Glutamic y-semialdehyde

L-glutamic-y-semialdehyde) B.flavum L-Glutamine pro sulfite is effective 13.2 144... 

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. 

Figure 30-3. Top Catabolism of proline. Numerals indicate sites of the metabolic defects in type I and type II hyper-prolinemias. Bottom Catabolism of arginine. Glutamate-y-semialdehyde forms a-ketoglutarate as shown above. , site of the metabolic defect in hyperargininemia.

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 praline 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 cyclization and is then reduced further to yield proline. 

Ornithine Glutamic-y- semialdehyde Putrescine Putrescine is toxic and has the odor of putrid flesh... 

Glutamine is hydrolyzed to glutamate and NH4 + by glutaminase. Proline and arginine are each converted into glutamate y-semialdehyde, which is then oxidized to glutamate (Figure 23.25). 

Glutamic y-semialdehyde cyclizes with a loss of H2O in a nonenzymatic process to give A i-pyrroline-5-carboxylate, which is reduced by NADPH to proline. Alternatively, the semialdehyde can be transaminated to ornithine, which is converted in several steps into arginine (Section 23.4.1). 

FIGURE 8.9 Arginine and proline catabolism. Glutamate-Y-semialdehyde, an intermediate in the pathways of arginine and proline breakdown, received its name because its structure consists of glutamate, but with the y-carboxyl group reduced to the aldehyde form. 

All of the amino acids except lysine, threonine, proline, and hydroxyproline participate in transamination reactions. Transaminases exist for histidine, serine, phenylalanine, and methionine, but the major pathways of their metabolism do not involve transamination. Transamination of an amino group not at the a-position can also occur. Thus, transfer of 3-amino group of ornithine to a-ketoglutarate converts ornithine to glutamate-y-semialdehyde. 

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. 

Proline. Proline catabolism begins with an oxidation reaction that produces A -pyrroline. The latter molecule is converted to glutamate-y-semialdehyde by a hydration reaction. Glutamate is then formed by another oxidation reaction. 

The transamination of P-aminoisobutyrate to form methylmalonate semialdehyde requires pyridoxal phosphate as a cofactor. This reaction is similar to the conversion of ornithine to glutamate y-semialdehyde. Then NAD+ serves as an electron acceptor for the oxidation of methylmalonate semialdehyde to methylmalonate. The conversion of methylmalonate to methylmalonyl CoA requires coenzyme A. The final reaction, in which methylmalonyl CoA is converted to succinyl CoA, is catalyzed by methylmalonyl CoA mutase, an enzyme that contains a derivative of vitamin B12 as its coenzyme. 

Glutamic acid acetylglutamic acid glutamic-y-semialdehyde —> acetylomithine... 

Proline A -pyiroline-5-carboxylate glutamate-y-semialdehyde glutamate... 

The final step in the conversion of proline to glutamate is the oxidation of pyrroline-5-carboxylate to glutamate. Since pyrroline-5-carboxylate is in equilibrium in solution with its straight chain form, glutamate-y-semialdehyde it is possible that the latter compound is the substrate for this last step. An enzyme A -pyrroline-5-carboxylate dehydrogenase (E.C. 1.5.1.12) has been found in mitochondrial preparations fixim several higher plant seedlings (Stewart and Lai, 1974) which will catalyze this reaction. 

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