Enzymes used in the 3 sectors of medicine those are diagnostic, therapy and pharmaceuticals.

1. DAVANGERE UNIVERSITY
DEPARTMENT OF STUDIES IN BIOTECHNOLOGY
SEMINAR PRESENTATION ON
Enzymes in Medicines
Presented by
Reg no: 23PHDBIOTECH08
Research scholar
Department of studies in Biotechnology
Davangere University
Under the guidance of
Associate Professor
Department of studies in Biotechnology
Davangere University
2023

2. CONTENTS
1. Introduction
2. Enzymes in medicine
 Enzymes in diagnosis:
 Enzymes in treatment or therapy:
 Enzymes in pharmaceuticals:
3. Conclusion
4. References

3. Introduction:-
• Enzymes are proteins that act as catalysts which means they speed up chemical reactions,
they found everywhere from the bottom of the ocean to your backyard, and even inside our
own bodies.
• Enzymes are the crucial element of every living entity and also address the dominant
underlying causes of several health problems.
• Enzymes are preferred in medicine sector because of their substrate specificity and their
catalytic activity.
• Several drugs and pharmaceutical formulations are comprised of active pharmaceutical
ingredients (API) that are synthesized using the enzymes as important components of the
manufacture process.

4. Enzymes in medicine:-
In the field of medicine the enzymes are play a vital role in some abnormal conditions of human
beings.
Majorly 3 sectors of medicines having enzyme applications in vast, they are follows:
1. Enzymes in diagnostics.
2. Enzymes in treatment or therapy.
3. Enzymes in pharmaceuticals.
1. Enzymes in diagnostics:
The variety of enzymes are used for determination of various substances in the blood,
plasma/serum, and urine.
Example:-

5. 1. Biosensors for Blood Glucose:
• Glucose measurements are based on interactions with the enzyme glucose oxidase (GOD).
• GOD(β-D-glucose:oxygen 1-oxidoreductase) catalyzes the oxidation of β-D- glucose to
gluconic acid by utilizing molecular oxygen as an electron acceptor with simultaneous
production of hydrogen peroxide (Fig.1).
Figure.1: GOD reaction showing the oxidation of β-D-glucose to gluconic acid.

6. • Strip type biosensor for blood (GOD-HPR-dye), miniaturized thermal biosensor for whole
blood, Glucose sensor for whole blood, Glucose biosensor for serum from human blood etc.
• Amperometric biosensors, based on GOD, play a major role in blood sugar estimation.
Various GOD based biosensors are reported viz., Disposable strip- type biosensor for blood
and serum monitoring.
• glucose micro-biosensor are employed as detector in capillary electrophoresis (CE) for
determining the concentration of glucose in human serum.
2. Biosensors for Cholesterol:
• Cholesterol is an essential lipid biomolecule found in every cell membrane of all animal
and human cells. It is also considered as the precursor for other biomolecules, such as
steroids and hormones.
• The second-highest death-causing cardiac disease is atherosclerosis (thickening of arteries
due to the deposition of cholesterol in the inner walls of arteries), which is caused by
several factors. Thus, the estimation of the cholesterol level in blood is essential for the
valuation of atherosclerosis and other lipid-related diseases, and for the estimation of the
risk of myocardial infarction and thrombosis.

7. • Most of the developed biosensors use cholesterol oxidase (ChOx), which specifically
catalyzes the oxidation of cholesterol by molecular oxygen, and produces 4-cholesten-3-one
and hydrogen peroxide, and the produced hydrogen peroxide is determined electrochemically.

8. 3. Urea biosensors:
• Renal and liver disorders require a fast and accurate urea measurement in urine or blood
samples.
• Biosensors, based on urease have been used for urea determination.
• Urease catalyses the conversion of urea to hydrogenocarbonate and ammonium ion.
(NH2)2CO + 2H2O + H+ → 2NH4 + + HCO3 -
• the urea biosensor based on immobilization of urease into two oppositely charged clays,
which show a greater sensitivity.

9. 2. Enzymes in treatment or therapy:
The various enzymes are used as therapeutic agents in treating enzymes deficiencies
and other medical conditions in human being, this process referred as a new approach called
enzyme therapy.
In this regard enzyme therapy has numerous possible medical applications.
Examples:-
1. Adenosinedeaminase(ADA):-
• Is an enzyme involved in metabolism of purine bases.
• it is used for the treatment of Severe Combined Immunodeficiency Disease (SCID)
• It performs the breakdown of adenosine obtained through food and from the turnover of
nucleic acids in tissues. Its primary function in humans is the development and
maintenance of the immune system.
• It is the first successful use of an enzyme for the treatment of an inherited immunological
disorder. ADA plays an important role in the metabolism of excess adenosine present in the
circulation of SCID patients and decreases the toxicity to the immune system of the raised
adenosine levels.

10. • The success of the treatment depends upon the modification of ADA with PEG.
• PEG enhances the half-life of the enzyme (originally less than 30 Min) and reduces the
possibility of immunological reactions due to the bovine origin of the drug.
• The PEGylated forms of enzyme are commercially available as pegadamase bovine with
the brand name Adagen.
2. β-Glucocerebrosidase:
• β-glucocerebrosidase (d-glucosyl-N-acylsphingosinegluco hydrolase, EC 3.2.1.45) is an
enzyme with glucosylceramidase activity that hydrolyze the β-glucosidic linkage of the
chemical glucocerebroside, an intermediate in glycolipid metabolism.

11. • Mutations in the glucocerebrosidase gene cause Gaucher’s disease, a lysosomal storage
disease characterized by an accumulation of glucocerebrosides. Mutations in the
glucocerebrosidase gene are also associated with Parkinson’sdisease.
• This enzyme was approved for use in enzyme replacement therapy of Gaucher disease in
which an exogenous modified placental glucocerebrosidase was targeted to its correct
compartment within the body.
• The commercial formulations of the enzyme were available as alglucerase injection with
the brand name Ceredase.
3. Enzymes used as digestive aids:
• The α-galactosidase enzyme is taken as a digestive aid for people who develop the
symptoms of bloating, gas, and diarrhea upon ingesting foods like beans and Brassica
vegetables such as, cabbage, broccoli, Brussels, and so on.
• Lactose intolerance is a condition in which the patient is unable to produce sufficient
quantities of lactase enzyme that is responsible for the digestion of the milk sugar lactose.

12. • The lactose intolerant people cannot digest lactose containing foods and therefore, suffer
from stomach upset when they consume lactose containing food such as milk and milk
products containing lactose.
• Lactase supplements such as milk fortified with lactase, lactase powder are used to
overcome the lactose intolerance problems.

13. 4. Asperginase enzyme is used for the treatment of cancer or leukemia:
• A better enzyme therapy has been developed using PEGylated l-asparaginase with the name
Oncaspar (pegaspargase).
• It has shown better results for the treatment of acute lymphoblastic leukemia, acute myeloid
leukemia, and non-Hodgkin’s lymphoma.
• In other words, the normal cells, that is, the noncancerous cells can synthesize asparagine,
whereas the cancer cells cannot, and die in the presence of enzymes which degrade
asparagine.
• In fact, asparaginase and PEG-asparaginase are better alternatives to standard
Chemotherapy.

14. Case study
An Antioxidant Enzyme Therapeutic for COVID-19:
•Here in it is a therapeutic based on catalase, an antioxidant enzyme
that can effectively breakdown hydrogen peroxide and minimize the
downstream reactive oxygen species, which are excessively
produced resulting from the infection and inflammatory process, is
reported.
•Catalase assists to regulate production of cytokines, protect
oxidative injury, and repress replication of SARS-CoV-2, as
demonstrated in human leukocytes and alveolar epithelial cells, and
rhesus macaques, without noticeable toxicity.
•Such a therapeutic can be readily manufactured at low cost as a
potential treatment for COVID-19.
•this may provide an effective therapeutic solution for the pandemic,
as well as treatment of hyperinflammation in general.
https://doi.org/10.1002/adma.202004901.

15. 3. Enzymes in pharmaceuticals:
Immobilized enzymes are used in the manufacture of many drugs and antibiotics; this
is attainable as enzymes convert the pro–drug molecules to medication or beginning material to
medication.
Example:-
1. Synthesis of semisynthetic penicillins by penicillin acylases:
• Semisynthetic penicillins have been shown to have better properties than penicillin G and
V, such as higher stability, easier absorption and lesser side effects and are also better
candidates against the adaptive microbial resistance to antibiotics.
• Large-scale production of semisynthetic antibiotics that are derived from penicillin are
based on the condensation of the β-lactam nucleus with appropriate D-amino acid catalysed
by penicillin acylases.
• Penicillin G acylase has also been reported for enantioselective acylation of the L-
enantiomers of methyl esters of phenylglycine and 4 hydroxyphenylglycine in organic
solvents.

16. • The process resulted in easy isolation of the enantiomerically pure d-enantiomer, which is
of practical use in the preparation of β-lactam antibiotics.
Fig: Penicillin acylase catalyzed synthesis of some important semi-synthetic β-lactam antibiotics
2. Production of proteinogenic amino acids:
• The production of l-methionine, which is used in special diets, has been carried out using
enzymatic resolution with acylase of Aspergillus oryzae.
• Several hundred tons of l-methionine and l-valine are now produced each year using
enzyme membrane reactor technology to minimize the enzyme loss.

17. • Another amino acid that is preferably obtained through enzyme catalysis is l-aspartic acid.
The enzyme aspartase catalyzes the addition of amino group from ammonia to fumaric acid
to directly produce the l-aspartate, which is used on industrial scale to produce the artificial
sweetener L-aspartame.
• L-Alanine is produced from L-aspartate using aspartate β- decarboxylase enzyme.
3. Production of nonproteinogenic amino acids:
• Enzymatic production of d-amino acids and nonproteinogenic l-amino acids are becoming a
more acceptable and environmental-friendly method.
• D-Amino acids can be obtained as the by-products through enzymatic resolution of racemic
mixtures of DL-amino acids used to produce l-amino acids
• It is also possible to produce D-amino acids directly, the D-phenylglycine and p-hydroxy-
D-phenylglycine, which are produced usingthe enzyme system hydantoinase/carbamoylase.
• Dynamic kinetic resolution of N-succinyl amino acids carried out by two enzymes namely
the d-succinylase and N-succinyl amino acid racemase, which enantioselectively
hydrolyzed the N-succinyl-d-amino acids to their corresponding d-amino acids.

18. General uses of enzymes in pharmaceutics:
• Glucose isomerase enzyme is used in the fructose syrup manufacturing.
• Streptokinase enzyme is used in the production of drugs those are used for the blood clot
removal and heart attack treatment.
• Collagenase is used in medicines for the treatment of skin ulcer.
• Prolactazymes are administered to the patients suffer from the lactose intolerance.

19. Conclusion:-
 Enzymes that are used therapeutically have the great advantage of being economically
viable and reliable.
 Enzymes have become the major choice of medical diagnostics because of their high
specificity and catalytic activity.
 Biosensor technology could be envisioned and extended to the diagnosis of infectious
diseases.
 More research has to be focused on the diagnostic enzymes to research clinical
applications.

20. References:-
 Gautam kumar, Meghwanshi, Navpreet Kaur, Swati Verma, Narendra Kumar Dabi, Abhishek
Vashishtha, P. D. Charan, Praveen Purohit, H.S. Bhandari, N. Bhojak, Rajender Kumar
(2020), Enzymes for pharmaceutical and therapeutic applications. Biotechnology and Applied
Biochemistry, 14708744.
 Thiagarajan Hemalatha, Thiagamoorthy UmaMaheswari, Gunasekaran Krithiga, Palavesam
Sankaranarayanan& Rengarajulu Puvanakrishnan (2013), Enzymes in clinical medicine.
Indian journal of experimental biology Vol. 51. pp. 777-788.
 Ram Sarup Singh, Taranjeet Singh, Ashish Kumar Singh (2019), Enzymes as Diagnostic
Tools, Advances in Enzyme Technology, Elsevier B.V.