Lactate dehydrogenase isozyme forms

The structure of an enzyme can also vary within a person, since different genes may encode enzymes that catalyse the same reaction. These enzymes are known as isozymes. Isozymes are often specific for different types of tissue. For example, lactate dehydrogenase (LDH) is produced in two forms, the M-type (muscle) and the H-type (heart). The M-type is predominates in tissue subject to anaerobic conditions, such as skeletal muscle and liver tissue, whereas the H-type predominates in tissue under aerobic conditions, such as the heart. Isozymes may be used as a diagnostic aid. For example, the presence of H-type LDH in the blood indicates a heart attack, since heart attacks cause the death of heart muscle with the subsequent release of H-type LDH into the circulatory system. 

Isozymic forms of lactate dehydrogenase in different tissues catalyze the interconversions of pyruvate and lactate. 

Enzymes which exist in multiple forms within a single species of organism or even in a single cell are called isoenzymes or isozymes. Such multiple forms can be detected and separated by gel electrophoresis of cell extracts. Since they are coded by different genes, they differ in amino acid composition and thus in their isoelectric pH values. Lactate dehydrogenase is an example for the isoenzymes which occur as five different forms in the tissues of the human and other vertebrates. All the five isozymes catalyze the same reaction. 

The M4 isozyme functions optimally in the anaerobic environment of hard-working skeletal muscle, whereas the H4 isozyme does so in the aerobic environment of heart muscle. Indeed, the proportions of these isozymes are altered in the development of the rat heart as the tissue switches from an anaerobic environment to an aerobic one (Figure 10.16A). Figure 10.16B shows the tissue-specific forms of lactate dehydrogenase in adult rat tissues. 

The major facilitator (MF) superfamily of transporters (p. 457) isozymic forms of lactate dehydrogenase (p. 469)... 

I 43. A 65-year-old obese male presents with severe indigestion and chest pain after a spicy meal. A lactate dehydrogenase (LDH) level obtained to evaluate possible myocardial infarction is normal, but the laboratory recommends that LDH isozymes be performed. The managing physician knows that lactate dehydrogenase is composed of two different polypeptide chains arranged in the form of a tetramer. Assuming that all possible combinations of the different polypeptide chains occur, how many isozyme forms of lactate dehydrogenase must be measured ... 

Eszes, R. B. Sessions, R. L. Brady, Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase, Proteins Struct., Puna., Genet., 43, 175-185 (2001). 

Lactate dehydrogenase (LDH) is a tetrameric protein consisting of two types of subunits, called M and H, which have small differences in amino acid sequence. Different molecular forms of an enzyme are called isoenzymes or isozymes. 

Historically, measurements of the isozymes of creatine kinase (CK) and lactate dehydrogenase (LD) have been used for the detection of myocardial injury. These are enzymes of intermediary metabolism found in both cardiac and skeletal muscle, although in different forms reflecting the different metabolic and functional properties of these tissues. There are also significant amounts of CK in nervous tissue and smooth muscle, whereas LD is expressed in most tissues (Aktas et al. 1993). 

Serum levels of lactate dehydrogenase (LDH) were formerly used to diagnose an acute Ml. LDH is present in cells as a tetramer of four identical, or nearly identical, subunits. Each subunit is a separate polypeptide chain with a molecular weight of 35 kD (approximately 35,000 g/mole). These subunits are present as two isoforms, the H isoform (for heart) and the M isoform (for skeletal muscle). Although the heart produces principally the H4 form (four H subunits combined into a tetramer) and skeletal muscles produce principally the M4 isoform, the heart, skeletal muscle, and other tissues produce several intermediate combinations (e.g., H3M, HjMj). These tetrameric isoforms all have similar activities, but the individual monomeric subunits are inactive. Measurements of LDH isozymes in the serum are no longer used for diagnosis of a recent Ml because the enzyme is large, released slowly, and the isozyme pattern is not as specific for the heart as is CK. 

The possible isozymes of lactate dehydrogenase. The symbol M refers to the dehydrogenase form that predominates in skeletal muscle, and the symbol H refers to the form that predominates in heart (cardiac) muscle. 

The five classical isozymes of lactate dehydrogenase (LDH) arise from combinations of the two restricted definitions described earlier. LDH isozymes consist of two genetically distinct polypeptide chains, A (or M for muscle type) and B (or H for heart type), which form varying combinations of tetrameric structures (90). 

---