Phosphorylation of enzymes

Phosphorylation of enzymes to rapidly increase or decrease their activity. 

McDermott et al used rotational resonance, a then newly developed solid-state NMR method, for structural studies of an inhibited complex formed by reaction of D-alanine D-alanine ligase, ATP, and the aminoalkyl dipeptide analogue. The measured NMR coupling properties indicate that the two species are bridged in a P—O—P linkage, with a P—P through-space distance of 2.7 0.2 A. This work unambiguously demonstrated that the inactivation mechanism involves phosphorylation of enzyme-bound inhibitor by ATP to form a phos-phoryl-phosphinate adduct. ... 

A lot of biologic membrane systems and cellular organelles contain kinases, which transfer phosphate groups to proteins, especially to serine, threonine, and tyrosine residues. Self-phosphorylation of enzymes leading to acylphosphates or phosphoamides can be observed, too. With respect to their chemical stability, these phos-phoproteins are classified into acid-stable (alkali labile), hydroxyl-amine-sensitive, and acid labile. 

The phosphorylation of enzymes by specific protein kinases is a widespread mechanism for the regulation of enzyme activity. It represents a flexible and reversible means of regulation and plays a central role in signal transduction chains in eucaryotes. 

When the hormonal stimulus stops, the intracellular actions of cAMP are terminated by an elaborate series of enzymes. cAMP-stimulated phosphorylation of enzyme substrates is rapidly reversed by a diverse group of specific and nonspecific phosphatases. cAMP itself is degraded to 5 -AMP by several cyclic nucleotide phosphodiesterases (PDE Figure 2-13). Competitive inhibition of cAMP degradation is one way caffeine, theophylline, and other methylxanthines produce their effects (see Chapter 20). 

Hoving, H. Koning, J.H. Robillard, G.T. Escherichia coli phosphoenolpyruvate-dependent phosphotransferase system role of divalent metals in the dimerization and phosphorylation of enzyme I. Biochemistry, 21, 3128-3136 (1982)... 

Hormones that use 3, 5 -cyclic AMP (cAMP) as a second messenger stimulate a mechanism, resulting in the phosphorylation of enzymes. 

Glycogen mobilization is controlled hormonally by a metabolic cascade that is activated by cAMP formation and involves successive phosphorylations of enzyme proteins (Figure 13.18)... 

One of the important cellular responses to insulin is the reversal of glucagon-stimulated phosphorylation of enzymes. Mechanisms proposed for this action include the inhibition of adenylate cyclase, a reduction of... 

The eukaryotic cell cycle is tightly controlled by regulatory mechanisms that ensine faithful replication of the genome before cell division. These regulatory mechanisms, named cell-cycle checkpoints, are based, to a large extent, on the reversible phosphorylation of enzymes on serine/threonine residues, and the major control sites are Gl/S and G2/M phases. ° ° ... 

The Intermediate Phosphorylation of Enzyme. There are no known See Addendum at end of chapter. 

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