Development of Diagnostic Enzymology

At the beginning of this century, clinics began to measure enzymes in body fluids to diagnose diseases. For example, Wohlgemuth determined urine amylase (AMY) as early as 1908 to diagnose acute pancreatitis. In the 1930s, alkaline phosphatase (ALP) was clinically used to diagnose skeletal diseases. Later, it was found that many liver and gall bladder diseases, especially when obstructive jaundice appears, this enzyme is often significantly increased. These enzymes became routine test items in clinical laboratories at that time. Until the 1960s, ALP was still the most frequently measured enzyme in the world. However, before the 1950s, enzyme measurement accounted for only a small part of the routine work of the laboratory.

The real development of diagnostic enzymes began with the continuous monitoring of enzyme activity concentration by spectrophotometry in the 1950s. It can measure many enzymes that cannot be measured with the old "fixed time method" and is used to diagnose diseases. The results showed that the sensitivity of lactate dehydrogenase (LD), aspartate aminotransferase (AST) and α-hydroxybutyrate dehydrogenase (HBDH) in the diagnosis of acute myocardial infarction (AMI) far exceeded that of other diagnostic methods. In the early 1960s, it was affirmed that creatine kinase (CK) increased in diagnosis of AMI earlier than the above enzymes, and the specificity was also high. At present, this enzyme has replaced ALP as the most frequently measured enzyme in the world. At the same time, it was found that alanine aminotransferase (ALT) and AST are not only highly sensitive to hepatitis diagnosis, but also significantly increased as early as the early stage of hepatitis and jaundice.

These achievements aroused the widespread interest and attention of clinical and laboratory workers at that time. They have carried out a lot of clinical and experimental work, tried and evaluated the clinical significance of hundreds of enzyme determinations, of which about ten enzymes have become important measurement items commonly used in the laboratory. Enzyme determination accounts for about 1/4 to 1/2 of the current total workload of clinical chemistry.

With extensive application and research, it has also been found that the specificity of the total enzyme activity concentration measurement for disease diagnosis is far from being as high as people initially expected. Since the 1970s, scholars have gradually focused their attention on the determination of isozymes, and found that the diagnosis of CK-MB and LD1 is more specific than the above total enzymes. CK-MB has become a recognized "gold index" for the diagnosis of AMI. The determination of these two isozymes has also become a mandatory test item in major hospitals.

Since the 1980s, it has been found that there may be changes after isozymes in tissues enter body fluids. For example, Ck-MM can be further divided into Ck-MM1, MM2, and MM3, and Ck-MB can be divided into MB1 and MB2. It is superior to CK total enzyme and isoenzyme in the diagnosis of AMI, and has become a research hotspot in clinical enzymology.

For a long time, the clinical understanding of the mechanism of serum enzyme changes has been very simple: that is, diseased cells release high concentrations of enzymes in their cells into the blood. The greater the enzyme concentration gradient between the two, the greater the increase in serum enzymes. This is far from explaining various clinical phenomena. For example, the absolute amount of AST in the liver is about 4 times that of ALT, but in acute hepatitis ALT increases much more than AST. However, in chronic liver disease, especially cirrhosis, the blood AST is higher than ALT, which is obviously difficult to clarify from the above concentration gradient theory. We must fully understand the various factors that affect the changes in serum enzymes, as well as understand the classification of serum enzymes, because the different types of enzyme change patterns are different.