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chapter
8
Enzymes III: Clinical Applications
membrane function can be caused by diminished oxygen
supply (e.g., myocardial infarction), infection (e.g., hep-
atitis), and toxic chemicals. Proliferation of cells, with
consequent increased turnover, can also raise levels in
plasma of enzymes characteristic of those cells (e.g., ele-
vation of serum acid phosphatase in prostatic carcinoma).
Table 8-1 lists clinically useful enzymes and their tissue
of origin. Intracellular enzymes are essentially confined
to their cells of origin. A few are secretory enzymes that
are secreted by some selected tissue (salivary gland, gas-
tric mucosa, or pancreas) into the gastrointestinal tract,
where they participate in digestion of food constituents
(Chapter 12). Plasma levels of secretory enzymes increase
when their cells of origin undergo damage or membrane
impairment or when the usual pathways of enzyme secre-
tion are obstructed. For example, large amounts of pancre-
atic amylase and triacylglycerol lipase (commonly known
as
lipase)
enter the blood circulation in patients suffering
from pancreatitis. These enzymes can digest the pancreas
itself and surrounding adipose tissue in a process known
as
enzymatic necrosis
(death of tissue cells).
The diagnosis of organ disease is aided by measure-
ment of a number of enzymes characteristic of that tis-
sue or organ. Most tissues have characteristic enzyme
patterns (Table 8-2) that may be reflected in the rela-
tive serum concentrations of the respective enzymes in
disease. The diseased tissue can be further identified by
determination of the isoenzyme pattern of one of these
enzymes (e.g., lactate dehydrogenase, creatine kinase) in
the serum, since many tissues have characteristic isoen-
zyme distribution patterns for a given enzyme. For exam-
ple, creatine kinase (CK) is a dimer composed of two sub-
units, M (for muscle) and B (for brain), that occur in three
isoenzyme forms, BB(CKj), MB(CK2) and MM(CK3),
which catalyze the reversible phosphorylation of crea-
tine with adenosine triphosphate (ATP) as the phosphate
donor:
CK
Creatine + ATP — phosphocreatine +
ADP
(adenosine diphosphate)
This
reaction
provides
ATP for muscle contraction
(Chapter 21). Skeletal muscle contains predominantly
CK3, whereas heart muscle (myocardium) contains CK
3
and CK2. Serum normally contains a small amount of
CK
3
derived predominantly from skeletal muscle. De-
tection of CK
2
in serum (in an appropriate clinical set-
ting) is strongly suggestive of myocardial damage. Since
an abnormal isoenzyme level may occur with apparently
normal total activity of the enzyme, determination of the
isoenzyme concentration is essential in the diagnostic
enzymology.
TABLE 8-1
Tissues o f Origin o f Some Diagnostically Important
Serum Enzymes
Enzyme
Principal Tissue Source
Acid phosphatase
Prostate
Alanine aminotransferase
Liver
(glutamate pyruvate
transaminase)
Alcohol dehydrogenase
Liver
Alkaline phosphatase
Bone, intestinal mucosa,
hepatobiliary system,
placenta, kidney
Amylase*
Pancreas, salivary glands
Arginase
Liver
Aspartate aminotransferase
Heart and skeletal muscle,
(glutamate oxaloacetate
liver kidney, brain
transaminase)
Ceruloplasmin
Liver
Cholinesterase
Liver
Chymotrypsin(-ogen)*
Pancreas
Creatine kinase
Skeletal and heart muscle,
brain
Fructose-bisphosphate
Skeletal and heart muscle
aldolase
y
-Glutamyltransferase
Kidney, hepatobiliary
system, prostate,
pancreas
Glutamate dehydrogenase
Liver
Isocitrate dehydrogenase
Liver
Lactate dehydrogenase
Skeletal and heart muscle,
liver, kidney, erythro-
cytes, pancreas, lungs
Leucine aminopeptidase
Hepatobiliary system,
intestine, pancreas, kidney
Ornithine carbamoyl-
Liver
transferase
Pepsin(-ogen)*
Gastric mucosa
Prostatic specific antigen
Prostate
(a serine proteinase)
Sorbitol dehydrogenase
Liver
Triacylglycerol lipase*
Pancreas
(lipase)
Trypsin(-ogen)*
Pancreas
’Secretary enzymes.
Factors Affecting Presence and Removal
of Intracellular Enzymes from Plasma
Many factors are taken into consideration in the clinical
interpretation of serum enzyme levels. Membrane perme-
ability changes and cell destruction affect the release of
