Basis for the equilibrium constant in the interconversion of l-lysine and l-β-lysine by lysine 2,3-Aminomutase

Abstract

SUMMARYL-β-Lysine and β-glutamate are produced by the actions of lysine 2,3-aminomutase and glutamate 2,3-aminomutase, respectively. The pK a values compounds have been titrimetrically measured and are for L-β-lysine: pK 1 = 3.25 (carboxyl), pK 2 = 9.30 (β-aminium), and pK 3 = 10.5 (ε-aminium). For β-glutamate the values are pK 1 = 3.13 (carboxyl), pK 2 = 3.73 (carboxyl), and pK 3 = 10.1 (β-aminium). The equilibrium constants for reactions of 2,3-aminomutases favor the β-isomers. The pH-and temperature dependencies of K eq have been measured for the reaction of lysine 2,3-aminomutase to determine the basis for preferential formation of β-lysine. The value of K eq (8.5 at 37 °C) is independent of pH between pH 6 and pH 11; ruling out differences in pK-values as the basis for the equilibrium constant. The K eq -value is temperature-dependent and ranges from 10.9 at 4 °C to 6.8 at 65 °C. The linear van't Hoff plot shows the reaction to be enthalpy-driven, with ΔH° = −1.4 kcal mol −1 and ΔS° = −0.25 cal deg −1 mol −1 . Exothermicity is attributed to the greater strength of the bond C β -N β in L-β-lysine than C α -N α in L-lysine, and this should hold for other amino acids.

Kinetic and Spectroscopic Evidence of Negative Cooperativity in the Action of Lysine 2,3-Aminomutase

“…However, the equilibrium constants for the formation of β- l -lysine from l -lysine range from 7.2 to 10.8 depending on temperature between 21 and 37 °C, and for the reaction of glutamate 2,3-aminomutase, it is 15.7 at 37 °C . The values of these equilibrium constants are attributed to the greater enthalpic strength of the C−N bonds in β- l -lysine and β-glutamate than in l -lysine and l -glutamate, respectively . The greater strength of the β-C−N bonds is explained by the fact that these groups are flanked by sp 3 carbons on both sides, C2 and C4.…”

“…An experimental value of the equilibrium constant for the reaction of l -alanine is not available. However, the equilibrium constants for the formation of β- l -lysine from l -lysine range from 7.2 to 10.8 depending on temperature between 21 and 37 °C, and for the reaction of glutamate 2,3-aminomutase, it is 15.7 at 37 °C . The values of these equilibrium constants are attributed to the greater enthalpic strength of the C−N bonds in β- l -lysine and β-glutamate than in l -lysine and l -glutamate, respectively .…”

“…14 The values of these equilibrium constants are attributed to the greater enthalpic strength of the C-N bonds in β-L-lysine and β-glutamate than in L-lysine and L-glutamate, respectively. 33 The greater strength of the β-C-N bonds is explained by the fact that these groups are flanked by sp 3 carbons on both sides, C2 and C4. In L-lysine and L-glutamate, the R-C-N groups are flanked by sp 2 -C1 and sp 3 -C3.…”

Unusual Mechanism for an Aminomutase Rearrangement: Retention of Configuration at the Migration Termini

“…A general property considered of all amino acids is the greater strength of the C β -N bond over the C R -N bond (24), as observed for the lysine-2,3-aminomutase reaction. The free energy (∆G°≈ -1.4 kcal‚mol -1 ) was calculated to be considerably less than zero, and the forward reaction was assessed to be largely enthalpy-driven (24). However, in the PAM isomerization reaction, the product to substrate ratio of nearly 1.0 (cf.…”

Studies of viomycin, an anti-tuberculosis antibiotic: copper(ii) coordination, DNA degradation and the impact on delta ribozyme cleavage activity

“…The lower pK a value may be attributed to the amino group in the β-position, while the higher oneto the amino group in the ε-position. 27 The obtained constants, collected in Table 1, are apparently higher by a ca. 0.2 log unit than the respective values calculated for capreomycin.…”