The expression of the short isoform, regulated by ornithine, is prominent in the gut, where it directs P5C towards arginine biosynthesis. The long isoform, which is insensitive to ornithine, is ubiquitously expressed and mediates proline biosynthesis. The two amino acid insertion in the long isoform abolishes the feedback inhibition of P5CS activity by ornithine. In fact, when these two amino acids are inserted into the E. coli GK, proline inhibition diminishes by around 150-fold. Additionally, the insertion interferes with glutamate binding, thus confirming its key regulatory role (unpublished results from our laboratory). This finding suggests that the location of the catalytic site and structural organization of the inhibitory mechanism of human P5CS are similar to what has been described for bacterial GKs and plant P5CSs.
While the primary precursor for proline biosynthesis in some plants is glutamate, ornithine serves this function in others. Nevertheless, under conditions of osmotic stress, all plants predominantly use glutamate as a substrate.,, In plants, proline is useful not only during conditions of drought and high salt osmotic stress, but also as a response to environmental changes such as low temperature, nutritional deficits, heavy metals, UV radiation, and bacterial pathogens. In some species, proline also accumulates during normal development in flowers, pollen, ovules, or fruits. Depending on the plant species, proline accumulation results from different combined strategies that may include any of the following changes: an increase of the P5CS transcription level, and/or an increase of P5CS activity, and/or the inhibition of proline degradation which is reduced in plants under water stress.,, In fact, high salt concentrations inhibit the activity of proline dehydrogenase (PRODH). In response to other situations, proline storage is produced by decreased pyrroline-5-carboxylate dehydrogenase (P5CDH) activity. Paradoxically, an external supply of proline has proved toxic for plants as it causes cell death induced by P5C accumulation, with an accompanying increase of ROS production.
Proline Precursors to Sustain Mammalian Collagen …
A study conducted in yeast revealed that either specific mutations or the disruption of GPR permitted the growth of a glutathione auxotroph strain. This was apparently achieved through the accumulation of γ-glutamyl phosphate which contributed to the production of small amounts of glutathione, thus linking the proline biosynthetic pathway with tolerance to oxidative stress.
Proline biosynthesis: multiple defects in Chinese hamster ovary cells
The human P5CS gene, known as ALDH18A1 (the member 18A1 of the aldehyde dehydrogenase family), is located on chromosome 10, spans about 50 kb and comprises 18 exons. The transcript has a length of 3462 bp, encodes a protein of 795 amino acids, and has a molecular weight of 87.3 kDa. The 64 N-terminal residues present characteristic features of a mitochondrial targeting sequence with two potential cleavage sites. The P5CS gene undergoes alternative splicing to generate two isoforms which are differentially expressed and differ only by the insertion/deletion of two amino acids at the GK moiety.
Amino Acid Bio Synthesis | Biosynthesis | Alanine
N2 - There are two forms of arginase in humans, both catalyzing the hydrolysis of arginine to ornithine and urea. Recent studies in animal models and in Type I arginase-deficient patients suggest that Type II arginase is inducible and may play an important role in the regulation of extra-urea cycle arginine metabolism by modulating cellular arginine concentrations. We PCR amplified and cloned the human Type II arginase gene, the first nonliver arginase gene reported in mammals. While sequence homology to Type I arginase, arginase activity data, and immunoprecipitation with an anti-AII antibody confirm the identity of this gene. Northern blot analysis demonstrates its differential expression in the brain, prostate, and kidney. Type II arginase may be an important part of the arginine regulatory system affecting nitric oxide synthase, arginine decarboxylase, kyotorphin synthase, and arginine-glycine transaminase activities and polyamine and proline biosynthesis.
animals and microorganisms In mammals & plants, ..
In addition, a crystal structure corresponding to the human GPR moiety has been solved (PDB ID 2H5G). It shares the common architecture of the other solved GPRs, with three independent domains and a hinge region between domains II and III [Fig. (D,F)]. Based on structure and sequence comparisons, the catalytic cysteine can be identified as Cys612. As with other mammalian enzymes, human GPR moiety contains an extra tail of around 20–35 amino acids which surrounds the oligomerization domain [Fig. (F)]. The crystal structure reveals that the human GPR moiety is organized as a dimer with the oligomerization domain from one subunit interacting with the extended region of the hinge between domains II and III of the other monomer. As a result, the oligomerization domains are on one side, and domains I and II from both monomers are located on the other side.