Glutamate semialdehyde dehydrogenase

This enzyme [EC 1.2.1.41], also known as y-glutamyl-phosphate reductase and glutamate-5-semialdehyde dehydrogenase, catalyzes the reaction of L-glutamate 5-semialdehyde with orthophosphate and NADP+ to produce L-y-glutamyl 5-phosphate and NADPH. 

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.

Figure 12-4. Gamma-aminobutyric acid metabolic interactions. GA = glutaminase GABA = y-aminobutyric acid GABA-T = GABA a-oxaloglutarate transaminase GAD = glutamic acid decarboxylase GS = glutamic synthetase NAD+ = nicotinamide adenine dinucleotide PP = pyridoxal phosphate (vitamin B6) SSA = succinic semialdehyde SSADH = succinic semialdehyde dehydrogenase GHB = y-hydroxybutyric acid GBL = y-butyrolactone.

ALAcetylglutamic y-semialdehyde dehydrogenase N-Acetyl-L-glutamate y-semialde-hyde NADP oxidoreductase (phosphorylating)... 

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)... 

So, the biosynthesis of methionine (Met, M), the first of the essential amino adds to be considered (Scheme 12.13), begins by the conversion of aspartate (Asp, D) to aspartate semialdehyde in the same way glutamate (Glu, E) was converted to glutamate semialdehyde (vide supra. Scheme 12.6). Phosphorylation on the terminal carboxylate of aspartate (Asp, D) by ATP in the presence of aspartate kinase (EC 2.7.2.4) and subsequent reduction of the aspart-4 yl phosphate by NADPH in the presence of aspartate semialdehyde dehydrogenase (EC 1.2.1.11) yields the aspartate semialdehyde. The aspartate semialdehyde is further reduced to homoserine (homoserine oxoreductase, EC 1.1.1.3) and the latter is succinylated by succinyl-CoA with the liberation of coenzyme A (CoA-SH) in the presence of homoserine O-succinyl-transferase (EC 2.3.1.46). Then, reaction with cysteine (Cys, C) in the presence of cystathionine y-synthase (EC 2.5.1.48) produces cystathionine and succinate. In the presence of the pyridoxal phosphate protein cystathionine P-lyase (EC 4.4.1.8), both ammonia and pyruvate are lost from cystathionine and homocysteine is produced. Finally, methylation on sulfur to generate methionine (Met, M) occurs by the donation of the methyl from 5-methyltetrahydrofolate in the presence of methonine synthase (EC 2.1.1.13). 

Fig. 3.2. Diagnostic flow charts (a) GABA metabolism defects (b) hyperglycinemia and (c) fasting hyposerinemia. GT, GABA transaminase SSD, succinic semialdehyde dehydrogenase GAD, glutamic acid decarboxylase...

Proline. Prohne forms dehydroprohne, glutamate-y-semialdehyde, glutamate, and, ultimately, a-ketoglu-tarate (Figure 30—3, top). The metabohc block in type I kyperprolinemia is at proline dehydrogenase. 

---