Transcript S2 L6 Enzymes

S2 L6 Pharmaceutical uses of
enzymes
Anna Drew
Enzymes
• catalyse (speed up) chemical reactions
• involved in most processes in a biological cell
• proteins
• specific
• activity affected by
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other molecules (inhibitors)
temperature
chemical environment (pH)
concentration of substrate
• wide range of uses
• household products
• pharmaceutical
Papain
• Cystine protease hydrolase enzyme
• Source:
– Papaya (Carica papaya)
– Mountain papaya (Vasconcellea cundinamarcensis)
• latex from the neck of fruit is collected, dried to form crude material
• extraction process to purify to powder or liquid form
• also contains chymopapain
• Use: anti-inflammatory and digestive
– meat tenderiser
• breaks down tough meat fibres
• long traditional use in S.American
– teeth whitening agent
• In some toothpastes
– contact lens cleaner
– jellyfish, bee/wasp stings, stingray wounds (home remedy)
• breaks down protein toxins in the venom
– wound debriding
– digestive aid
Bromelain
• One of two proteases
• Stem bromelain
• Fruit bromelain
• History:
• 1891 isolated
• 1957 introduced as therapeutic supplement
• 13th most widely used herbal medicine in Germany
• Source: Bromeliaceae family
• eg pineapple Ananas comosus – commerically from the stem
• Thailand – after fruit harvesting stem stripped, crushed, pressed to get juice,
concentrated
• Use: meat tenderising
– anti-inflammatory: sports injury, trauma, arthritis
– digestive problems, phlebitis, sinusitis
– platelet clumping, blood clots in arteries
• A/E: may show cardiotonic activity (doses of up to 1840mg)
– nausea, vomiting, diarrhoea, menorrhagia, possible allergenic reaction
Trypsin, Chymotrypsin
• Serine proteases or endopeptidases
– ‘proteolytic’
- hydrolyse peptide bonds
– modify the electrostatic environment of the serine
• chymotrypsin -> phenylalanine, tryptophan and tyrosine residues
• trypsin -> aspartic acid residue (in catalytic pocket) which attracts and
stabilises lysine and arginine
– both have to be activated
– inactive form trypsinogen
• removal of hexapeptide from terminal end -> β-trypsin
• further AA removal -> other forms eg α-trypsin
– cystic fibrosis – trypsin deficiency
• Source: bovine pancreas (purified)
• crystallised from pancreatic juice
• introduced as medicinals mid-20th century
• ? dosage forms not available in US
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Uses: (* modern, rest historical)
– Topical* (ointment, dusts, dressing, gel capsule to insert into fistulas):
• cleaning necrotic wounds
– attack dead tissue
– not living which has inhibitory enzymes
• cleaning suppurating wounds
– decreases pus
• burns – reduces tissue destruction and free radical production
– Oral:
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with buccal tablets
pancreatic supplement
to dissolve blood clots (microbial form)*
combined with papain in many cancers to reduce disease and radiation/chemotherapy
symptoms*
• (in baby foods to pre-digest it*)
– Inhalation (spray): to reduce tenacious sputum
– I/M: anti-inflammatory (pancreatic form)
– Injectable:
• cataract and eye lens surgery* – ocular inflammation
• phlebitis
• traumatic wounds
– Chymotrypsin
– more anti-inflammatory activity
– used for sporting wounds
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C/I: liver disease, blood clotting
Pancreatin
• Source: porcine pancreas
• crude form used since before 1870
• Use: for reduced exocrine secretion
– pancreatic enzyme supplements - pancrelipase
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cystic fibrosis
pancreatectomy
chronic pancreatitis
pancreatic cancer (if obstructs outflow)
• C/I: hypersensitivity to porcine products
• Products: standardised for lipase, amylase and protease activity
• fat, carbohydrate and protein digestion
• Counselling:
– inactivated by gastric acid
• best taken with food (immediately before or after)
– H2antagonists one hour before or concurrent antacids can reduce gastric acidity
– no chewing enteric-coated preparations
– inactivated by heat
• avoid mixing with hot (temperature) food
– adequate hydration with high-dose formulations
• Pepsin
– Source: porcine gastric muscosa
– Use: (protease)
• gastric hypochlorhydria
• deficiency of gastric enzymes
• dyspepsia
• Diastase
– Refers to α-,β-,γ-amylase
• first discovered in 1833 in malt solution
– Source:
• Animal: eg porcine
• Vegetable: mould (Aspergillus oryzae – taka-diastase), malt, bacteria
– Action: catalyses breakdown of starch to maltose
– Use: overindulgence in starchy foods
• Pectinase
– Action: refers to enzymes that break down pectin
• polysaccharide substrate found in plant cell walls
• eg polygalacturonase
– Source: extracted from fungi
• eg Aspergillus niger
– Use: processing involving degradation of plant material
• to speed up extraction of juice from fruit eg apples
• retting – obtaining fibres of eg flax, jute, hemp
Urokinase
• Source: isolated from human urine
• Action:
– convert plasminogen to plasmin which catalyses the breakdown
of fibrin
• Use:
– deep vein thrombosis, pulmonary embolism
– thrombosed IV cannulae, central venous catheters and
haemodialysis shunts
– peripheral arterial thromboembolism
• A/E: bleeding, allergic reactions, cholesterol embolism
• C/I: bleeding disorders, history of bleeding
Asparaginase
• Source: isolated from E.coli
– recombinant form expressed in the bacteria
• Action:
– catalyses the conversion of the AA L-asparagine to L-aspartic acid
reducing availability of L-asparagine to leukaemic cells
• Use:
– ALL acute lymphoblastic leukaemia
– some subtypes of non-Hodgkin’s lymphoma
• A/E: allergy, pancreatitis, coagulopathy
• C/I: previous allergic reaction to it, pancreatitis
• Counselling: increase fluid intake and avoid dehydration
Hyaluronidase
• Source:
– buffalo leeches
• leeches of the sub-family Hirudinariinae
• eg Hirudinaria manillensis, Poecilobdella granulosa
– ? sheep
– now human recombinant
• Action: degrades or hydrolyses hyaluronic acid
– part of the interstitial barrier (connective tissue)
• Use: speeds dispersion and delivery of drugs
– ophthalmic surgery with local anaesthetics
– renders tissues more easily permeable to injected fluids
• eg by subcutaneous injection – hypodermoclysis
– extravasation
• (inadvertant leakage of the drug out of a vein into surrounding tissue)
Many other recombinants
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Tissue plasminogen activator (tPA)
– myocardial infarction, ischaemic stroke, certain pulmonary embolisms
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DNA-ase
– liquefy mucopurulent secretions in bronchopulmonary disease
• from bovine pancreas in 1956 (dornase)
• now recombinant human for cystic fibrosis
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Imiglucerase
– analog of human β-glucocerebrosidase
– Type I Gaucher disease
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N-acetyl-galactosamine-4-sulfase
– mucopolysaccharadosis
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Alpha-L-iduronidase
– mucopolysaccharadosis I
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α-glucosidase
– Pompe disease (rare)
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Alpha-1-antitrypsin
– alpha-1-antitrypsin deficiency (emphysema, liver)
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enzyme mixture – coeliac disease (gluten)