Lecture 7

Enzymes in clinical practice

By Dr Nivan Zoheiry
 Overview
 Reactions in human body is mediated
by enzymes, which are Globular
protein catalysts that increase the rate
of the reactions without being changed
in the overall process
 Clinical Uses of Enzymes

Enzymes are used clinically in three
principal ways:

1-In diagnosis and prognosis of various
disease

2-As analytical reagents in the measurement
of activity of other enzyme or non-enzyme
substances

3-As therapeutic agents
 Isoezymes

Isoezymes: are different formes of given
enzyme having the same catalytic activity,
but differ in some physical or chemical
properties.

Thus each isoenzyme will act on the same
substrate and give the same product.

LDH, ALP and CPK are enzymes having
isoenzymes.
 Enzymes as Therapeutic Agents
 Some enzymes are used in treatment of certain
diseases.
 1-Digestive enzymes,
 2-Anti-inflammatory agents that reduce swelling
and help clear away debris. Papain also has
analgesic and anti-inflammatory action.
 3-Pancreatic enzymes do have a powerful anti-
cancer effect on pancreatic cancer and multiple
myleoma.
 4- Streptokinase is a enzyme produced by
beta-haemolytic streprococus and is used
as an effective clot-dissolving medication in
some cases of myocardial infarction and
pulmonary embolism
 Defective enzyme can result from genetic
mutation, or infection by bacteria or
viruses ,The development of Enzyme
replacement therapy (ERT) has brought
hope to individuals with some rare, inherited
diseases.
 ERT
 ERT is not a cure for any condition; but it
treats the deficient enzyme activity.
 ERT is safe and effective; however, it is
costly
 Diagnosis and Prognosis
 Destruction of cells. Tissue damage or
necrosis resulting from injury or disease is
accompanied by increase in levels of
enzymes.
 By measuring the level of certain enzymes
in plasma it helpes in the diagnosis and
prognosis of many diseases

Isozymes of lactate dehydrogenase (LDH) are
used in MI diagnosis
 Creatinine kinase (CK) used MI and Muscle
disorders
Enzymes which may indicate alterations in
liver health.
 Alanine Aminotransferase: ALT
Cell damage will cause elevations of A-LT
due to leakage. The elevation of the enzyme
correlates with the number of cells
damaged.
 Falling levels of ALT may indicate recovery
or may indicate a failing number of
functional liver cells.
 Rapid increases in ALT may indicate an
acute process, while slow increases may
indicate bile duct obstruction.
Aspartate Aminotransferase: AST
enzyme seen in the liver, heart, kidney,
skeletal muscle and brain, AST elevations and
ALT elevations should parallel each other in
liver disease
Alkaline Phosphatase ALP
This enzyme is present in many tissues,
therefore it is not very specific in liver disease,
but it appears very early in the progress of liver
disease, therefore it is considered quite
sensitive
 Site-directed mutagenesis

Site-directed mutagenesis has been widely
used in the study of protein functions. 

There are many approaches were a mutation
being added to DNA strand in a certain site

Site-directed mutagenesis (modification of
amino acid sequence of known enzymes) is
used for design new drug therapy
 Ribozymes and catalytic
antibodies

Abzymes - Abzymes are antibodies that
catalyze specific chemical reactions, i.e.
function as enzymes.
 Antibodies by definition have evolved to
recognise and bind to the ground states of
the molecules they are specific to. In
contrast, enzymes have binding sites that
preferentially bind to the transition state of
their substrate molecules
 For this reason abzymes are not produced
naturally
 Ribozymes

Ribozymes are RNA molecules with catalytic
activity.
 And concerned with RNA metabolism as
splicing
 In higher eukaryotic cells, show that RNA
can act as an enzyme. This has
revolutionized thinking about enzyme action
and the origin of life itself.