Y-carboxylation

Gla y-carboxyl glutamic acid residues. (...) are used to bring sequences into alignment for greater homology. 

Calculate the pH at which the y-carboxyl group of glutamic acid is two-thirds dissociated. 

FIGURE 18.35 Formation of THF from folic acid by the dihydrofolate reductase reaction. The R group on these folate molecules symbolizes the one to seven (or more) glutamate units that folates characteristically contain. All of these glutamates are bound in y-carboxyl amide linkages (as in the folic acid structure shown in the box A Deeper Look Folic Acid, Pterins, and Insect VFingis). The one-carbon units carried by THF are bound at N, or at or as a single carbon attached to both... 

In bone, three proteins have been described which are vitamin K-dependent, osteocalcin (bone Gla protein), matrix Gla protein (MGP), and protein S. Osteocalcin is synthetized by osteoclasts, regulated by the active form of vitamin D, calcitriol. Its capacity to bind calcium needs a vitamin K-dependent y-carboxylation of three glutamic acid residues. The calcium binding capacity of osteocalcin indicates a possible role in bone mineralization, but its exact function is still unclear. However, it is widely used as a serum marker for bone mineralization. Protein S, mainly a coagulant, is also vitamin-K dependent and synthesized in the liver. Children with... 

For activity, factors II, VII, IX, and X and proteins C and S require vitamin K-dependent y-carboxylation of certain glutamate residues, a process that is inhibited by the anticoagulant warfarin. 

The levels of vitamin K-dependent coagulation factors are physiologically low in neonates. Absence of vitamin K impairs y-carboxylation, and the inactive precursors of factors II, VII, IX, and X accumulate in the plasma, unable to bind calcium and cell membranes. Consequently, the precursor levels may decline further, impairing coagulation and potentially leading to VKDB. 

Figure 2.11 y-Carboxylation of glutamate residues (Glu) yields y-carboxyglutamate (Gla), whereas (3-hydroxy lation of aspartate (Asp) yields (3-hydroxyaspartate (Hya) and (3-hydroxylation of asparagine (Asn) yields 3-hydroxyasparagine (Hyn)... 

Among the strategies used for the development of GST Pl-1 inhibitors is the modification of the GSH backbone to leverage its inherent affinity for GST Pl-1. One approach centered on the incorporation of a carbamate group as an isosteric replacement of the y-carboxylic Glu linkage in GSH. Synthesis and in vitro testing of 42 and 43 showed that this carbamate-replacement approach was not well tolerated [67]. 

Figure 1-10-3. Vitamin K-Dependent y-Carboxylation of Prothrombin During Translation...

Answer D. Phenyl hydantoins decrease the activity of vitamin K, which is required for the y-carboxylation of coagulation factors (11, VII, IX, X), as well as proteins C and S. 

Heating of foods rich in proteins may lead to formation of crosslinking isopeptide bonds between the S-NH2 group of lysine and the p- and y-carboxyl groups of aspartic and glutamic acid residues or their amides. 

It has been hypothesized that folate receptor-mediated endocytosis can be exploited for the selective delivery of drugs by covalent attachment to folate via its y-carboxyl group. This concept was primarily designed for the targeting of various biomolecules to solid tumours. For a... 

Glutamic acid is an example of an amino acid with an acidic side-chain. The pATa values are 2.19 (CO2H), 4.25 (Y-C02H), and 9.67 (NH2). Here, the y-carboxyl is more typical of a simple carboxylic acid. In strongly acidic solution, glutamic acid will... 

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