Reversible covalent modification

Histone acetylation is a reversible and covalent modification of histone proteins introduced at the e-amino groups of lysine residues. Histones and DNA form a complex - chromatin - which condenses DNA and controls gene activity. Current models interpret histone acetylation as a means to regulate chromatin activity. 

In mammalian cells, the two most common forms of covalent modification are partial proteolysis and ph osphorylation. Because cells lack the ability to reunite the two portions of a protein produced by hydrolysis of a peptide bond, proteolysis constitutes an irreversible modification. By contrast, phosphorylation is a reversible modification process. The phosphorylation of proteins on seryl, threonyl, or tyrosyl residues, catalyzed by protein kinases, is thermodynamically spontaneous. Equally spontaneous is the hydrolytic removal of these phosphoryl groups by enzymes called protein phosphatases. 

REVERSIBLE COVALENT MODIFICATION REGULATES KEY MAMMALIAN ENZYMES... 

The principal enzymes controlling glycogen metabolism—glycogen phosphorylase and glycogen synthase— are regulated by allosteric mechanisms and covalent modifications due to reversible phosphorylation and... 

Ghanges in the availability of substrates are responsible for most changes in metabolism either directly or indirectly acting via changes in hormone secretion. Three mechanisms are responsible for regulating the activity of enzymes in carbohydrate metabolism (1) changes in the rate of enzyme synthesis, (2) covalent modification by reversible phosphorylation, and (3) allosteric effects. 

Note that in some cases one may follow the time course of covalent E-A formation by equilibrium binding methods (e.g., LC/MS, HPLC, NMR, radioligand incorporation, or spectroscopic methods) rather than by activity measurements. In these cases substrate should also be able to protect the enzyme from inactivation according to Equation (8.7). Likewise a reversible competitive inhibitor should protect the enzyme from covalent modification by a mechanism-based inactivator. In this case the terms. S and Ku in Equation (8.7) would be replaced by [7r] and K respectively, where these terms refer to the concentration and dissociation constant for the reversible inhibitor. 

In the mid-1970s ubiquitin was found to be a covalent modifier of proteins [1]. At the time, it was quite surprising to find a protein that covalently modified another protein. Since then, the reversible covalent modification of proteins by other proteins is known to be commonplace and ubiquitin is used to covalently modify hundreds of proteins, often for the purpose of targeting them to the proteasome for degradation. 

The covalent modifications of histone tails such as acetylation, phosphorylation, and ubiquitination have been shown to be reversible. This reversibility help the cells to respond to these regulatory modifications and thereby, influence the gene expression. Methylation of histones however, has been considered to be a relatively stable and irreversible mark on histones. Nevertheless active turnover of methyl groups on histones do exist. One of the possible mechanism of removal of methyl... 

It is termed reversible, since the covalent modification that is catalysed by one enzyme is reversed by another enzyme. However, each individual reaction is irreversible. 

Carbohydrate detection is important for applications such as glucose monitors these are arguably one of the most successful and relevant biosensors. An interesting fluorescence recovery-type saccharide sensor based on the reactivity of carbohydrates with boronic acids was reported in 2002 [36]. Specifically, modification of the cationic viologen-linked boronic acid derivative 40 to a zwitterionic species 41 upon covalent and reversible reaction of boronic acid with monosaccharides (Scheme 1) can cause the dissociation of the ion-pair in-... 

The structural differences between euchromatin and heterochromatin are coor-dinately regulated by reversible covalent modification of the DNA or histones. 

Some Regulatory Enzymes Undergo Reversible Covalent Modification... 

Rapid alteration of the activities of enzymes is often accomplished by reversible covalent modification.39 47... 

Protein phosphatases. Most regulatory alterations in enzymatic activity are spontaneously reversible. The concentration of the allosteric effector soon drops and the covalent modifications are reversed so that the system relaxes to a state approximating the... 

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