Application of Enzymes in Health Care Industry
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Joan Christie W. (11320120002)
Ong. Nicky Alexander (11320120006)
Aristya Wismoyo (11320120017)
Danika Augusta S. (11320120019)
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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
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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
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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
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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.
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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.
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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
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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
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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
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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.
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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.
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Some Important Therapeutic Enzymes
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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
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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
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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 doesn’t 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
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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.
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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 “β-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).
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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).
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