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

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 -> -trypsin
further AA removal -> other forms eg -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

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:

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

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

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 -,-,-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-Hodgkins 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

Tissue plasminogen activator (tPA)

myocardial infarction, ischaemic stroke, certain pulmonary embolisms

DNA-ase
liquefy mucopurulent secretions in bronchopulmonary disease
from bovine pancreas in 1956 (dornase)
now recombinant human for cystic fibrosis

Imiglucerase
analog of human -glucocerebrosidase
Type I Gaucher disease

N-acetyl-galactosamine-4-sulfase
mucopolysaccharadosis

Alpha-L-iduronidase
mucopolysaccharadosis I

-glucosidase
Pompe disease (rare)

Alpha-1-antitrypsin
alpha-1-antitrypsin deficiency (emphysema, liver)

enzyme mixture coeliac disease (gluten)