The measurement of the activities or concentrations of selected enzymes in serum is a long-established aid to clinical diagnosis and prognosis. The enzymes found in serum can be divided into three categories based on the location of their normal physiological function:
• Serum-specific enzymes: The normal physiological function of these enzymes is based in serum. Examples include the enzymes associated with lipoprotein metabolism and with the coagulation of blood.
• Secreted enzymes: These are closely related to the serum-specific enzymes. Examples include pancreatic lipase and salivary amylase.
• Non-serum-specific enzymes: These enzymes have no physiological role in serum. They are released into the extra-cellular fluid and consequently appear in serum as a result of normal cell turnover or more abundantly as a result of cell membrane dam age, cell death or morphological changes to cells such as those in cases of malignancy. Their normal substrates and/or cofactors may be absent or in low concentrations in serum.
Serum enzymes in this third category are of the greatest diagnostic value. When a cell is damaged, the contents of the cell are released over a period of several hours with enzymes of the cytoplasm appearing first, since their release is dependent only on the impairment of the integrity of the plasma membrane. The release of these enzymes following cell membrane damage is facilitated by their large concentration gradient, in excess of a thousandfold, across the membrane. The integrity of the cell membrane is particularly sensitive to events that impair energy production, for example by the restriction of supply of oxygen. It is also sensitive to toxic chemicals, including some drugs, microorganisms, certain immunological conditions and genetic defects. Enzymes released from cells by such events may not necessarily be found in serum in the same relative amounts as were originally present in the cell. Such variations reflect differences in the rate of their metabolism and excretion from the body and hence of differences in their serum half-lives. This may be as short as a few hours (intestinal alkaline phosphatase, glutathione S-transferase, creatine kinase) or as long as several days (liver alkaline phosphatase, alanine aminotransferase, lactate dehydrogenase).
The clinical exploitation of non-serum-specific enzyme activities is influenced by several factors:
• Organ specificity: Few enzymes are unique to one particular organ, but some enzymes are present in much larger amounts in some tissues than in others. As a consequence, the relative proportions (pattern) of a number of enzymes found in serum are often characteristic of the organ of origin.
• Isoenzymes: Some clinically important enzymes exist in isoenzyme forms and in many cases the relative proportion of the isoenzymes varies consider ably between tissues so that measurement of the serum isoenzymes allows their organ of origin to be deduced.
• Reference ranges: The activities of enzymes present in the serum of healthy individuals are invariably smaller than those in the serum of individuals with a diagnosed clinical condition such as liver disease. In many cases, the extent to which the activity of a particular enzyme is raised by the disease state is a direct indicator of the extent of cellular damage to the organ of origin.
• Variable rate of increase in serum activity: The rate of increase in the activity of released enzymes in serum following cell damage in a particular organ is a characteristic of each enzyme. Moreover, the rate at which the activity of each enzyme decreases towards the reference range following the event that caused cell damage and the subsequent treatment of the patient is a valuable indicator of the patient’s recovery from the condition.
The practical implications of these various points to the applications of diagnostic enzymology are illustrated by its use in the management of heart disease and liver disease.
