pharmaceutical enzymes

ByMohammad pooya naghshbandi

Microbial biotechnologistAt

University of Tehran

Recombinant pharmaceutical enzymes

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 = catalaseEC 5.3.1.5 = chimozin

Gad, Shayne Cox, ed. Handbook of pharmaceutical biotechnology. Vol. 2. John Wiley & Sons, 2007.Okafor, Nduka. Modern Industrial Microbiology. Science Publishers. Enfield NH, USA, 2007.

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.

Enzymes as drugs

two important features

often bind and act on their targets with great affinity and specificity

enzymes are catalytic and convert multiple

target molecules to the desired products

Gad, Shayne Cox, ed. Handbook of pharmaceutical biotechnology. Vol. 2. John Wiley & Sons, 2007.

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


http://www.kyrobio.eu/Anton_Glieder.htmlDiCosimo, Robert, et al. "Industrial use of immobilized enzymes." Chemical Society Reviews 42.15 (2013): 6437-6474.

http://www.kyrobio.eu/Anton_Glieder.html

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.

1990Adagen (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



Jazz pharmaceuticals

intensenutrition


biocentury

Sanofi aventis

Bayer schering pharma

Genzyme


Genzyme


1.Biomarine pharmaceuticals2.Genzyme

3.Medra services

Dr. kade


Abbot labratories

The Future of Enzyme BiopharmaceuticalsSome 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

enzymebreaks 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 towaste away


challenges

delivery of the proteins to the right tissues

enormous cost and the sometimes questionable benefits or small improvements to patient quality of life
