Proton glutamine

The tertiary structure of glutamate racemase has already been resolved and it has also been shown that a substrate analog glutamine binds between two cysteine residues. These data enabled us to predict that the new proton-donating amino acid residue should be introduced at position 74 instead of Gly for the inversion of enantioselectivity of the decarboxylation reaction. 

Theberge, J., Bartha, R., Drost, D. J. et al. Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am. J. Psychiat. 159 1944-1946, 2002. 

Theberge,J.,Al-Semaan,Y.,Williamson, P.C. etal. Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS. Am. J. Psychiat. 160 2231-2233, 2003. 

The mechanism of hydrolysis of cysteine peptidases, in particular cysteine endopeptidases (EC 3.4.22), shows similarities and differences with that of serine peptidases [2] [3a] [55 - 59]. Cysteine peptidases also form a covalent, ac-ylated intermediate, but here the attacking nucleophile is the SH group of a cysteine residue, or, rather, the deprotonated thiolate group. Like in serine hydrolases, the imidazole ring of a histidine residue activates the nucleophile, but there is a major difference, since here proton abstraction does not appear to be concerted with nucleophilic substitution but with formation of the stable thiolate-imidazolium ion pair. Presumably as a result of this specific activation of the nucleophile, a H-bond acceptor group like Glu or Asp as found in serine hydrolases is seldom present to complete a catalytic triad. For this reason, cysteine endopeptidases are considered to possess a catalytic dyad (i.e., Cys-S plus H-His+). The active site also contains an oxyanion hole where the terminal NH2 group of a glutamine residue plays a major role. 

Figure 8.29 The initial reactions of glutamine metabolism in kidney, intestine and cells of the immune system. The initial reaction in all these tissues is the same, glutamine conversion to glutamate catalysed by glutaminase the next reactions are different depending on the function of the tissue or organ. In the kidney, glutamate dehydrogenase produces ammonia to buffer protons. In the intestine, the transamination produces alanine for release and then uptake and formation of glucose in the liver. In the immune cells, transamination produces aspartate which is essential for synthesis of pyrimidine nucleotides required for DNA synthesis otherwise it is released into the blood to be removed by the enterocytes in the small intestine or by cells in the liver.

Note that the side-chains of glutamine and asparagine are not basic these side-chains contain amide functions, which do not have basic properties (see Section 4.5.4). The heterocyclic ring in tryptophan can also be considered as non-basic, since the nitrogen lone pair electrons form part of the aromatic jt electrons and are unavailable for bonding to a proton (see Section 11.8.2). 

Brignon et al. (1969) demonstrated that the maximum acid-binding capacity of /3-lactoglobulin D is the same as that of the other variants. The curves are identical at pH 4.0. At pH 6.5, one less proton is dissociated in the titration of the D variant than with the B variant, as would be predicted from the substitution of a glutamine residue for a glutamic acid residue in B. The anomalous carboxyl group observed in the other variants is also detected in the D variant. 

Many mutant forms of nitrogenase have been investigated. Substitutions of His 195, Lys 191, and Gly 69 of the a chain affect reactions with various substrates.45 54 For example, the mutant obtained by substitution of His 195, whose imidazole forms an N-H--S hydrogen bond to a central bridging sulfide atom of FeMo-co (Fig. 24-3A), with glutamine (H195Q mutant) reduces N2 only very slowly.45 However, it still reduces both acetylene and protons.27/44a 45b Thus, it may be that different modes of substrate binding are needed for the individual steps of Eq. 24-10. 

Why did nature waste an ATP in glutamine biosynthesis The lone pair of electrons on an ammonia could have attacked the y-carbonyl group of a glutamate. Subsequent elimination of an oxide ion and release of a-proton from the nitrogen would produce a glutamine without the consumption of an ATP. 

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