A’-Pyrroline -carboxylate

Maleylacetoacetate Fumarylacetoacetate Acetoacetate ( Glutamate 4-semialdehyde A -Pyrroline-5-carboxylate... 

One route of catabolism of proline is essentially the reverse of its formation from glutamate. Proline oxidase yields A -pyrroline 5-carboxylate.145a,b... 

However, following its formation, the semialdehyde undergoes a spontaneous cyclization and is converted to a A -pyrroline-5-carboxylic acid (P5C), a proline precursor. 

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. 

Metabolism of proline (1) A -pyrroline-5-carboxylate (P5C) synthase (2) ornithine aminotransferase (3) P5C reductase (4) proline oxidase (5) P5C dehydrogenase (6) ornithine decarboxylase. 

FIG. 5.1 Proline metabolism. 1, Proline oxidase 2, A -pyrroline-5-carboxylate reductase 3, spontaneous reaction 4, A -pyrroline-5-carboxylate dehydrogenase 5, glutamate dehydrogenase 6, see Fig. 5.2. 

Glutamyl-5-semialdehyde - A -pyrroline-5-carboxylic acid + HjO L-Proline NADCP)" 5-oxidoreductase (E.C. 1.5.1.2)... 

Fig. 3. Proline and arginine synthesis and degradation to show interrelationships between the pathways. The structures are glutamic acid (GLU), ornithine (ORN), citrulline (CIT), arginine (ARG), urea. 2-oxo-5-amino valeric acid (OAV), A -pyrroline-2-carboxylic acid (P2C), proline (PRO), A -pyrroline-5-carboxylic acid (P5C), glutamic semialdehyde (GSA).

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. 

Incorporation of D,L-[5- C]A -pyrroline-5-carboxylic acid into Nicotine in Nicotiana rustica... 

The use of an amine donor, which forms an unstable keto coproduct. For instance, cysteinesulfinic acid was used in transamination to furnish the p-sulfinic acid analog of pyruvate, which spontaneously decomposes into SO2 and pymvate [1732]. In a related fashion, a,co-diamino acids, such as ornithine or leucine yield amino-ketoacids, which (nonenzymatically) cyclize to the corresponding A -pyrroline-5-carboxylate and A -piperidine-2-carboxylate, respectively, as dead-end products [1733, 1734],... 

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