Glutamate 1-semialdehyde aminotransferase

Figure 1-2 ALA synthesis by ALAS or the C5 pathway. The enzymes of the C5 pathway and their cofactors are as follows (a) glutamyl-tRNA reductase (requires Mg-ATP) (b) glutamyl-tRNA reductase (pyridoxal 5 -phosphate dependent and requires NAD(P)H) and (c) glutamate 1-semialdehyde aminotransferase.

THE GLUTAMATE 1-SEMIALDEHYDE AMINOTRANSFERASE OF BARLEY PURIFICATION OF THE PROTEIN, c-DNA CLONING, SEQUENCING AND CHARACTERISATION OF THE mRNA... 

The Glutamate 1-Semialdehyde Aminotransferase of Barley Purification of the Protein, c-DNA Qoning, Sequencing and Characterisation of the mRNA 585... 

Ornithine is an amino acid. However, it is not incorporated into proteins during the process of protein synthesis because no genetic codon exists for this amino acid. Although ornithine is normally regenerated by the urea cycle (one of the products of the arginase reaction), ornithine also can be synthesized de novo if needed. The reaction is an unusual transamination reaction catalyzed by ornithine aminotransferase under specific conditions in the intestine (Fig. 38.14). The usual direction of this reaction is the formation of glutamate semialdehyde, which is the first step of the degradation pathway for ornithine. 

Although it is widely held that glutamate semialdehyde is the substrate of the final step (with di-aminovalerate as a possible enzyme-bound intermediate), some authorities claim that 4,5-dioxo-valerate is an intermediate, and that this is converted into 5-aminolevulinate by 4,5-dioxovale-rate aminotransferase. The latter enzyme is present in plants and bacteria, but does not always display high activity. 

Figure 5. An example of a suicide substrate gabaculine and the postulated mechanism of inactivation of glutamate-l-semialdehyde aminotransferase.

Figure 1. Contribution of different pathways to the ornithine usedfor citrulline synthesis. De novo synthesis of ornithine Proline is oxidised by action of proline oxidase (1) to generate pyrrolidine-5-car boxy late (P5C). P5C interconverts spontaneously with glutamate semialdehyde (GSA). Glutamine is deamidated by action of glutaminase (2) and the resulting glutamate is converted into GSA by pyrrolidine-5-carboxylate synthase (3). GSA is used by ornithine aminotransferase (OAT 4) to generate ornithine. Note that OAT is usedfor both synthesis and disposal of ornithine. Preformed ornithine ornithine is generatedfrom the hydrolysis of arginine by arginase (5), or can be transported from plasma. Ornithine is used for citrulline synthesis by action of ornithine transcarbamylase (OTC 6).

Figure 6.3. GABA shunt as an alternative to a-ketoglutarate dehydrogenase in the citric acid cycle. 2-Oxoglutarate dehydrogenase, EC 1.2.4.2 glutamate decarboxylase, EC 4.1.1.15 GABA aminotransferase, EC 2.6.1.19 and succinic semialdehyde dehydrogenase, ECl.2.1.16.

The urea so formed is distributed throughout the body water and excreted. The renal clearance of urea is less than the glomerular filtration rate because of passive tubular back-diffusion. Diffusion of urea in the intestine leads to formation of ammonia, which enters the portal blood and is converted to urea in liver. Reentry of ornithine into mitochondria initiates the next revolution of the urea cycle. Ornithine can be converted to glutamate-y-semialdehyde (which is in equilibrium with its cyclic form A -pyrroline-5-carboxylate) by ornithine aminotransferase and de-carboxylated to putrescine by ornithine decarboxylase. Ornithine is also produced in the arginine-glycine trans-amidinase reaction. 

GABA-AT 7-aminobutyric acid aminotransferase GSA glutamate-1 -semialdehyde... 

Chlorophyll synthesis in plants is regulated at steps converting glutamate into S-aminolevulinate (ALA). The stromal protein glutamate 1-semialdehyde (GSA) aminotransferase catalyzes the last reaction in the synthesis of ALA. We identified and sequenced a c-DNA clone encoding the GSA-aminotransferase in order to study the expression of this enzyme and its catalytic mechanism of transamination. 

In plants, algae, cyanobacteria and some other bacterial species 5-aminolevulinate (ALA) is synthesized from glutamate (1-6). This reaction sequence involves ligation of glutamate to a tRNA species and subsequent reduction to glutamate-l-semialdehyde (GSA) (7). The conversion of GSA to ALA is then catalysed by GSA-aminotransferase (E.C. S.4.3.8.) (2,8). Dependent on the requirement of pyridoxamine-phosphate (PAMP) or pyridoxal-phosphate (PALP) for activity, either 4,5-diaminovalerate (8-10) or 4,5-dioxovalerate (DOVA) (5,11,12) are proposed as intermediates. 

I Homocitrate synthase 2 homocitrate dehydratase 3 homoaconitate hydratase 4 homoisocitrate dehydrogenase 5 2-aminoadipate aminotransferase 6 aminoadipate semialdehyde dehydrogenase 7 saccharopine dehydrogenase (L-glutamate forming) 8 saccharopine dehydrogenase (L-lysine forming)... 

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