Glutamate 5-phosphate, proline synthesis

We have already described the biosynthesis of glutamate and glutamine. Proline is a cyclized derivative of glutamate (Fig. 22-10). In the first step of proline synthesis, ATP reacts with the y-carboxyl group of glutamate to form an acyl phosphate, which is reduced by NADPH or NADH to glutamate y-semialdehyde. This intermediate undergoes rapid spontaneous cychzation and is then reduced further to yield proline. 

Enzymes catalyze almost every metabolic reaction in extant cells. A few tmusually facile reactions, such as cyclization of L-glutamate 7-semialdehyde to form pyrroline-5-carboxylate in the proline biosynthesis pathway and decarboxylation of 2-amino-3-oxo-4-phosphonooxybutyrate in the pyridoxal phosphate (PLP) synthesis pathway, do not require acceleration to satisfy the demands of the cell. For all other reactions, catalysis is required because the rates of nonenzymatic reactions are very slow. Modern enzymes are marvelous catalysts. They accelerate reactions by up to 20 orders of magnitude, prevent side reactions of reactive intermediates, and catalyze stereoselective and stereospecific reactions. Further, they are often exquisitely regulated by small molecule ligands. 

Fig. I. Metabolic map for synthesis and metabolism of glutamate and aspartate. AAT = aspartate aminotransferase AS = asparagine synthetase GAD = glutamic acid decarboxylase GDH = glutamate dehydrogenase GS = glutamine synthetase OAT = ornithine D-aminotransferase P5CDH = l-pyrroline-5-carboxylate dehydrogena.se PAG = phosphate-activated glutaminase PO = proline oxidase TCA = tricarboxylic acid.

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