Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

Chapter 12
Diagnostic Enzymology of Domestic
Animals
Walter E. Hoffmann
Department of Veterinary Pathobiology
College of Veterinary Medicine
University of Illinois, Urbana, Illinois
Philip F. Solter
Department of Veterinary Pathobiology
College of Veterinary Medicine
University of Illinois, Urbana, Illinois
I. INTRODUCTION
II. HISTORY OF CLINICAL ENZYMOLOGY
III. FACTORS AFFECTING SERUM ENZYME ACTIVITY
A. Organ Mass and Enzyme Tissue Concentration
B. Cell Location
C. Mechanisms of Release of Cytoplasmic Enzymes or
Other Protein Biomarkers from Cells to Blood
D. Mechanisms of Release of Membrane-Bound Enzymes
E. Blood Clearance Rates of Enzymes
F. Enzyme Induction
IV. SPECIFIC ENZYMES
A. Alanine Aminotransferase
B. Aspartate Aminotransferase
C. Sorbitol Dehydrogenase
D. Glutamate Dehydrogenase
E. Gamma Glutamyltransferase
F. Alkaline Phosphatase
G. Lipase
H. Amylase
I. Trypsin and Trypsinogen
J. Creatine Kinase
K. Other Enzymes
V. FUTURE OF SERUM ENZYMOLOGY
REFERENCES
I . INTRODUCTION
The detection of proteins in serum by their catalytic activity
as a reporter of tissue damage is a cornerstone of medical
laboratory analyses ( Rej, 1998 ).
Clinical enzymology is the discipline that studies and
tests enzyme activity in serum, plasma, urine, or other body
fluids for the purpose of helping to establish the diagnosis
and prognosis of disease and to screen for abnormal organ
function. Although not the subject of this chapter, it should
be noted that some enzymes are also of major importance as
analytical reagents. This chapter first explores the universal
factors affecting changes in enzyme content of bodily fluids
and then delves into specific details relevant to particular
enzymes. Discussion of basic concepts in enzymology, such
as enzyme structure, kinetics, or analysis, is limited to those
that are of clinical relevance or that add insight into interpreting
changes in body fluid enzyme activity. Additional
information regarding enzyme structure and enzyme kinetics
can be found in numerous biochemistry texts as well as clinical
texts such as Tietz Fundamentals of Clinical Chemistry
( Burtis and Ashwood, 2001 ) and the previous edition of this
book. In addition, the methodology of the various enzyme
assays can be found in the literature provided by the vendors
of enzyme assay reagents.
II . HISTORY OF CLINICAL ENZYMOLOGY
Although the presence of enzymes in cells and plasma was
first recognized in the 1800s, the development of clinical
enzymology began after the introduction of an assay
for serum amylase by Wohlgemuth in 1908 and the report
in 1916 that serum amylase activity in blood and urine was
a reliable test for pancreatic disorders ( Rosenfeld, 1999 ).
This finding was followed in 1927 by the discovery of
alkaline phosphatase (ALP) in bone and the description of
serum alkaline phosphatase as a diagnostic test ( Rosenfeld,
1999 ). The development and marketing by Sigma Chemical
Company in St. Louis in the 1950s of simplified enzyme
assays in kit form, such as aspartate and alanine aminotransferases,
and an ALP assay that used p-nitrophenylphosphate
as substrate (Technical Bulletin 104), were major factors in
their routine clinical use and encouraged additional studies
in diagnostic enzymology ( Berger, 1993 ; Bessey et al. ,
1946 ; Reitman and Frankel, 1957 ). In addition to assay
reagent development, an equally significant contribution to
the development of clinical enzymology was the invention
by Leonard Skeggs of a multichannel autoanalyzer that was
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