Larry H. Bernstein, MD, FCAP, Author and Curator Isozymes An example of an isozyme is glucokinase, a variant of hexokinase which is not inhibited by glucose 6-phosphate. Its different regulatory features and lower affinity for glucose (compared to other hexokinases), allows it to serve different functions in cells of specific organs, such as control of insulinrelease by the beta cells of the pancreas, or initiation ofglycogen synthesis by liver Both of these processes must only occur when glucose is abundant,or problems occur. Isozymes or Isoenzymes are proteins with different structure which catalyze the same reaction. Frequently they are oligomers made with different polypeptide chains, so they usually differ in regulatory mechanisms and in kinetic characteristics. From the physiological point of view, isozymes allow the existence of similar enzymes with different characteristics, “customized” to specific tissue requirements or metabolic conditions. One example of the advantages of having isoenzymes for adjusting the metabolism to different conditions and/ or in different organs is the following: Glucokinase and Hexokinase are typical examples of isoenzymes. In fact, there are four Hexokinases: I, II, III and IV. Hexokinase I is present in all mammalian tissues, and Hexokinase IV, aka Glucokinase, is found mainly in liver, pancreas and brain. Both enzymes catalyze the phosphorylation of Glucose: Glucose + ATP —–à Glucose 6 (P) + ADP Hexokinase I has a low Km and is inhibited by glucose 6 (P). Glucokinase is not inhibited by Glucose 6 (P) and his Km is high. These two facts indicate that the activity of glucokinase depends on the availability of substrate and not on the demand of the product. Since Glucokinase is not inhibited by glucose 6 phosphate, in conditions of high concentrations of glucose this enzyme continues phosphorylating glucose, which can be used for glycogen synthesis in liver. Additionally, since Glucokinase has a high Km, its activity does not compromise the supply of glucose to other organs; in other words, if Glucokinase had a low Km, and since it is not inhibited by its product, it would continue converting glucose to glucose 6 phosphate in the liver, making glucose unavailable for other organs (remember that after meals, glucose arrives first to the liver through the portal system). The enzyme Lactate Dehydrogenase is made of two (H- and M-) sub units, combined in different Permutations and Combinations depending on the tissue in which it is […]![]()
