2. Enzymes are critical to the functioning of most cellular
systems
Because of their importance, the mutation,
overproduction, underproduction, or deletion of a
single critical enzyme can lead to severe disease.
More than 3000 human enzymes have been identified
and named.
enzyme committee (EC) of the International Union of
Biochemistry and Molecular Biology (IUBMB)
recommended the classification of enzymes into six
groups.
EC 1.11.1.6 = catalase
EC 5.3.1.5 = chimozinGad, Shayne Cox, ed. Handbook of pharmaceutical biotechnology. Vol. 2. John Wiley & Sons, 2007.
Okafor, Nduka. Modern Industrial Microbiology. Science Publishers. Enfield NH, USA, 2007.
3. 1.Oxidoreductases catalyze a variety of oxidation-reduction reactions.
Common names include dehydrogenase, oxidase, reductase
and catalase.
2.Transferases catalyze transfers of groups (acetyl, methyl, phosphate, etc.).
Common names include acetyltransferase, methylase, protein
kinase, and polymerase. The first three subclasses play major
roles in the regulation of cellular processes.
3.Hydrolases catalyze hydrolysis reactions where a molecule is split into two
or more smaller molecules by the addition of water.
Some examples are: Proteases: Proteases split protein
molecules. They are further classified by their optimum pH as
acid, alkaline or neutral.
4.Lyases catalyze the cleavage of C-C, C-O, C-S and C-N bonds by means
other than hydrolysis or oxidation. Common names include
decarboxylase and aldolase.
5.Isomerases catalyze atomic rearrangements within a molecule. Examples
include rotamase, protein disulfide isomerase (PDI), epimerase
and racemase.
6.Ligases catalyze the reaction which joins two molecules. Examples
include peptide synthase, aminoacyl-tRNA synthetase, DNA
ligase and RNA ligase.
Okafor, Nduka. Modern Industrial Microbiology. Science Publishers. Enfield NH, USA, 2007.
4. Enzymes as drugs
Gad, Shayne Cox, ed. Handbook of pharmaceutical biotechnology. Vol. 2. John Wiley & Sons, 2007.
5. Most enzyme pharmaceuticals in current use
belong to the hydrolase class such as galsulfase
and agalsidase
Hence, most enzyme drugs are used as enzyme
replacement therapies (ERT) for relatively rare,
inborn errors of metabolism (IEMs)
As a result, many enzyme therapeutics fall under
the FDA’s Orphan Drug Designation
However, a few enzyme therapies can also be used
to treat much more common conditions such as
cancer, heart attacks, and stroke
Gad, Shayne Cox, ed. Handbook of pharmaceutical biotechnology. Vol. 2. John Wiley & Sons, 2007.
7. a therapeutic enzyme was described as
part of replacement therapies for
genetic deficiencies in the 1960s by de
Duve
The concept of the
therapeutic enzyme has
been around for at least
40 years.
In 1987, the first recombinant enzyme
drug, Activase1 (alteplase;
recombinant human tissue
plasminogen activator), was approved
by the Food and Drug Administration
(FDA).
This ‘clot-buster’ enzyme
is used for the treatment
of heart attacks caused
by the blockage of a
coronary artery by a clot
This was the second
recombinant protein drug to
be marketed (the first
genetically engineered drug
was insulin in 1982)
Since then at least 16 other enzyme
drugs have been introduced into the
marketplace
Vellard, Michel. "The enzyme as drug: application of enzymes as pharmaceuticals." Current opinion in biotechnology 14.4 (2003): 444-
450.
8. 1990
Adagen (pegadamase bovine)
a form of bovine adenosine deaminase
(ADA) treated with polyethylene glycol (PEG)
approved to treat patients afflicted with a type of severe
combined immunodeficiency disease (SCID), which is caused
by the chronic deficiency of ADA.
First therapeutic enzyme
approved by the FDA under the
Orphan Drug Act
was passed in 1983 in the United States to
encourage pharmaceutical companies to
develop treatments for diseases affecting
only small numbers of people (less than 200
000)
first successful application of
an enzyme therapy for an
inherited disease
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
Vellard, Michel. "The enzyme as drug: application of enzymes as pharmaceuticals." Current opinion in biotechnology 14.4 (2003): 444-
450.
9. Vellard, Michel. "The enzyme as drug: application of enzymes as pharmaceuticals." Current opinion in biotechnology 14.4 (2003): 444-
450.
Jazz pharmaceuticals
intensenutrition
10. Vellard, Michel. "The enzyme as drug: application of enzymes as pharmaceuticals." Current opinion in biotechnology 14.4 (2003): 444-
450.
biocentury
Sanofi aventis
Bayer schering pharma
Genzyme
11. Gad, Shayne Cox, ed. Handbook of pharmaceutical biotechnology. Vol. 2. John Wiley & Sons, 2007.
Genzyme
12. Gad, Shayne Cox, ed. Handbook of pharmaceutical biotechnology.
Vol. 2. John Wiley & Sons, 2007.
1.Biomarine pharmaceuticals
2.Genzyme
3.Medra services
Dr. kade
13. Gad, Shayne Cox, ed. Handbook of pharmaceutical biotechnology. Vol. 2. John Wiley & Sons, 2007.
Abbot labratories
14. The Future of Enzyme Biopharmaceuticals
Some of the most active work has been in the area of lysosomal
storage diseases.
there are now several enzyme pharmaceuticals that are entering
phase II and phase III trials to treat several fatal or debilitating
syndromes associated with sugar metabolism or sugar catabolism
example acid maltase
Pompe’s disease
genetic deficiency of
the acid maltase
enzyme
breaks down
glycogen
In the absence of acid
maltase
infantile glycogen
storage disease
type 2 (GSD-II
Glycogen accumulates to toxic levels in
cardiac and skeletal muscles
causing the muscles to
waste away
Vellard, Michel. "The enzyme as drug: application of enzymes as pharmaceuticals." Current opinion in
biotechnology 14.4 (2003): 444-450.
15. challenges
delivery of the proteins to the right tissues
enormous cost and the sometimes questionable
benefits or small improvements to patient
quality of life
Vellard, Michel. "The enzyme as drug: application of enzymes as pharmaceuticals." Current opinion in biotechnology 14.4 (2003):
444-450.