Threonine, carbon atom reactions

Addition Reaction. The double bond of dehydroalanine and e-methyl dehydroalanine formed by the e-elimination reaction (Equation 6) is very reactive with nucleophiles in the solution. These may be added nucleophiles such as sulfite (44). sulfide (42), cysteine and other sulfhydryl compounds (20,47), amines such as a-N-acetyl lysine (47 ) or ammonia (48). Or the nucleophiles may be contributed by the side chains of amino acid residues, such as lysine, cysteine, histidine or tryptophan, in the protein undergoing reaction in alkaline solution. Some of these reactions are shown in Figure 1. Friedman (38) has postulated a number of additional compounds, including stereo-isomers for those shown in Figure 1, as well as those compounds formed from the reaction of B-methyldehydroalanine (from 6 elimination of threonine). He has also suggested a systematic nomenclature for these new amino acid derivatives (38). As pointed out by Friedman the stereochemistry can be complicated because of the number of asymmetric carbon atoms (two to three depending on derivative) possible. 

Figure 23.12. Bond Cleavage by PLP Enzymes. Pyridoxal phosphate enzymes lahilize one of three bonds at the a-carhon atom of an amino acid substrate. For example, bond a is labilized by aminotransferases, bond b by decarboxylases, and bond c by aldolases (such as threonine aldolases). PLP enzymes also catalyze reactions at the ()- and y-carbon atoms of amino acids. 

Threonine contains a sterically hindered and therefore less reactive hydroxy group. The O-acylation of unprotected threonine during coupling reactions is therefore less problematic, but can nevertheless occur. Noncoded hydroxy amino acids containing a secondary hydroxy group have a reactivity similar to threonine. These hydroxy amino adds contain an additional asymmetric center at the (3-carbon atom. In the case of reactions on the secondary hydroxy group, this center is accessible to racemization, e.g. threonine can be converted into allo-threonine. 

During the catabolism of fatty acids with an odd number of carbon atoms and the amino acids valine, isoleucine and threonine the resultant propionyl-CoA is converted to succinyl-CoA for oxidation in the TCA cycle. One of the enzymes in this pathway, methylmalonyl-CoA miitase, requires vitamin B12 as a cofactor in the conve sion of methylmalonyl-CoA to succinyl-CoA. The 5 -deoxyadenosine derivative of cobalamin is required for this reaction. 

The non-enzymic dephosphorylation of O-phosphorothreonine which is brought about by pyridoxal in aqueous media has been investigated and a mechanism for the reaction has been proposed (Scheme 2). Copper(ii) and oxovanadium(iv) ions exert a strong catalytic effect and the dephosphorylation proceeds with C—O fission. The initial formation of a Schiff base may occur, followed by the loss of a proton from the -carbon atom of the threonine. 0-Phosphoro-a-methylserine, which does not possess an a-proton, does not dephosphorylate readily in aqueous solution. 

Davies L. Functional and stereochemical specificity at the carbon atom of substrates in threonine dehydratase-catalyzed a.P elimination reactions. J Biol Chem 1979 254 4126-4131. 

Evidence from several lines of investigation indicated a relationship between L-aspartic acid and L-threonine. Studies with isotopically labeled acetate in yeast and bacteria showed that the distribution of label in the 4 carbon atoms of aspartate was the same as found in threonine. Both aspartate and homoserine were found to suppress incorporation of labeled CO2 into threonine, and the label of aspartate was found to appear in a corresponding position in threonine. Mutants of Neurospora and E. coli were found to use homoserine to form threonine other mutants accumulated homoserine, and in E. coli it was found that aspartate was converted to homoserine. In Lactobacilli threonine was found to minimize an aspartic acid requirement. All of these findings support a scheme of reversible reactions ... 

Beta-elimination reactions have been observed in a number of proteins. This reaction occurs primarily at alkaline pH conditions. Abstraction of the hydrogen atom from the alpha-carbon of a cysteine, serine, threonine, phenylalanine, or lysine residue leads to racemization or loss of part of the side chain and the formation of dehydroalanine (26). 

The glycine-dependent aldolases contain a cofactor pyridoxal phosphate (PLP). Binding of glycine to it as an imine enables the deprotonation necessary for the carbon-carbon bond forming reaction, with pyridine acting as an electron sink. The subsequent 100% atom efficient reaction with an aldehyde establishes the new bond and two new stereocenters (Scheme 5.30). Of all the glycine-dependent aldolases only L-threonine aldolase (LTA) is commonly used [40, 43, 52]. 

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