7-Aminobutyric acid, transamination reactions

Aminobutyric acid (No. 1771) (y-aminobutyric acid) is endogenous, as it is formed from decarboxylation of the essential amino acid glutamic acid. It undergoes transamination with a-ketoglutaric acid to re-form glutamic acid and succinic semialdehyde. This semialdehyde is then converted to succinic acid in a reaction... 

An enzyme that transaminates y-aminobutyric acid has been shown to occur in brain and liver [IS, 14). The amino group acceptor is a-keto-glutaric acid and the reaction products are succinic semialdehyde and... 

Upon incubating rat liver extracts with DL-homoserine-2-C Matsuo et al. (74) demonstrated that the immediate reaction product was butyric acid. This compound was in part transaminated to a-aminobutyric acid and in part reduced to a-hydroxybutyric acid. Further d radation was accomplished by its decarboxylation to propionic acid. The complete oxidation then proceeds through conversion to succinic acid and the operation of the TCA cycle. 

Glutamic acid or glutamate is one of the most abundant AAs found in natural proteins (approximately 20%) and a major excitatory transmitter within the brain. It mediates fast synaptic transmission and is active in approximately one third of all central nervous system (CNS) synapses. It is also a precursor to gamma-aminobutyric acid (GABA), which is an inhibitory neurotransmitter important in brain metabolism. Glutamic acid readily participates in transamination reactions to produce other AAs and is converted to the TCA cycle intermediate a-ketoglutarate. The transport rate of glutamate from blood to brain in mature animals is much lower than that for neutral or basic AAs. ... 

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... 

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