Several enzymes have important therapeutic, medical or pharmaceutical uses. In this article, those enzymes used therapeutically will be described.
ENZYMES
Several enzymes have important
therapeutic, medical or pharmaceutical uses (Table 26.3).
In this article, those enzymes used therapeutically will be described.
i) Streptokinase and
streptodornase
Mammalian blood will clot spontaneously
within minutes if allowed to stand, but if left to stand longer the clot begins
to dissolve as a result of the action of a proteolytic enzyme called plasmin.
Plasmin is normally present as its inactive precursor, plasminogen. Certain
strains of streptococci were found to produce a substance that is capable of
activating plasminogen (Figure 26.3),
a phenomenon that suggested a potential use in liquefying clots, i.e.
fibrinolysis. This substance, called streptokinase, was isolated and determined
to be an enzyme.
Streptokinase is administered by intravenous or intra-arterial infusion
in the treatment of thromboembolic disorders, e.g. pulmonary embolism, deep
vein thrombosis and arterial occlusions. It is also used in emergency medicine
for acute myocardial infarction.
A second enzyme, streptodornase, present in streptococcal culture
filtrates, was observed to liquefy pus. Streptodornase is a deoxyribonuclease
that breaks down deoxyribonucleoprotein and DNA, both constituents of pus,
resulting in a reduction in pus viscosity. Streptokinase and streptodornase
together have been used to facilitate drainage by liquefying blood clots and/or
pus in the chest cavity. The combination can also be applied topically to
wounds that have excessive suppuration.
Streptokinase and streptodornase are isolated following growth of
non-pathogenic streptococcal producer strains in media containing excess
glucose. They are obtained as a crude mixture from the culture filtrate and can
be prepared relatively free of each other. They are commercially available as
either streptokinase injection or as a combination of streptokinase and
streptodornase.
ii) L-Asparaginase
L-Asparaginase, an enzyme derived
from E. coli or Erwinia chrysanthemi,
converts l-asparagine to aspartic acid and ammonia. In contrast to normal
tissue, some tumours have an essential requirement for l-asparagine and
L-asparaginase has therefore been investigated as a selective cancer
chemotherapeutic. Although L-asparaginase showed early promise in a variety of
experimentally induced tumours, it has primarily found utility in humans for
the treatment of acute lymphoblastic leukaemia and occasionally for myeloid
leukaemia.
iii) Neuraminidase
Many tumours escape immune surveillance
through mechanisms including the masking of cell surface antigens by, for
example, N-acetylneuraminic (sialic) acid residues. Neuraminidase,
derived from Vibrio cholerae, has been used
experimentally to increase the immunogenicity of tumour cells by stripping
sialic acid residues from the outer surface of certain tumour cells resulting
in presentation of tumour-specific antigens to the host immune system. In
laboratory animals, administration of neuraminidase-treated tumour cells was
found to be effective against a variety of mouse leukaemias. Preliminary investigations
in acute myelocytic leukaemia patients have suggested that treatment of tumour
cells with neuraminidase in combination with conventional chemotherapy may
increase remission rates.
iv) β-Lactamases
β-Lactamase enzymes, whilst presenting
a considerable therapeutic challenge due to their ability to confer bacterial
resistance by inactivating penicillins and cephalosporins, are nevertheless
useful in the sterility testing of certain antibiotics and, prior to culture,
in inactivating various β-lactams in blood or urine samples in patients
undergoing therapy with these drugs. One other important therapeutic
application is in the rescue of patients presenting symptoms of a severe
allergic reaction following administration of a β-lactamase-sensitive penicillin.
In such cases, a highly purified penicillinase obtained from B. cereus has been administered either
intramuscularly or intravenously and in combination with other supportive
measures such as adrenaline and antihistamines.
Related Topics
TH 2019 - 2024 pharmacy180.com; Developed by Therithal info.