Joan Christie W.

(11320120002)
Ong. Nicky Alexander (11320120006)
Aristya Wismoyo (11320120017)
Danika Augusta S. (11320120019)
Overview : Enzyme
Are naturally occurring bio-catalysts found in the living organisms
Combine molecules to produce new products or break molecule into smaller parts
Require specific conditions for efficient functioning like optimal temperature, pH,
concentration.
Lower activation energy (amount of energy required for reaction to occur)
Without enzymes, reactions would not occur fast enough to sustain life
Will only bind with certain substrates. Active site is where chemical reaction
occurs


Overview : Sources of Enzymes
Enzymes can be attained from animals (chimosin, pepsin, trypsin), plants (ficin, papain,
bromelain), or microorganisms (pectinases, glucoamylase, alpha amylase).
The reason for a tendency to use microbial enzymes on industrial scale :
plentiful supplied and producer can control all phases of the enzyme production
commercial enzyme preparation is well standardized
can often produce several different enzymes producer can operate the fermentation plant to shift
the production to one enzyme in detriment of the others coping with the market fluctuations
presents high growing capability huge amounts of enzyme can be produced in a
short period of time
can be genetically manipulated DNA recombinant technique to improve its enzyme
production capability

Overview : Enzyme Production
Commercially valuable enzymes are usually produced through processes such as
extraction from adequate sources, filtration, centrifugation, precipitation, purification,
drying, stabilization, standardization, and packaging
In biotechnology, all unit operations comprised between filtration and packaging are
generally said downstream processing
Enzymes of animal and plant origin are produced through maceration of tissues,
organs, leaves, and fruits - followed by extraction with water or organic solvent
Differently, microbial enzymes are attained from either prokaryotic
(bacteria) or eukaryotic (yeasts, fungi, mainly) cells cultured in a
liquid or semi-solid medium, carried out in a special reactor called
fermenter, being the process known as fermentation
Enzymes and Health Care Industries
Health care (medical) industry as generally consisting of :
hospital activities
medical and dental practice activities
other human health activities such as acupuncture and music therapy
health care equipment and services; and
pharmaceuticals, biotechnology and related life sciences.
Development of medical applications for enzymes have been at least as extensive
as those for industrial applications, reflecting the magnitude of potential rewards.
Variety of enzymes and their potential therapeutic applications are
considerable
At present, the most successful applications are extracellular : purely
topical uses, removal toxic substances and treatment of life-threatening
disorders within the blood circulation.
Topical Medication Uses
Enzymes is used in skin care products and especially used for exfoliation and
anti-inflammation.
For exfoliation :
Certain enzymes are effective exfoliants and can be gentler than other methods like scrubs
and microdermabrasion.
The upper layer of your skin is mostly made of dead skin cells containing keratin protein.
The enzymes work by specifically breaking down the keratin protein, resulting in smoother skin.
Enzymes can also penetrate the skin to help cleanse pores and improve skin tone and texture.
Look for fruit enzymes like papain (papaya), pineapple or blueberry.
Medical Application of Enzymes
There are four different types of uses for enzymes in medical case :
Analytical
Manipulative
Therapeutic
Industrial
With those uses, the treatment of pharmaceutical enzymes range from
detection to defection
Used in supplements and medication
There are both good and bad side-effect
Analytical Uses
Enzymes used as detector :
Enzymes can be used to detect and measure amounts of glucose in blood
Amount of glucose in blood and urine is an indicator for diagnosis of diabetes
Detected by using enzyme glucose oxidase
Catalyzes reaction between glucose and oxygen to form gluconic acid
Biosensor measures the produced gluconic acid and then indicated by a color change.

Enzymes used to diagnose disorders :
Enzymes of liver, kidney and other types leak into blood during related disorders.
Thus the corresponding enzyme presence in high levels in blood than normal
range indicates the specific disorder.

Enzyme Use
Aldolase muscle disorders
Glutamate oxalo acetate transfrerase myocardial infarction
Iso-citrate dehydrogenase acute hepatitis
Acid phosphatase prostate cancer
Manipulative Uses
The goal : make an enzyme that has improved properties to improve health
Changes created through : exchange of amino acids, modifications in enzymes
structure, and adding short peptide domains (that stabilize the enzyme and target
the cell membrane or DNA).
Most common genetic alterations are with the creation of enzymes; introducing
point mutations, exchanging protein domains, and changing the structure
Enzymes can also be manipulated by :
engineering fusion proteins
enzyme hybrids
recruit established functions and properties from existing enzymes and
incorporate them into the engineered enzyme.
Creation of hybrid enzymes can expand the potential uses of natural enzymes.
Enzymes, or fragments of enzymes, could potentially serve as building blocks for
proteins capable of catalyzing reactions not observed in nature
Therapeutic Uses
Enzymes used to treat disorders :
In some disorders like low blood pressure, head or spinal injuries, there are chances of
formation of blood clots due to stagnation of blood inside the blood vessels.
These clots can be life threatening as they can get stuck in small vessels of brain and obstruct
blood flow.
These clots can be removed only by dissolution by enzymes that can break them such as
Streptokinase or Urokinase.

Enzymes used to assist metabolism :
In old patients, digestive capacity is low due to low secretion of digestive enzymes
Hence their digestive system cannot metabolize some food materials efficiently.
In such cases they can experience malnutrition, constipation etc.
To aid digestion, enzymes like Papain are administered orally after food for easier
digestion.
Therapeutic Uses
Enzyme supplements for enzyme deficiencies :
Many of us suffer from milk intolerance mainly due to a genetic lack of the correct enzyme
secretion.
Milk intolerance usually relates to an inability to digest lactose (milk sugar).
Prolactazyme contains lactase and other milk digesting enzymes treats lactose intolerance.

Enzymes used to assist drug delivery :
Some drugs need to penetrate deeper tissues for better action.
For this some enzymes are used along with drugs in intra-muscular injection
forms to help proper penetration of tissues.
One of such enzyme is Hyaluronidase (a natural human enzyme present in human
sperm to help sperm penetrate uterine tissue and fertilize with ova).
The same enzyme is manufactured by rDNA technology and administered along with
drugs to enable efficient drug delivery to the target site.
Some Important Therapeutic Enzymes
Factors Severely Reduces Potential Utility of Enzymes as
Therapeutic Agents for Treatment of Metabolic Diseases
They are too large to be distributed simply within the body's cells
This is why enzymes have not yet been successful applied to large number of human genetic
diseases
To overcome this problem : ex : enzymes covalently coupled to target-specific monoclonal
antibodies are being used to avoid non-specific side-reactions

Their effective lifetime within circulation may be only a matter of minutes
To overcome this problem : disguise using covalent modification, entrapment
of enzyme within artificial liposomes, synthetic microspheres, and red blood
cell ghosts
Although these methods are efficacious at extending the circulatory lifetime of
enzymes, they often cause increased immunological response and additionally
may cause blood clots
Factors Severely Reduces Potential Utility of Enzymes as
Therapeutic Agents for Treatment of Metabolic Diseases
Being generally foreign proteins to the body, they are antigenic and
can elicit an immune response which may cause severe and life-
threatening allergic reactions, particularly on continued use
To overcome this problem : disguising the enzyme as an apparently non-proteinaceous
molecule by covalent modification
Asparaginase, modified by covalent attachment of polyethylene glycol, has been shown
to retain its anti-tumour effect whilst possessing no immunosgenicity
Clearly the presence of toxins, pyrogens and other harmful materials within a
therapeutic enzyme preparation is totally forbidden
Effectively, this encourages the use of animal enzymes, in spite of their
high cost, relative to those of microbial origin

Application of Enzyme in Cancer Treatment
Asparaginase treatment of acute lymphocytic leukemia
Tumor cells are deficient in aspartate-ammonia ligase activity, which restricts their ability
to synthesize the normally non-essential amino acid L-asparagine. Therefore, they are
forced to extract it from body fluids
Action of the asparaginase doesnt affect functioning of normal cells which are able to
synthesize enough for their own requirements, but reduce free exogenous concentration
and so induces a state of fatal starvation in susceptible tumor cells
A 60% incidence of complete remission has been reported in a study of almost 6000
cases of acute lymphocytic leukaemia
The enzyme is administered intravenously
It is only effective in reducing asparagine levels within the bloodstream,
showing a half-life of about a day (in a dog)
This half-life may be increased 20-fold by use of polyethylene glycol-modified
asparaginase
Industrial Uses Drug Manufacture
Immobilized enzymes are used in manufacture of many drugs and antibiotics
This is possible as enzymes convert the pro-drug molecules to drugs or starting
material to drugs
In production of Antibiotics:
Immobilized pencillinase is used in converting Pencillin-G or V to 6-amino pencillinic acid.(6-
APA).
From this 6-APA Ampicillin is produced using immobilized enzyme pencillamidase.
Other examples include: Bacitracin, tyrosine, nikkomycin are manufactured using
suitable immobilized enzymes.

In Production of Steroids:
Prednisolone is produced from cortisone using immobilized enzyme obtained
from curcuria lanata.
Industrial Uses Drug Manufacture
To produce amino acids:
Immobilised L-aspartase-4-decarboxylase enzyme helps in conversion of L-Aspartic acid to L-
Alanine an amino acid.

In production of L-DOPA:
L-DOPA is a drug used in treatment of Parkinsonism. This can be produced by
using immobilized enzyme -tyrosinase.

In production of : Co-enzyme-A (Vit-B5), Pro-insulin, interleukin-2,
prostaglandins, monoclonal anti-bodies.

To produce medicinal plant derivatives like anthraquinone
(a glycoside to relieve constipation).


References
Bheem. 2014. 12 Applications of Enzymes in Medicine, Food, & Other Industries. Retrieved
from : http://www.rajaha.com/applications-enzymes-role/ (7 September 2014).
Chaplin, M. 2014. Enzyme Technology : Medical applications of enzymes. Retrieved from :
http://www1.lsbu.ac.uk/water/enztech/medical.html (7 September 2014).
Madison, Michelle, Nancy, Peter and Vivian. 2014. Applications of Enzymes in the
Pharmaceutical Industry. Retrieved from : http://www.loreescience.ca/site/SBI4U/bioch
emistry/Applications%20of%20Enzymes%20in%20the%20Pharmaceutical%20Industry
.pdf (7 September 2014).
Nixon, A. E., Ostermeier, M., & Benkovic, S. J. 1998. Hybrid enzymes: manipulating enzyme
design. Trends in Biotechnology, 16 : 258 - 264.
Vitolo, M. 2012. Industrial Uses of Enzymes. Retrieved from : http://www.eolss.net/sample-
chapters/c17/e6-58-05-12.pdf (7 September 2014).