Enzymes pyruvate kinase isoenzymes

The multienzymic nature of pyruvate kinase has been investigated in detail in M. expansa (98), H. diminuta (117) and S. erinacei (240). These worms possess FBP-sensitive and FBP-insensitive pyruvate kinase isoenzymes. In H. diminuta, as many as five pyruvate kinase isoenzymes (for definition and usefulness, see Chapter 6) occur during development (Fig. 5.3) and it seems likely that differential expression of these different forms of the enzyme may help to control the specific composition of excreted end-products by the various life cycle stages. The nature and regulation of the end-products secreted in H. diminuta are discussed further below. 

Ponce E, Flores N, Martinez A, Valle F, Bolivar F. Cloning of the two pyruvate kinase isoenzyme structural genes from Escherichia coli the relative roles of these enzymes in pyruvate biosynthesis. J Bacteriol 1995 177 5719-5722. 

A different problem results from deficiency of enzymes of glycolysis such as phosphofructokinase (see Box 20-D), phosphoglycerate rnutase, and pyruvate kinase. Lack of one isoenzyme of phosphoglycerate rnutase in muscle leads to intolerance to strenuous exercise/ A deficiency in pyruvate kinase is one of the most common defects of glycolysis in erythrocytes and leads to a shortened erythrocyte lifetime and hereditary hemolytic anemia.s... 

Enzymes, measured in clinical laboratories, lor which kiis arc available include y-glutamyl transferase tGGT). alanine transferase (ALT), aldolase, cr-amylase, aspartate aminotransferase, creatine kinase and its isoenzymes, galactose-1-phosphate uridyl transferase, lipase, mutate dehydrogenase. 5 -nucleotidase. phosphuhexose isomerase. and pyruvate kinase. 

Several isoenzyme forms of pyruvate kinase are known (M.W. 190,000-250,000, depending on the source). Each is a homotetramer exhibiting catalytic properties consistent with the function of the tissue in which it occurs. Enzyme activity is dependent on K+ (which increases the affinity for phosphoenolpyruvate) and Mg +. 

All of the regulatory enzymes of glycolysis exist as tissue-specific isoenzymes, which alter the regulation of the pathway to match variations in conditions and needs in different tissues. For example, in the liver, an isoenzyme of pyruvate kinase introduces an additional regulatory site in glycolysis that contributes to the inhibition of glycolysis when the reverse pathway, gluconeogenesis, is activated. 

Fig. 22.12. Major sites of regulation in the glycolytic pathway. Hexokinase and phos-phofructokinase-1 are the major regulatory enzymes in skeletal muscle. The activity of pyruvate dehydrogenase in the mitochondrion determines whether pyruvate is converted to lactate or to acetyl Co A. The regulation shown for pyruvate kinase only occurs for the liver (L) isoenzyme.

The second rate-limiting step in glycolysis is the conversion of PEP to pyruvate, catalysed by pyruvate kinase. There are a number of isoenzymes of pyruvate kinase, and they have been classified according to their properties and their tissue distribution in mammals. The avian enzymes have then been fitted to the mammalian classification where appropriate (Table 3.4). Those enzymes present in tissues that carry out gluconeogenesis generally have more... 

Pyruvate kinase, in general, is inhibited by high concentrations of ATP, alanine, acetyl-CoA and long-chain fatty acids. Thus the affinity of the enzyme for its substrate is lowered when energy requirements can be satisfied by other means. Conversely at low [ATP], the affinity of pyruvate kinase for phosphoenolpyruvate (PEP) increases to support the substrate-level phosphorylation of ADP even at low [PEP] because of its inherent instability. The liver isoenzyme is activated by fructose 1,6-bisphosphate so that pyruvate kinase activity is coordinated with variations in... 

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