Pyruvate kinase regulation

See also Enzymes of Glycolysis, Molecules of Glycolysis, Glycolysis, Pyruvate Kinase Regulation, Pyruvate Kinase Isozymes, Substrate Level Phosphorylation, Phosphoglycerate Kinase, Action of Glucagon... 

Pyruvate kinase possesses allosteric sites for numerous effectors. It is activated by AMP and fructose-1,6-bisphosphate and inhibited by ATP, acetyl-CoA, and alanine. (Note that alanine is the a-amino acid counterpart of the a-keto acid, pyruvate.) Furthermore, liver pyruvate kinase is regulated by covalent modification. Flormones such as glucagon activate a cAMP-dependent protein kinase, which transfers a phosphoryl group from ATP to the enzyme. The phos-phorylated form of pyruvate kinase is more strongly inhibited by ATP and alanine and has a higher for PEP, so that, in the presence of physiological levels of PEP, the enzyme is inactive. Then PEP is used as a substrate for glucose synthesis in the pathway (to be described in Chapter 23), instead... 

Glycolysis is regulated by three enzymes catalyzing nonequilibrium reactions hexokinase, phosphoffuc-tokinase, and pyruvate kinase. 

M15. Mattevi, A., Bolognesi, M and Valentini, G., The allosteric regulation of pyruvate kinase. FEBS Lett. 389, 15-19(1996). 

The hormones glucagon, cortisol and insulin regulate the concentrations of some enzymes and hence their activities. These include glucokinase, pyruvate kinase and phospho-enolpyruvate carboxykinase. Most work has been carried out on the carboxykinase enzyme, for which it is known that glucagon and cortisol increase the concentration whereas insulin decreases it. These changes are brought about at the transcriptional level by changing the activity of transcription factors (Chapter 20). Since the hormones... 

Carrillo, J.J. Ibares, B. Esteban-Gamboa, A. Feliu, J.E. Involvement of both phosphatidylinositol 3-kinase and p44/p42 mitogen-activated protein kinase pathways in the short-term regulation of pyruvate kinase L by insulin. Endocrinology, 142, 1057-1064 (2001)... 

Three glycolytic enzymes are subject to allosteric regulation hexoldnase IV, phosphofructokinase-1 (PFK-1), and pyruvate kinase. 

Yamada, K. Noguchi, T. (1999) Nutrient and hormonal regulation of pyruvate kinase gene expression. Biochem J. 337, 1—11. Detailed review of recent work on the genes and proteins of this system and their regulation. 

Feed-forward regulation In liver, pyruvate kinase is activated by fructose 1,6-bisphosphate, the product of the phosphofructo-kinase reaction. This feed-forward (instead of the more usual feedback) regulation has the effect of linking the two kinase activities increased phosphofructokinase activity results in elevated levels of fructose 1,6-bisphosphate, which activates pyruvate kinase. 

Thomson, J. and Torchia, D. A. 1984. Use of 31P nuclear magnetic resonance spectroscopy of 14C fluorography in studies of glycolysis and regulation of pyruvate kinase... 

Doiron, B., Cuif, M.H., Kahn, A. and Diaz-Guerra, M.J. (1994) Respective roles of glucose, fructose, and insulin in the regulation of the liver-specific pyruvate kinase gene promoter. J. Biol. Chem., 269, 10213-10216. 

Lefrancois-Martinez, A.M., Diaz-Guerra, M.J., Vallet, V., Kahn, A. and Antoine, B. (1994) Glucose-dependent regulation of the L-pyruvate kinase gene in a hepatoma cell line is independent of insulin and cyclic AMP. FASEB. J., 8, 89-96. 

Regulation of pyruvate kinase, pyruvate carboxylase and PEP carboxykinase... 

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. 

Metabolic regulation in Moniezia expansa (Cestoda) the role of pyruvate kinase. International Journalfor Parasitology, 2 333— 40. 

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