CHAPTER
Enzymes III: Clinical Applications
Enzymes are used clinically in three principal ways:
1. As indicators of enzyme activity or enzyme
concentration in body fluids (e.g., serum and urine) in
the diagnosis and prognosis of various diseases;
2. As analytical reagents in the measurement of activity
of other enzymes or nonenzyme substances (e.g.,
substrates, proteins, and drugs) in body fluids; and
3. As therapeutic agents.
8.1 Diagnosis and Prognosis of Disease
Enzyme assays employed in the diagnosis of diseases are
one of the most frequently used clinical laboratory proce-
dures. The most commonly used body fluid for this pur-
pose is serum, the fluid that appears after the blood has clot-
ted. The liquid portion of unclotted blood is called
plasma.
Serum is used for many enzyme assays because the prepa-
ration of plasma requires addition of anticoagulants (e.g.,
chelating agents) that interfere with some assays. Enzymes
in circulating plasma are either
plasma-specific
or
non-
plasma-specific.
Plasma-specific enzymes are normally
present in plasma, perform their primary function in blood,
and have levels of activity that are usually higher in plasma
than in tissue cells. Examples are those enzymes involved
in blood clotting (e.g., thrombin), fibrinolysis (e.g., plas-
min), and complement activation, as well as cholinesterase
(also called pseudocholinesterase or choline esterase II to
distinguish it from the acetylcholinesterase of nervous tis-
sue; see Chapter
6
) and ceruloplasmin. These enzymes are
synthesized mainly in the liver and released into the cir-
culation at a rate that maintains optimal steady-state con-
centrations. Hereditary enzyme defects or impaired liver
function can cause suboptimal levels. For example, defi-
ciency of thrombin or plasmin can cause defective blood
coagulation or fibrinolysis, respectively. Cholinesterase
deficiency can cause prolonged muscle paralysis when
succinylcholine is administered as an adjunct to anes-
thesia to produce skeletal muscle relaxation. Succinyl-
choline, a structural analogue of acetylcholine, competes
with acetylcholine receptors at the motor end-plate of the
neuromuscular junction and brings about depolarization
that leads to muscle relaxation. The effect of succinyl-
choline is terminated through the enzymatic action of
plasma cholinesterase but is not significantly altered by
acetylcholinesterase at the neuromuscular junction. Mea-
surement of plasma cholinesterase before surgery may
prevent this adverse effect.
Non-plasma-specific
enzymes
are intracellular en-
zymes normally present in plasma at minimal levels or at
concentrations well below those in tissue cells. Their pres-
ence in plasma is normally due to turnover of tissue cells,
but they are released into the body fluids in excessive con-
centrations as a result of cellular damage or impairment
of membrane function. Tissue injury and impairment of
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