Deamidation reaction proteins

Deamidation, isomerization and racemization. These three reactions are common degradation pathways of proteins and peptides. These reactions are especially prevalent for peptides containing asparagine (Asn) and glutamine (Gin) residues. In the deamidation reaction, the Asn or Gin amide... 

Ammonia is formed in the cell or by bacteria during various deamidization reactions of amino acids. A certain quantity (ca. 25%) of ammonia is produced in the intestine by bacteria or through enzymatic action in the intestinal mucosa during protein degradation. This mean value of intestinal ammonia production is elevated under normal conditions as a result of the increased consumption of meat or fish and reduced during a predominantly lacto-vegetarian protein diet. Production of ammonia is raised by physical work a similar effect is possible in constipation. 

Asparagyl residues tend to be more susceptible to deamidation than glutamyl residues. Further, the deamidation reaction is strongly sequence-specific in model peptides with the half life of the -Asn-Pro- sequence being 100-fold greater than that of -Asn-Gly-. To some extent these observations can also be used on proteins that take the structural steiic factors and nearby amino acid residues into consideration. 

Studies on the protein deamidation in food systems has recently been of great interest to the food industry. This is due to the fact that the deamidation reaction changes functional properties of protein such as solubility, emulsion property, and foaming ability... 

Deamidation of proteins is important for improving functional properties of the product under mild reaction conditions. But enzymatic deamidation of proteins has not had real attention until recently. Kato et al. [155] developed a method for enzymatic deamidation of food proteins by treatment with proteases at pH 10. Salt and disulfide reducing agents have little effect on soy protein deamidation. Heat treatment and proteolysis of soy proteins are the major factors affecting deamidation [156]. 

Apart from protein sequence and structure, temperature, pH, and the type of buffers can all influence the deamidation and isoaspartate formation. The effect of temperature on the deamidation reaction rate generally follows the Arrhenius law. Deamidation activation energies around 21-22kcalmoH have been reported for two model peptides under alkaline conditions [19, 20]. The deamidation is also subject to general acid/base catalysis, as evidenced by an increase in deamidation rate with an increase in buffer concentration [2]. 

Deamidation in peptides and proteins generally require the participation of a water molecule to go to completion. In peptides, there are minimal obstructions to water access to the labile amide. However, the more stable protein structures may limit access of water to the amide groups and so influence the rates of any deamidation reactions. Deamidation rates of Asn and Gin residues on the surface of the proteins will not be limited by water access, while those that occur in the interior of proteins may be. Such a limitation will be determined by the static protein structure and by the frequency with which buried Asn and Gin are exposed to solvent during rapid dynamic changes in the structure due to thermal motion. 

Artificial protein modification reactions can be induced, for example, deamidation of proteins. 

The influence of secondary structure on reactions of deamidation has been confirmed in a number of studies. Thus, deamidation was inversely proportional to the extent of a-helicity in model peptides [120], Similarly, a-hel-ices and /3-turns were found to stabilize asparagine residues against deamidation, whereas the effect of /3-sheets was unclear [114], The tertiary structure of proteins is also a major determinant of chemical stability, in particular against deamidation [121], on the basis of several factors such as the stabilization of elements of secondary structure and restrictions to local flexibility, as also discussed for the reactivity of aspartic acid residues (Sect. 6.3.3). Furthermore, deamidation is markedly decreased in regions of low polarity in the interior of proteins because the formation of cyclic imides (Fig. 6.29, Pathway e) is favored by deprotonation of the nucleophilic backbone N-atom, which is markedly reduced in solvents of low polarity [100][112],... 

An example of this effect is provided by ribonuclease A (RNase A). At pH 8 and 37°, the rate of deamidation of Asn67 was more than 30-fold lower in the native than in the unfolded protein [111]. Deamidation of the native RNase A was also ca. 30-fold slower than of an octapeptide whose sequence is similar to that of the deamidation site, although the reaction mechanisms were similar [108][123],... 

T. Geiger, S. Clarke, Deamidation, Isomerization, and Racemization at Asparaginyl and Aspartyl Residues in Peptides Succinimide-Linked Reactions That Contribute to Protein Degradation , J. Biol. Chem. 1987, 262, 785 - 794. 

Geiger T. and Clarke S. (1987), Deamidation, isomerization and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation, J. Biol. Chem. 262, 785-794. 

Proteins, peptides, and other polymeric macromolecules display varying degrees of chemical and physical stability. The degree of stability of these macromolecules influence the way they are manufactured, distributed, and administered. Chemical stability refers to how readily the molecule can undergo chemical reactions that modify specific amino-acid residues, the building blocks of the proteins and peptides. Chemical instability mechanisms of proteins and peptides include hydrolysis, deamidation, racemization, beta-elimination, disulfide exchange, and oxidation. Physical stability refers to how readily the molecule loses its tertiary and/or sec-... 

Proteins are subject to a variety of chemical modification/degradation reactions, viz. deamidation, isomerization, hydrolysis, disulfide scrambling, beta-elimination, and oxidation. The principal hydrolytic mechanisms of degradation include peptide bond... 

A common problem with lenses is cataract, a term that describes any loss of opacity or excessive coloration. There are many kinds of cataract, most of which develop in older persons.560 562 Since lens proteins are so long-lived deamidation of some asparagine occurs. However, the reactions are slow. One of the asparagines in a crystalline has a half-life of 15-20 years, and some glutamines are undamaged after 60 years.575... 

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