Transamination equilibrium constant

In transamination, equilibrium constants are close to unity at best and the amino transfer from an a-amino acid to a ketone is strongly disfavored. To even worsen... 

Figure 11.3 is a flow model representing in extremely simple form the main relevant features of nitrogen metabolism. It is not difficult to propose a sufficient explanation why Bprot is isotopically heavier than the diet. We might expect that the net effect of transamination and deamination of amino acids is to remove isotopically lighter N (Macko et al. 1987). That is to say, we may expect that the equilibrium constant for the reaction ... 

Figure 29-3. Transamination. The reaction is freely reversible with an equilibrium constant close to unity.

Equilibrium of transamination reactions For most transamina tion reactions, the equilibrium constant is near one, allowing the reaction to function in both amino acid degradation through removal of a-amino groups (for example, after consumption of a protein-rich meal), and biosynthesis through addition of amino groups to the carbon skeletons of a-keto acids (for example, when the supply of amino acids from the diet is not adequate to meet the synthetic needs of cells). 

The major disadvantage of the transamination technology is an equilibrium constant K often near unity. As K 1 would limit the net conversion of substrates to around 50%, the key to efficient transamination technology lies in overcoming the problem of incomplete conversion of the 2-keto acid precursor to the desired amino... 

Although the utility of transaminases has been widely examined, one such limitation is the fact that the equilibrium constant for the reaction is near unity. Therefore, a shift in this equilibrium is necessary for the reaction to be synthetically useful. A number of approaches to shift the equilibrium can be found in the literature.53 124135 Another method to shift the equilibrium is a modification of that previously described. Aspartate, when used as the amino donor, is converted into oxaloacetate (32) (Scheme 19.21). Because 32 is unstable, it decomposes to pyruvate (33) and thus favors product formation. However, because pyruvate is itself an a-keto acid, it must be removed, or it will serve as a substrate and be transaminated into alanine, which could potentially cause downstream processing problems. This is accomplished by including the alsS gene encoding for the enzyme acetolactate synthase (E.C. 4.1.3.18), which condenses two moles of pyruvate to form (S)-aceto-lactate (34). The (S)-acetolactate undergoes decarboxylation either spontaneously or by the enzyme acetolactate decarboxylase (E.C. 4.1.1.5) to the final by-product, UU-acetoin (35), which is meta-bolically inert. This process, for example, can be used for the production of both l- and d-2-aminobutyrate (36 and 37, respectively) (Scheme 19.21).8132 136 137... 

Transamination reactions have equilibrium constants close to one. Therefore, the direction of a transamination reaction proceeds in large part as a function of the intracellular concentrations of the reactants. This means that transamination can be used not only for amino acid synthesis, but also for degradation of amino acids that accumulate in excess of need. The reaction here shows how transamination is used for degradation of amino acids. 

The a-keto adds of the above amino acids (except methionine) and also o-ketoglutarate were effective substrates for transamination. Study of the kinetic properties of this transaminase preparation yielded the following results optimum activity at pH 8 K, values phenylpyruvate, 1.2 X M phenylalanine, 13 X 10 Af -keto-j8-methylvalerate, 10 X 10 M isoleucine, 59 X 10 Af a-ketoisovalerate, 15 X 10 Af valine 111 X 10 Af oE-ketoglutarate, 24 X 10 M. Determination of the equilibrium constant for a-keto-/9-methylvalerate conversion to isoleucine with phenylalanine as amino group donor, yielded an average value of approximately 0.50. 

The enantioselective total synthesis of 1 commences with the formation of the enamine of morpholine and cyclohexane-1,2-dione (6), which actually exists almost entirely in the enolic form. Constant removal of water shifts the equilibrium to the side of the product. 2-Siloxyaniline 7, " which can be easily prepared from 2-aminophe-nol, reacts with the morpholine enamine in an acid-catalyzed transamination to give enamine 8. 

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