Enzymes are biological catalysts that speed up biochemical reactions without being consumed. They achieve this by lowering the activation energy of reactions. Hydrolases are a class of enzymes that catalyze hydrolytic reactions by adding water across bonds to break them down. One important hydrolase is human factor Xa, which promotes blood coagulation as part of the prothrombinase complex. Factor Xa can be inhibited by drugs like rivaroxaban, which selectively and directly inhibits both free and protein-bound factor Xa to interrupt the coagulation cascade and inhibit thrombin formation.

2. Introduction
2
● Enzyme, in Greek means in living (en= in, zyme = living).
● Biocatalysts or Organic catalysts, usually high molecular
weight proteins (exception-Ribozymes or RNAenzymes).
● Enzymes are chemical catalyst that control various
biochemical reactions without themselves being change.
● Most of enzymes produced by cell function within that cells
called as endozyme(intracellular).
● Some enzymes are liberated by cells and catalyse reactions
in cell enviornment called exozyme(extracellular).

3. Enzymes are Biological Catalysts
Enzymes are proteinsthat:
● Increase the rate of
reaction by lowering the
energy of activation.
● Catalyze nearly all the
chemical reactions taking
place in the cells of the
body.
● Have unique three-
dimensional shapes that fit
the shapes ofreactants.
3

4. Trivial Names of Enzymes
4
The name of anenzyme:
● Usually ends in –ase.
● Identifies the reacting substance.
For example,
sucrase catalyzes the reaction of sucrose.
● Describes the function of the enzyme.
For example
oxidases catalyze oxidation.
● Could be a common name, particularly for the
digestion enzymes such as pepsin and trypsin.

5. IUB Classification of Enzymes
● Enzymesareclassified according to the reaction
theycatalyze.
Class
● Oxidoreductases
● Transferases
● Hydrolases
● Lyases
5
● Isomerases
● Ligases
Reactions catalyzed
Oxidation-reduction
Transfer groups ofatoms
Hydrolysis
Add atoms/remove atoms
to/from a doublebond
Rearrange atoms
Use ATP tocombine
molecules

6. The Six Classes
●EC 1. Oxidoreductases
●EC 2. Transferases
●EC 3. Hydrolases
●EC 4. Lyases
●EC 5. Isomerases
●EC 6. Ligases

7. EC 1. Oxidoreductases
● Catalyze the transferof hydrogenoroxygenatoms or
electrons from one substrate toanother.
● Since these are ‘redox’ reactions, an electron
donor/acceptor is also required to complete the reaction.
AH2 +B → A+ BH2
Ex. Oxidases, Dehydrogenases, Reductases.
MAO, COX, HMGCOA reductase, DHFR.

8. EC 2. Transferases
 Catalyze group transfer reactions, excluding
oxidoreductases (which transfer hydrogenor
oxygenand are EC 1). Theseareof thegeneral
form:
A-X + B ↔ BX + A
 Ex: Transaminases (transfer aminogroup),
 Tyrosine Kinases (transfer Phosphategroup)

9. EC 3. Hydrolases
●Catalyze hydrolyticreactions.
●Bring hydrolysis of various compounds.
●A-X + H2O ↔ X-OH + A-H
●Ex: lipases, esterases, Amylases, peptidases/proteases,
etc.
Human factor xa, Bacterial serine protease,
ACE, Human carboxy peptidase,
AChE, Metalloprotease,
Phosphodiesterase 1 & 5

10. EC 4. Lyases
 Catalyze non-hydrolytic (covered in EC 3)removal of
functional groups from substrates, often creating a
double bond in the product; or the reverse reaction, ie,
addition of function groups across a double bond.
 Addition or removal of H2O, NH2, CO2.
A- X +B-Y → A=B + X-Y
Ex: Decarboxylases, Aldolases, Dehydrases,
Deaminases, Synthases, etc.
DOPA decarboxylase,
Carbonic anhydrase,
Histidine Caroxylase.

11. EC 5. Isomerases
● Catalyzes isomerization reactions, including epimerizations
andcis-trans
● isomerizations.
A →A’
Ex: Isomerases (Cis-Trans),Epimerases (D—L),
Phosphofrutokinase,
Thymidylate synthetase

12. EC 6. Ligases
● Catalyzes the synthesis of various (mostly C-X)
bonds, coupled with the breakdown of energy-
containing substrates, usually ATP.
A + B → A-B
ATP → ADP+iP
Ex: Synthetases, Carboxylases

13. Oxidoreductases
Class 1.Oxidoreductases-
•This class belong all enzymes of catalysing oxidation reduction
reactions.
•The substrate that is oxidized is regarded as hydrogen donor.
•Act on many chemical groupings to add or remove hydrogen
atoms
• The common name will be dehydrogenase, reductase can be
used.
• dehydrogenase in which removal of H from one substrate and
pass in to another substrate they not capable to passing H
directly to O2
• Oxidase is only used in cases where O2 is the acceptor.

14. MAO ( mono amino oxidase)
Location : In outer membrane of mitochondria and liver
Physiological role
• MAO catalyse the metabolism of catacholamine to their
inactive form aldehyde and further oxidation gives acids.
• Oxidative deamination
• detoxify foods

15. Types :
1)MAO- A
Location : Liver
Role: Predominate for metabolism of Nor epinephrine &
Dopamine.
2)MOA –B
Location : Liver
Role: Predominate for metabolism of serotonin.
INIBITORS or Antagonist:
IPRONIAZID
PHENELZINE
TRANYLCYPROAMINE
PARGYLINE
NIALAMIDE
ISOCARBOXAZID
• they are used in panic and hypersomnia condition
• they are used as antidepressant agent

16. PHENELZINE
ROLE : ANTIDEPRESSENT
Mechanism Of Action :
• Irreversible inibition
• It irreversibily inactivate the enzyme and break into
phenylethyl free radical, and nitrogen.
• That free radical inactivate the enzyme.
NH
NH2
NH
NH2
MAO
CH2
+ N2

17. TRANYLCYPROAMINE
MECHANISM OF ACTION
It Is Metobilised by MAO and Loose Electron To Flavin and
causes breaking of Carbon –Carbon Bond of cyclopropane ring
produce imine molecule and forms free radical With
COVALENT bond with enzyme that inhibits or inactive
MAO enzyme.
NH2
NH2
CH2
NH
MAO

18. CYCLOOXYGENASE (COX)
It is precursor of Prostaglandin E,D,F2,Prostacyclin and
Thromboxane.
Biological role
1) Play important Role in Prostaglandin formation which
causes pain, fever & inflammation
2) They sensitize a pain receptor
3) Prostaglandin cause vasodilation, cellular infiltration, and
sensitizes pain receptor.
4) They perform peroxidation reactions.
5) It perform two types of catalyst reaction
1) incorporation of oxygen in dioxygenase step to form PGG2.
2) PEROXIDATION to PGH2

20. CYCLOOXYGENASE
CYCLOGENASE TYPES
1)Cox-1 - Gastric cytoprotective
2)Cox -2 – Involved in normal renal development.
ROLE OF INIBITORS
COX -1 = Inibitors used as antiinflammatory, antipyretic,
analgesic and anticoagulant agent
Cox-2 = used as anti-neoplastic.
Examples of COX Inhibitors
COX -1 & COX -2 – Nimesulide, Paracetamol, Ibuprofen.
Selective COX -2 – Celecoxib, rafecoxib.

21. CYCLOOXYGENASE INHIBITORS
Drugs acting as inhibitors
• Inhibitors of COX 1 & COX2 used in different disease condition.
1)Reversible competitive inhibitor
Ibuprofen has similar binding like arachchidonic acid
2) Reversible non-competative inhibitor
Paracetomol activity is blocked by addition of antioxidant
3) Irreversible competative inhibitor
Aspirin – causes trans acetylation of enzyme COX.
Common MOA:
•COX Inhibitors inhibit COX -1 & COX -2 Which inhibit production of
PG and Thrmboxane A2 and hence inflammation is suppress.

22. HMG-CoA Reductase
3-hydroxy-3-methyl-glutaryl-coenzyme A reductase,
officially abbreviated (HMGCR)
Location: Hepatocytes
Role
• It is used in synthesis of cholesterol by conversion of HMG-
COA to mevalonate.
•Cholesterol play important role in body that is
- synthesis of hormone,
- in digestion, and as a building block.
• Two types of cholesterol HDL & LDL.
• Excessive deposition of LDL causes hyperlipidemia.
(Atherosclerosis)

23. Statins

24. The drugs which inhibit HMG CoAreductase enzyme includes :
Types of inhibitors.
1)Type-I statin-
Lovastatin, simvastatin, pravastatin
• This represent first generation statin and are derived from
Fungal metabolite and mainly contain polar head and
hydrophobic moiety.
• This effectively block active site of enzyme and lower cholesterol
level
• They are not easy to synthesize due to large asymmetric centers.
2) Type-II statin-
Fluvastatin, Atrovastatin
This represent second generation statin and are derived from
Fungal metabolite and mainly contain polar head and larger
hydrophobic moiety and easy to synthesize.
Side effects : liver toxicity , muscletoxicity

25. HMG-CoA Reductase
• Mechanism of action
• They are competitive inhibitors and compete with
natural substrate to bind with active site.
• They bind strongly as compared to natural
substrate.
• They contain hydrophobic moiety which binds
more strongly to active site
• It has structural similarity with mevaldyl CoA and
block formation of cholesterol.

26. DHFR (HUMAN)
Human DHFR is 186 amino acids protein with
molecular weight around 20 kDa
 It is useful in DNA synthesis and cell division by
maintaining a level of enzyme cofactor tetra hydrate
folate.
 cofactor tetrahydrate folate is useful in synthesis of
DNA and RNA.
Role
• DHFR has important role to regenerate folic acid in to its
reduced form tetrahydrofolate.

27. DNA, RNA/ Nucleic acid
HUMAN
Folic Acid
DHFR
METHOTREXATE
BACTERIA
CELL GROWTH

28. DHFR (HUMAN) inhibitors
• Example:
• Methotrexate:
• Act as a anticancer agents.
• Mechanism of action
METHOTREXATE
DHFR
FOLIC ACID-----------------FH4---- -------- DNA SYNTHESIS

29. DHFR(BACTERIAL)
 It is useful in DNA synthesis and provide one carbon moiety
for synthesis of pyrimidine nucleic acid base used for DNA
synthesis.
 If DNA synthesis is blocked then bacteria no longer grow and
divide .

30. DHFR (Bacterial) inhibitors
1. Inhibitors - Sulphonamide, sulphathiazole,
sulpadiazene, sulphapyridine . Etc
Mechanism:
It acts as competitive enzyme inhibition of
dihydropteroate synthetase and block DNA synthesis .
2. Trimethoprime
Mechanism
Trimethoprim is an inhibitor of DHFR of micro-
organisms, but resistance to its action develops quickly
when it is used alone, so it is usually combined with
another antibiotics.

31. Class 2. Transferases-
• Transfer chemical groups from one molecule to
another or to another part of the same molecule.
• AX +B ------- A + BX
-------
These enzyme are classified on basis of functional
group
1) NH2 (Transamination)
2) Ph (Transphosphorylation)
• Kinases are specialized transferases that regulate
metabolism by transferring phosphate from ATP to
other molecules.

32. Tyrosine Kinase (Leishmanial, Bacterial and Human)
 A tyrosine kinase is an enzyme that can transfer a phosphate
group from ATP to a protein in a cell.
 Itfunctions as an "on" or "off" switch in many cellular
functions.
 Tyrosine kinases are a subclass of protein kinase.
 The phosphate group is attached to the amino acid tyrosine on
the protein.
 Tyrosine kinases are a subgroup of the larger class of protein
kinases that attach phosphate groups to other amino acids
(serine and threonine).
 Phosphorylation of proteins by kinases is an important
mechanism in communicating signals within a cell (signal
transduction) and regulating cellular activity, such as cell
division.
 Protein kinases as drug targets in bacteria and Leishmania

34. Tyrosine kinase human
• Tyrosine kinase mainly helps in cell cycle progression.
• Tyrosine kinase helps in transmitting mitogenic signals .
• Tyrosine kinase is useful in regulating cell processes.
• Tyrosine kinase(protein) transforms normal cell into
neoplastic cell .
• Tyrosine kinase is regulate by following mechanism
1) protein- protein interaction
2) phosphorylation
3) Intercellular sequestration (binding of Iron ion with cell)
4) Proteolytic degradation of kinases

35. Bacterial tyrosine kinase
Protein Tyrosine kinase also found in bacteria
and classified as kinase .
They are involved in several biological function
1. Protein biosynthesis
2. Antibiotic resistance
3. Virulence mechanism(harmfulness of disease)
4. Polysaccharide synthesis

36. 1. Tyrosine Kinase Inhibitors
eg: Imatinib, Dasatinib, and Nilotinib.
2. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
eg: Gefitinib, Lapatinib.
3. Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors
eg. Semaxinib, Vatalanib, Sunitinib, Sorafenib.
Tyrosine kinase inhibitors
1 . Lapatinib
it is used as non- selective kinase inhibitor.
It is an orally active chemotherapeutic agent
it is used in solid cancers
it is also in breast cancer therapy

37. Tyrosine kinase inhibitors
3. Gefitnib
it inhibit tyrosine kinase domain of epidermal growth factor
receptor . Therefore, it is only effective in cancers with mutated and
overactive EGFR.
it is used in pancreatic, Breast, Lung cancer.
4. Erlotinib
it is used as non- selective tyrosine protein kinase inhibitor of
epidermal growth factor receptor.
Mechanism of action :
Inhibitors act as segment of the kinase domain that fixes the
enzyme in a closed or nonfunctional state, in which the protein
is unable to bind its substrate/phosphate donor, ATP.

38. Class 3. Hydrolases-
• Add water across a bond, hydrolyzing it
A-B + H₂O --------) AOH + BH
• These enzymes catalyze the hydrolytic cleavage of C-O,
C-N, C-C and some other bonds, which divide large
molecule in small.
• Carried out important degradative reactions in the body
during digestion like protease convert protein to amino
acids.
• Examples of common hydrolases are Esterase, Protease,
lipase, Glycosidase.
• These enzymes are usually names of substrate followed
by ‘ase’ e.g penicillinase , urease etc.

39. Human factor Xa
• An important type of hydrolase enzyme which favor
blood coagulation.
• Factor Xa generated from factor X by the action of
Ca++ and phospholipids the form Xa then combine
with Va to form prothrombinase complex which
transform prothrombin to thrombin.
• It is produce by activation of zymogens by intrinsic
or extrinsic factor.
• It is component of prothrombinase complex which
transform prothrombin to thrombin.

40. Combine with Va

41. Inhibitor
• Rivaroxaban
it is synthetic inhibitor of factor Xa of anticoagulant class and act directly on factor Xa
in coagulation cascade without using anti thrombin as mediator.
it is used in atrial fibrillation and appears effective in embolic strokes.
It causes bleeding in G.I

42. mechanism
• Rivaroxaban inhibits both free Factor Xa and Factor Va bound
in the prothrombinase complex
• It is a highly selective direct Factor Xa inhibitor with
oral bioavailability and rapid onset of action.
• Inhibition of Factor Xa interrupts the intrinsic and extrinsic
pathway of the blood coagulation cascade, inhibiting
both thrombin formation and development of thrombi.
• It allows predictable anticoagulation and dose adjustments
and routine coagulation monitoring as well as dietary
restrictions are not needed.

43. Bacterial serine protease
Location : animals ,plants , archaea , and viruses.
• Protease mainly performs proteolysis and causes catabolism by
hydrolysis of peptide bond that linked amino acid together in
polypeptide chain.

44. • A protease (also called peptidase or proteinase)
is any enzyme that:
• performs proteolysis; protein catabolism by hydr
olysis of peptide bonds.
• Proteases have evolved multiple times, and
different classes of protease can perform the
same reaction by completely different catalytic
mechanisms.

45. mechanism : A comparison of the two mechanisms used for proteolysis. enzyme is shown in black,
substrate protein in red and water in blue. The top panel shows 1-step hydrolysis where the enzyme
uses an acid to polarise water which then hydrolyses the substrate. The bottom panel shows 2-step
hydrolysis where a residue within the enzyme is activated to act as a nucleophile (Nu) and attack the
substrate. This forms an intermediate where the enzyme is covalently linked to the N-terminal half of
the substrate. In a second step, water is activated to hydrolyse this intermediate and complete catalysis.

46. classification
• Serine proteases : using serine alcohol
• Cysteine proteases : using cystine thoil
• Aspartate proteases : using aspartate carboxylic acid
• Threonine proteases : using threonine secondary
alcohol
• Glutamic acid proteases :using Glutamic carboxylic
acid
• Metallo proteases : using metal ,zinc
• Asparagine peptide lyases :involve asparagine.

47. inhibitors
• E-64
The compound was first isolated and identified from Aspergillus
japonicus in 1978
Mechanism :
It is an epoxide which irreversibly inhibit cystine peptidases.
it inhibit cystine peptidases such as papain , calpin , catespin ,
staphopain .
Used : anticancer agent as Bladder carcinoma .

48. Metalloproteases
• This are enzymes comprising of metal ion at
their active site and causing protein
degradation by hydrolysis of peptide bond.
• The enzymes uses following metal ion at
active site : Zn , Mn, CO etc.

49. Metalloprotease inhibitors
• Metalloprotease inhibitors are cellular inhibitors of the
Matrix metalloproteinases (MMPs).
• MMPs belong to a family of zinc-dependent neutral
endopeptidases.
• These enzymes have the ability to break down connective
tissue.
• The expression of MMPs is increased in various
pathological conditions like inflammatory conditions,
metabolic bone disease, to cancer invasion, metastasis
and angiogenesis.
• Examples of diseases are, hepatitis, glomerulonephritis,
atherosclerosis, asthma, autoimmune disorders of skin

50. inhibitors
• Marimastat
• used in the treatment of cancer,
• Marmiastat is an angiogenesis and metastasis inhibitor.
• As an angiogenesis inhibitor it limits the growth and
production of blood vessels.
• As an antimetatstatic agent it prevents malignant cells.
• it is an antineoplastic drug and it act as broad spectrum
metalloproteinase inhibitor

51. mechanism
• Marimastat is a broad spectrum matrix
metalloprotease inhibitor.
• It mimics the peptide structure of natural MMP
substrates and binds to matrix metalloproteases,
thereby preventing the degradation of the basement
membrane by these proteases.
• This antiprotease action prevents the migration of
endothelial cells needed to form new blood vessels.
• Inhibition of MMPs also prevents the entry and exit
of tumor cells into existing blood cells, thereby
preventing metastasis

52. • Batimastat
It is anticancer drug belonging to class
angiogenisis inhibitor .
It acts as metalloproteinase inhibitor by
mimicking natural peptides like MMP.

53. MECHANISM
• Angiogenesis inhibitors are unique cancer-
fighting agents because they tend to inhibit
the growth of blood vessels rather than tumor
cells.
• Angiogenesis inhibitor therapy does not
necessarily kill tumors but instead may
prevent tumors from growing. Therefore, this
type of therapy may need to be administered
over a long period

54. Angiotensinogen converting Enzyme
(ACE)
 ACE is membrane bound enzyme and also
metalloproteinase enzyme.
Causes hydrolysis of dipeptide fragment from
end decapeptide called Angiotensin I to give
octapeptide Angiotensin II .
 Angiotensin II causes constriction of blood
vessels and hence rise in Blood pressure.
 It stimulate thrist, Aldosterone secretion, ADH
stimulation, increases Na+/H+ exchanger
activity.

56. ACE INHIBITORS
ACE inhibitors causes inhibition of production
of angiotensin II.
Eg: Captopril, enalapril, lisinopril, Perindopril,
fosinopril, ramipril , imidapril, Benazepril etc.
Captopril
MECHANISM OF ACTION
• It inhibit ACE
• It has vasodilatation and inhibition of some renal function activities.
• It has shown mood elevating properties in some patient.
• Uses- In treatment of hypertension and CHF

57. LISINOPRIL
• Lisinopril is an ACE Inhibitor, meaning it blocks the actions of
angiotensin converting enzyme (ACE) in the renin-angiotensin-
aldosterone system (RAAS).
• keeping Angiotensin I from being converted to Angiotensin II.
The inhibition of this system causes an overall decrease in blood
pressure.

58. CARBOXYPEPTIDASES
• It is an polypeptidases obtained by breakdown of
proteins like trypsin , chymotrypsin etc.
• It mainly contain groups like –SH , Mg , Zn.
• carboxypeptidase is a protease enzyme that
hydrolyzes (cleaves) a peptide bond at the carboxyl-
terminal (C-terminal) end of a protein or peptide.
(Contrast with an aminopeptidase, which cleaves
peptide bonds at the other end of the protein.)
• Humans, animals, and plants contain several types
of carboxypeptidases that have diverse functions
ranging from catabolism to protein maturation.

59. • Classification
• A) on basis of active site
1)Enzymes that use a metal in the active site are
called "metallo-carboxypeptidases
2) carboxypeptidases that use active site serine
residues are called "serine carboxypeptidases
3) Those that use an active site cysteine are called
"cysteine carboxypeptidase

60. B) On basis of preference to substrate
1) Carboxypeptidases that have a stronger preference
for those amino acids containing aromatic or
branched hydrocarbon chains are called
carboxypeptidase A (A for aromatic/aliphatic)
2) Carboxypeptidases that cleave positively charged
amino acids (arginine, lysine) are called
carboxypeptidase B (B for basic).
3) A metallo-carboxypeptidase that cleaves a C-terminal
glutamate from the peptide N-acetyl-L-aspartyl-L-
glutamate is called "glutamate carboxypeptidase

61. Phisological role
• In digestion of food.
• In catabolism
• Help in mature proteins or regulate biological process.
• In biosynthesis of neuroendocrine peptides such as
insulin required carboxypeptidase.
• Also function in blood clotting,growth factor
production and wound healing.

62. Mechanism
• An enzyme which hydrolyses (cleaves) the peptide
bond of the COOH terminal amino acid from a
peptide;
• carboxypeptidase A removes aromatic or branched
hydrocarbons,
• while carboxypeptidase B removes positively
charged terminal lysine or arginine amino acid
residues

63. Inhibitors
• In molecular biology, the carboxypeptidase A inhibitor family is a family of
proteins which is represented by the well-characterised
metallocarboxypeptidase
• A inhibitor (MCPI) from potatoes.
• It is a mixture of approximately equal amounts of two polypeptide chains
containing 38 or 39 amino acid residues. The chains differ in their amino
terminal sequence only and are resistant to fragmentation by proteases.
• The potato inhibitor is synthesized as a precursor, having a 29 amino acid
N-terminal signal peptide, a 27 amino acid pro-peptide, the 39 amino acid
mature inhibitor region and a 7 amino acid C-terminal extension.
• The 7 amino acid C-terminal extension is involved in inhibitor inactivation
and may be required for targeting to the vacuole where the mature active
inhibitor accumulates.
•The N-terminal region and the mature inhibitor are weakly related to other
solananaceous proteins found in this family, from potato, tomato and
henbane, which have been incorrectly described
as metallocarboxypeptidase inhibitors

64. Class 4. Lyases
• In biochemistry, a lyase is an enzyme that catalyzes the breaking
(an "elimination" reaction) of various chemical bonds by means
other than hydrolysis (a "substitution" reaction) and oxidation, often
forming a new double bond or a new ring structure.
• The reverse reaction is also possible (called a "Michael addition").
For example, an enzyme that catalyzed this reaction would be a
lyase:
ATP → cAMP + PPiLyases
• Differ from other enzymes in that they require only
one substrate for the reaction in one direction, but two substrates
for the reverse reaction.
• Remove a group from or add a group to double bonds.
• Add water, ammonia or carbon dioxide across double bonds, or
remove these elements to produce double bonds
• In the common names, expressions like decarboxylase, aldolase,
dehydratase (in case of elimination of CO22, aldehyde, or water) are
used

65. • The lyases catalyzes the removal of small
molecule from larger substrate molecule.
• The lyases shows reversible reaction and
catalyzes the addition of smaller molecule to
larger substrate.
• They are classified on basis linkage they attack
like c-c ,c-o , c-n , c-s , c-x

66. DOPA decarboxylase
• It catalyzes several different decarboxylation reactions
such as
• 1. L DOPA to dopamine
• 2. 5-HTP to serotonin
• 3. L-Histidine to Histamine
• 4. Tryptophan to tryptamine
Role: play a important role in the synthesis of epinephrine
(Neurotransmitter).
Dopamine is catecholamine, plays an important role in
the human brain body that it reward motivated behavior.
Parkinsons diseases is caused by loss of dopamine
secreting area in brain.

68. DOPA Carboxylase inhibitors
• Used in treatment of several nervous system
diseases like Parkinson's diseases.
• Eg. Carbidopa.
• Is the drug used given to patient with Parkinson's
disease.
• It inhibit the peripheral metabolism of levodopa.
• That is allows a greater portion of peripheral
levodopa to cross BBB for central nervous system
effect.

69. Carbonic Anhydrase
• Carbonic Anhydrase is a zinc protein complex.
• Location in RBCs also small amount in muscle tissues, pancreases
and never found in plasma.
• The enzyme also found in some more amount in parietal cells of
stomach where it is involved in secretion of H+.
• H+ generated is exchanged for filtered Na+ in luminal fluid (Kidney)
• At the lung side the reaction in the RBCs start diffusion of O₂ from
alveolar air in to RBCs.
• The O₂ combine with Hb to form ( H.HbO₂) being strong acids and
ionizes in HbO₂¯ and H⁺.
• The H⁺ combine with HCO3¯ form H₂CO3 at site of tissues.
• The form carbonic acid which decomposes in the presence of CA to
form H₂O and CO₂.

71. Carbonic anhydrase inhibitor
• Carbonic anhydrase inhibitors are a class of
pharmaceuticals that suppress the activity of carbonic
anhydrase.
• Their clinical use has been established as
anti-glaucoma agents,
diuretics,
antiepileptics,
in the management of mountain sickness,
Gastric & duodenal ulcers,
hypertension,
neurological disorders,
osteoporosis.

72. 1. Acetazolamide,
• sold under the trade name Diamox among others, is a
medication used to treat glaucoma, epilepsy, Mountain
sickness, periodic paralysis, hypertension, and heart
failure.
• It may be used long term for the treatment of open
angle glaucoma and short term for acute angle closure
glaucoma.
2. Diuretics
• Dorzolamide
• Methazolamide
• Brinzolamide
• dichlorphenamide

73. 3. Brinzolamide
• (Tradenames Azopt, Alcon Laboratories, Befardin,
Fardi Medicals, is a carbonic anhydrase
inhibitor used to lower intraocular pressure in
patients with open-angle glaucoma or ocular
hypertension.
4. Topiramate
(brand name Topamax) is a broad-
spectrum anticonvulsant(antiepilepsy) drug

74. 5.Natural Inhibitors
Ellagitannins extracted from the pericarps of Punica
granatum, the pomegranate.
• such as punicalin, punicalagin, granatin
B,gallagyldilactone, casuarinin, pedunculagin and
tellimagrandin I, are carbonic anhydrase inhibitors.

75. Histidine decarboxylase
• Histidine decarboxylase is mainly involved in
production histamine from histidine with help of
vitamin B6.
Histidine decarboxylase
• Histidine ------------- histamine
Histidine decarboxylase
Vit B6
Vit B6

76. Physiological Role
• It dilates blood capillaries
• Lowers blood pressure
• It elevates secretion of gastric juice
• It elevates secretion of saliva
• It causes contraction of involuntary muscle
• It elevates tone of bronchiolar tissues
• It controls blood circulation in normal
organism

77. inhibitors
• Tritogualine
• Diphenhyramines
• Cyproheptadine
• Ranitidine
• Cimetidine
• MOA
This all are histidine decarboxylase inhibitors are used as antihistaminic
agents.
Role :
it is used in treatment of ulcer
It is used in treatment of allergic rhinitis
It is used to treat allergic reactions
Bronchial asthma
Anaphylactic shock
Blurring of vision
Hypotension

78. Esterase
• An esterase is hydrolase enzyme that splits ester into acid and
alcohol in chemical reaction with water called hydrolysis.
RCOOR’ H2O RCOOH + R’OH
• Classification
• Acetylesterase e.g cholinesterase
• Thiol esterase hydrolases e.g Thiol esterase
• Phosperic monoester hydrolase e.g alkaline phosphatase
• Sulfuric ester hydrolase
• Diphosperic monoester hydrolase
• Phosperic triester hydrolase
• Sulfuric ester hydrolases

79. Acetylcholine Esterase (AchE)
• Ach It is neurotransmitter for parasympathetic
nervous system stimulation of parsasympathetic
nervous system induces constriction of pupil and
bronchi
• Decrease in heart activity
• Increase in activity of digestive system i.e salivation.
• Motility of intestine is also increased.
• The free Ach present in blood and other tissue get
hydrolyzed by enzyme AchE present in serum.

81. AchE inhibitors
• Ach present in blood and tissue get hydrolyzed by Acetylcholine
Esterase into acetic acid and choline.
• Its inhibitors used in treatment of Treatment of myasthenia gravis
, Glaucoma, Alzheimer’s.
• MAO: it inhibit the AchE reversibly or irreversibly and increase
Ach level in blood.
• Examples
1. Reversible 2. Irreversible
• Physostigmine Organophosphrorous compounds and
• Neostigmine Carbamates.
• Rivastigmine
• Donezepil
• Galantamine
• Tacrine

82. • Physostigmine :
it is cholinesterase inhibitor used in treatment of Parkinson diseases
• Rivastigmine
it is cholinesterase inhibitor used in treatment of Parkinson diseases
• Donezepil
it is centrally acting reversible cholinesterase inhibitor used in treatment of Alzheimer
diseases
• Galantamine
it is an alkaloid obtained from flower of Galanthus caucasius. It is reversible
cholinesterase inhibitor
• Tacrine
it is centrally acting reversible cholinesterase inhibitor used in treatment of Alzheimer
diseases

83. Phospodiestarese
• This enzyme hydrolyzed cyclic phosphate ester of
AMP & GMP
• AMP & GMP are substrate of enzyme but shows
different active site.
Reaction
Cyclic Phosphate ester AMP & GMP.
PD

84. PDE1
• PDE1 (phosphodiesterase type 1)
• is a phosphodiesterase enzyme also known as calcium-
and calmodulin-dependent phosphodiesterase.
• It is one of the 11 families of phosphodiesterase
(PDE1-PDE11).
• PDE1 has three subtypes, PDE1A, PDE1B and
PDE1C which divide further into various isoforms.
• The various isoforms exhibit different affinities
for cAMP and cGMP

85. Physiological Role
• Intracellular second messengers such as cGMP and cAMP undergo
rapid changes in concentration in a response to a wide variety of
cell specific stimuli.
• The role of PDE1 enzymes is to degrade both cGMP and cAMP.
• Binding of PDE to cGMP and cAMP, respectively
• The various isoforms exhibit different affinities for cAMP and cGMP.
PDE1A and PDE1B preferentially hydrolyze cGMP,
• whereas PDE1C degrades both cAMP and cGMP with high affinity.
• For example, in airway smooth muscles of humans and other
species, generic PDE1 accounts for more than 50% of the hydrolytic
activity of cyclic nucleotides.
• It has been seen that PDE1 produces strong effects on agonist-
induced cAMP signaling but has little effect on the basal cAMP
level

86. PDE1 Inhibitors
• Many compounds reported as PDE1 inhibitors do not interact
directly with the catalytic site of PDE1 but interact during
activation, either at the level of calmodulin binding sites such
as compound KS505a or directly on Ca2+/calmodulin such
as bepril, flunarizine and amiodarone
• Initially PDE1 inhibitors were claimed to be effective vascular
relaxants. Also it is now known that such inhibitors are in fact
equally active against PDE5. Those inhibitors include
e.g. zaprinast.
• Nimodipine is a dihydropyridine that antagonizes/blocks
specifically L-type Ca2+-channel, and described as a PDE1
inhibitor.
• Vinpocetine was described as a specific inhibitor of basal and
calmodulin-activated PDE1. This effect leads to an increase of
cAMP over cGMP. It is also equally effective against PDE5.

87. PDE 5

88. PDE5 inhibitors
• Sildenafil, tadalfil,vardenafil are phospodiestarese 5
inhibitors used in treatment of erectile dysfunction
& maintaining desired lifestyle.
• Role
• Anti-inflammatory
• Vasodilator
• Smooth muscle relaxant.
• Antidepressant
• Antithrombotic
• Cardio tonic
• Improve cognitive function.

89. Isomerases
• Class 6. Isomerases-.
• These enzymes catalyze geometric or structural changes
within one molecule.
• According to the type of isomerism (interconvert
isomeric structures by molecular rearrangements)
• They may be called, cis-trans-isomerases, isomerases,
tautomerases, mutases and L to D isomerase,
• They are classified based on type of reaction
• 1) Racemases 2) Epimerases
• E.g alalnineracemase , Glucose phosphate isomrerases
etc

90. Thymidylate synthase (human & Fungal)
• This enzyme catalyze the methylation of deoxy
uridine monophosphate(dUMP) into deoxy
thymidine monophosphate (dTMP) using 5, 10,
methylene tetra phosphate as a coenzyme.
Thymidylate synthase
dUMP -------------------------- dTMP

91. Thymidylate synthetase in human & Fungi
• Thymidylate synthase is available from bacterial
version from “E-COLI “ by using recombinant
DNA technology .
• The bacterial enzyme is not identical to human
but are similar.

92. Thymidylate Synthase Inhibitors
• The inhibitors mainly block action of
Thymidylate synthase
• They mainly block synthesis of DNA .
• Types of inhibitors are
1) CB 3717
2) 5-Fluro uracil
3) Raltiterxed

93. CB 3717
• MECHANISM
the CB 3717 contains PTERIDINE RING which
mainly act as binding interaction to amino acid –
“ALA-263” , ” ARG-21” and also form hydrogen
bonding with water molecule and inhibit the
action of Thymidylate synthase .
It mainly act as anti-tumor agent.

94. 5-flourouracil
• It is Oncology Drug and used as colorectal cancer .
• It is analog of 5-fluorinated pyrimidine.
• Fluorouracil (5-FU), sold under the brand
name Adrucil among others, is a medication used
to treat cancer.

95. mechanism
• 5-FU acts in several ways, but principally as
a thymidylate synthase (TS) inhibitor.
• Interrupting the action of this enzyme blocks
synthesis of the pyrimidine thymidine, which is
a nucleoside required for DNA replication.

96. Raltitrexed
• Raltitrexed is chemically similar to folic acid and
is in the class of chemotherapy drugs which
inhibit enzymes: DHFR, thymidylate synthase.
• By inhibiting Thymidylate synthase (TS), thus
formation of precursor pyrimidine nucleotides,
raltitrexed prevents the formation of DNA and
RNA, which are required for the growth and
survival of both normal cells and cancer cells.

97. PHOSPOFRUCTOKINASE ( Leishmanial)
• Phospofructokinase is an kinase enzyme that
phosphorylate fructose 6 phosphate in glycolysis to
fructose 1,6, diphosphate .
• This enzyme catalyzed transfer of phosphoryl group
from ATP.
Fructose 6 Phosphate + ATP --- Fructose1, 6 diphosphate + ADP.
• PFKs It exist as Homotetramer in bacteria and
mammals and as octamer in yeast .
• PFKs Deficiency of it leads to glycogenesis type- VII (
Tarui’s disease) nausea, vomiting, muscle cramps
,myoglobunuria. etc

98. • Types of PFK
• 1) Phospofructokinase – 1 : 6 –Phospofructokinase , Phospohexakinase
• 2) Phospofructokinase -2 :Phospofructo kinase 2
• 3) 6 -Phospofructokinase -1 : It promote conversion of fructose 6
phosphate to fructose 1,6, diphosphate .
• 4) 6 -Phospofructokinase -2 :it is bifunctional enzyme that act as
both kinase and as phosphate by regulating synthesis of fructose
2,6 biphosphate and transformation to fructose 6 phosphate.
• Role of PFK
• It is important enzyme in all living life.
• It perform conversion of fructose 6- phosphate
to fructose 1,6-bisphosphate.

99. PFKs inhibitors
PFKs inhibitors is represented by sulforaphane an
isothyocynate derivatives are mainly found in cruciferous
vegetable, Such as broccoli.
Synthetic examples of inhibitors.
• Salicylic acid
• Acetyl salicylic acid
MECHANISM
This mainly inhibit PFK activity and glucose metabolism
and decrease cell viability ,and PKFS activity in breast
cancer .