specificity – enzymes that catalyzes a group
of substances that contain specific compounds.
Overview of Enzymes
3. The activity of enzymes is closely regulated,
whereas catalyst activity is difficult to control.

8. [Most] 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.
Enzyme Reaction

9. Major Factors affecting Enzymatic Reactions:
(1) Temperature
(2) pH
(3) Substrate Concentration
(4) Availability of Catalyzing Enzymes
Enzyme Reaction

10. 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”.
Enzyme Reaction

11. Enzyme Reaction
Role of pH
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.

12. Enzyme Reaction
Role of pH
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
contain buffers, the pH usually does not vary too far
from the optimum values.

13. Enzyme Reaction
Effect of Substrate Concentration
As with the all chemical reactions, the rate of
formation is increased with an increase in
concentration of reactants. With an increased
concentration of substrate, the speed of the
reaction will increase until all available enzymes
becomes saturated with substrate.

14. Enzyme Reaction
Impact of Enzyme Availability
With an increase in the amount of enzyme,
the rate of reaction will increase, assuming an
unlimited supply of substrate.

15. Activators and Inhibitors
Activators/ Inducers – inorganic or organic
substances that tend to increase the activity of an
enzyme.
Inhibitors – any substance that will make the
enzyme less active or render it totally inactive.

16. Activators and Inhibitors
Types of Enzyme Inhibitors:
Competitive/ Reversible inhibitors – bind reversibly
to the active site, blocking the access by the
substrate.
Noncompetitive inhibitors – bind to another site
(the allosteric site) on the enzyme to render it less
active or inactive.

17. Activators and Inhibitors
Types of Enzyme Inhibitors:
Irreversible inhibitors – form strong covalent bonds
with the enzymes, rendering it inactive. This effect
cannot be overcome by increasing the
concentration of the substrate.

18. Activators and Inhibitors
Poisons
Many enzymes inhibitor are poisonous
because of their effect on enzyme activity. Mercury
and Lead compounds are poisonous because they
react with sulfhydryl groups ( - SH) of enzymes and
change their 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.

19. Activators and Inhibitors
Drugs
While some enzyme inhibitors are poisonous,
others are beneficial to life. Penicillin acts as an
enzyme inhibitor for transpeptidase, the very
enzyme that bacteria require to build their cell
walls. If the cell wall is lacking, osmotic pressure
causes the bacterial cell to burst and die.

20. Activators and Inhibitors
Drugs
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.

21. Mode of Enzyme Activity

22. Mode of Enzyme Activity

23. Lock-and-Key Model
Wherein the substrate must “fit” into the
active site of the enzyme – hence the specificity 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.
Mode of Enzyme Activity

24. Some 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) is called “coenzyme”.
Sometimes, enzymes require a metal ion activator
to function called a “prosthetic group”.
The Holoenzyme

25. 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 = holoenzyme
Coenzyme A is essential in the metabolism of
carbohydrates, lipids, and proteins in the body.
The Holoenzyme
active (whole enzyme)inactive

26. Enzyme Nomenclature
Formerly enzymes 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 and [more importantly]
the type of reaction involved, with the ending “-
ase”.

27. Enzyme Nomenclature
E N Z Y M E SUBTRATE or REACTION TYPE
Maltase Maltose
Urease Urea
Proteases Proteins
Carbohydrases Carbohydrates
Lipases Lipids
Hydrolases Hydrolysis Reaction
Deaminases Removing amines
Dehydrogenases Removing hydrogens

28. Enzyme Nomenclature
The Enzyme Commission number (EC
number) is a numerical classification scheme for
enzymes, based on the chemical reactions they
catalyze.
As a system of enzyme nomenclature, every
EC number is associated with a recommended
name for the respective enzyme.

29. Enzyme Nomenclature
Strictly speaking, EC numbers do not specify
enzymes, but enzyme-catalyzed reactions. If
different enzymes (for instance from different
organisms) catalyze the same reaction, then they
receive the same EC number.

30. Enzyme Nomenclature
Furthermore, through convergent evolution,
completely different protein folds can catalyze an
identical reaction and therefore would be assigned
an identical EC number (these are called non-
homologous isofunctional enzymes, or NISE).
By contrast, UniProt identifiers uniquely
specify a protein by its amino acid sequence.

31. Enzyme Classification
Top-Level Enzyme Commission Numbers
Group Reaction catalyzed Typical reaction Examples
EC 1
Oxidoreduct
ases
To catalyze oxidation/reduction reactions;
transfer of H and O atoms or electrons from
one substance to another
AH + B → A + BH
(reduced)
A + O → AO (oxidized)
Dehydrogenas
e, oxidase
EC 2
Transferase
s
Transfer of a functional group from one
substance to another. The group may be
methyl-, acyl-, amino- or phosphate group
AB + C → A + BC Transaminase,
kinase
EC 3
Hydrolases
Formation of two products from a substrate
by hydrolysis
AB + H2O → AOH + BH Lipase,
amylase,
peptidase

32. Enzyme Classification
Top-Level Enzyme Commission Numbers
Group Reaction catalyzed Typical reaction Examples
EC 4
Lyases
Non-hydrolytic addition or removal of
groups from substrates. C-C, C-N, C-O or
C-S bonds may be cleaved
RCOCOOH → RCOH +
CO2 or [X-A-B-Y] →
[A=B + X-Y]
Decarboxylase
EC 5
Isomerases
Intramolecule rearrangement, i.e.
isomerization changes within a single
molecule
ABC → BCA Isomerase,
mutase
EC 6
Ligases
Join together two molecules by synthesis of
new C-O, C-S, C-N or C-C bonds with
simultaneous breakdown of ATP
X + Y+ ATP → XY +
ADP + Pi
Synthetase

33. 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.
Enzyme Classification

34. Hydrolases – hydrolytic enzymes – catalyze the
hydrolysis of carbohydrates, esters and
proteins.
Lyases – are enzymes that catalyze the removal of
groups from substrates by means other than
hydrolysis, usually with the formation of
double bonds.
Enzyme Classification

35. 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.
Enzyme Classification

36. 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 ANG I converting enzyme angiotensin II
Angiotensin II increases the force of the
heartbeat and constricts the arterioles, thus causing
an increase in blood pressure.
Enzymes of the Kidney

37. Angiotensin II brings about the contraction of
the vascular smooth muscle and also triggers the
release of the hormone aldosterone which aids in
the retention of water. Actually, angiotensin II is the
most powerful vasoconstrictor known. It is an
octapeptide; Angiotensin I is a decapeptide.
Enzymes of the Kidney

38. 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.
Enzymes of the Kidney

39. 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 enzymatic reactions. Among the
chemotherapeutic agents are the antibiotics
and the antimetabolites.
Chemotherapy

40. Antibiotics – are compounds produced by one
microorganism that are toxic to another
microorganism. Among the most commonly
used are the penicillins and tetracyclines.
Chemotherapy

41. Penicillin
Tetracycline
Chemotherapy

42. Antimetabolites – are chemicals that have
structures closely related to those of the
substrate enzymes act on, thus inhibiting
enzyme activity. Mercaptopurine is used in
the treatment of leukemias. Some are
antibiotics.
Chemotherapy

43. 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.
Chemotherapy

44. The measurement of plasma enzyme levels
can be of great diagnostic value. Many other
plasma enzymes are useful in the diagnosis of
various diseases.
Clinical Significance of Plasma
Enzyme Concentrations

45. SERUM ENZYME MAJOR DIAGNOSTIC USE
Glutamate oxaloacetate transaminase
(SGOT)
Myocardial Infarction
Glutamate pyruvate transaminase (SGPT) Infectious Hepatitis
Trypsin Acute pancreatic disease
Ceruloplasmin Wilson’s Disease
Clinical Significance of Plasma
Enzyme Concentrations

46. SERUM ENZYME MAJOR DIAGNOSTIC 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 Hypertension
Clinical Significance of Plasma
Enzyme Concentrations

47. 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 forms and are of diagnostic value. LDH
has five forms.
Isozymes

48. 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
Clinical Significance of the
Relative Amount of LDH

49. 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 binders,
whereas those that decrease the protein's
activity are called noncompetitive inhibitors.
Allosteric Regulation

50. Allosteric regulation
This control of key enzymes is of utmost
importance to ensure that biologic processes
remain coordinated at all times to meet the
immediate metabolic needs of the cells.
Allosteric Regulation

51. Zymogens
are inactive precursors 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.
Zymogens

52. ZYMOGEN ACTIVE FORM OF ENZYME
pepsinogen pepsin
trypsinogen trypsin
prothrombin thrombin
Zymogens

53. Lactose Intolerance
Individuals who cannot eat food
containing lactose are said to be lactose intolerant.
They lack the enzyme lactase, which is required for
the hydrolysis of lactose.
As a result, lactose accumulates in the
intestinal tract and pulls water out of the tissues by
osmosis. This is turn causes abdominal cramps,
distention, and diarrhea.
Zymogens

54. Lactose Intolerance
To overcome such an effect today, an
individual may take Lactaid® orally to supply the
missing enzyme.
Zymogens

55. DAGHANG SALAMAT SA MGA
WALA NAMINAW…
GOD BLESS!
PADAYON sa gibati…