26767-88-4Relevant academic research and scientific papers
Metal ion inhibition of nonenzymatic pyridoxal phosphate catalyzed decarboxylation and transamination
Zabinski,Toney
, p. 193 - 198 (2007/10/03)
Nonenzymatic pyridoxal phosphate (PLP) catalyzed decarboxylations and transaminations have been revisited experimentally. Metal ions are known to catalyze a variety of PLP-dependent reactions in solution, including transamination. It is demonstrated here that the rate accelerations previously observed are due solely to enhancement of Schiff base formation under subsaturating conditions. A variety of metal ions were tested for their effects on the reactivity of the 2-methyl-2-aminomalonate Schiff bases. All were found to have either no effect or a small inhibitory one. The effects of Al3+ were studied in detail with the Schiff bases of 2-methyl-2-aminomalonate, 2-aminoisobutyrate, alanine, and ethylamine. The decarboxylation of 2-methyl-2-aminomalonate is unaffected by metalation with Al3+, while the decarboxylation of 2-aminoisobutyrate is inhibited 125-fold. The transamination reaction of ethylamine is 75-fold slower than that of alanine. Ethylamine transamination is inhibited 4-fold by Al3+ metalation, while alanine transamination is inhibited only 1.3-fold. Metal ion inhibition of Schiff base reactivity suggests a simple explanation for the lack of known PLP dependent enzymes that make direct mechanistic use of metal ions. A comparison of enzyme catalyzed, PLP catalyzed, and uncatalyzed reactions shows that PLP dependent decarboxylases are among the best known biological rate enhancers: decarboxylation occurs 1018-fold faster on the enzyme surface than it does free in solution. PLP itself provides the lion's share of the catalytic efficiency of the holoenzyme: at pH 8, free PLP catalyzes 2-aminoisobutyrate decarboxylation by ～1010-fold, with the enzyme contributing an additional ～108-fold.
SYNTHESIS OF (2R)- AND (2S)- -2-AMINO-2-METHYLMALONIC ACID: CHIRAL SUBSTRATES FOR SERINE HYDROXYMETHYLTRANSFERASE
Thomas, Neil R.,Gani, David
, p. 497 - 506 (2007/10/02)
(2R)- and (2S)--2-amino-2-methylmalonate, probes for the stereochemical course of the serine hydroxymethyltransferase reaction, have been synthesised from bis-lactim ethers derived from valine and alanine.Direct acylation of the anion with diethyl carbonate gave the N-ethoxycarbonyl derivative rather than the required ethyl ester.The 13C-labelled carboxyl group was therefore introduced via treatment of the anion with -acetyl chloride, followed by haloform oxidation.The resulting carboxylate salt was then esterified with methyl iodide, and the bis-lactither ring system was cleaved under acidic conditions to give the amino acid esters.Saponification and then separation by cation chromatography gave the title compounds.
