Isozymes, or isoenzymes, are enzymes that differ in amino acid sequence yet catalyze the same reaction. Typically, these enzymes display different kinetic parameters, such as K_M, or respond to different regulatory molecules. They are encoded by different genes, which usually arise through gene duplication and divergence. Isozymes can often be distinguished from one another by physical properties such as electrophoretic mobility. Isoform is a more generic term used when the protein in question is not an enzyme.

The existence of isozymes permits the fine-tuning of metabolism to meet the needs of a given tissue or developmental stage. Consider the example of lactate dehydrogenase (LDH), an enzyme that catalyzes a step in anaerobic glucose metabolism and glucose synthesis. Human beings have two isozymic polypeptide chains for this enzyme: the H isozyme is highly expressed in heart muscle and the M isozyme is expressed in skeletal muscle. The amino acid sequences are 75% identical. Each functional enzyme is tetrameric, and many different combinations of the two isozymic polypeptide chains are possible. The H₄ isozyme, found in the heart, has a higher affinity for substrates than does the M₄ isozyme. The two isozymes also differ in that high levels of pyruvate allosterically inhibit the H₄ but not the M₄ isozyme. The other combinations, such as H₃ M, have intermediate properties. We will consider these isozymes in their biological context in Chapter 16.

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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 change throughout the development of the rat heart as the tissue switches from an anaerobic environment to an aerobic one (Figure 10.15A). Figure 10.15B shows the tissue-specific forms of lactate dehydrogenase in adult rat tissues. Essentially all of the enzymes that we will encounter in later chapters, including allosteric enzymes, exist in isozymic forms.

The appearance of some isozymes in the blood is a sign of tissue damage, useful for clinical diagnosis. For instance, an increase in serum levels of H₄ relative to H₃M is an indication that a myocardial infarction, or heart attack, has damaged heart-muscle cells, leading to the release of cellular material.