Disease relevance of PYCR1

• In samples of colonic adenocarcinomas, the mean activities of thymidine kinase, glucose-6-phosphate dehydrogenase, phosphoserine phosphatase and pyrroline-5-carboxylate reductase were several fold higher than those of nonneoplastic colon [1].
• The primary structure of pea P5CR is 85% identical with that of soybean and exhibits significant homology to human, yeast, and Escherichia coli P5CR [2].
• The variation among subjects in the degree of plasma P5C fluctuation could not be explained by differences in total protein and caloric intake or body weight [3].
• We have determined the first crystal structure of P5CR from two human pathogens, Neisseria meningitides and Streptococcus pyogenes, at 2.0 angstroms and 2.15 angstroms resolution, respectively [4].
• The enzymatic cycle between P5C and proline is very important in many physiological and pathological processes [5].

High impact information on PYCR1

• Pyrroline-5-carboxylate reductase, which converts pyrroline-5-carboxylate to proline, has been identified in human erythrocytes [6].
• Pyrroline-5-carboxylate reductase in human erythrocytes [6].
• We examined the kinetic properties of erythrocyte pyrroline-5-carboxylate reductase and compared them to the properties of the enzyme from proliferating cultured human fibroblasts [6].
• The results directly implicate proline oxidase and the proline/P5C pathway in p53-induced growth suppression and apoptosis [7].
• In addition to previously described genes such as hepsin, overexpression of several genes was found that has not drawn attention before, such as the genes encoding the specific granule protein (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)-phospholipase A2, and the anti-apoptotic gene PYCR1 [8].

Chemical compound and disease context of PYCR1

• Proline analogues such as L-THFA and DL-P5C also stimulate PutA binding to E. coli polar lipid vesicles with K(D) values ranging from approximately 3.6 to 34 nM (pH 7.4) for the PutA-lipid complex [9].
• We now report a method for measuring pyrroline-5-carboxylate made possible by a preparation of purified Escherichia coli pyrroline-5-carboxylate reductase [10].

Biological context of PYCR1

• Pyrroline-5-carboxylate (P5C), a proline-derived metabolite generated by proline oxidase, inhibited the proliferation and survival of ECV-304 and DECV cells and induced apoptosis in both cell lines [7].
• 4. The kinetics characteristics of P5C uptake included an apparent Km of 0.46 +/- 0.04 mM and a Vmax of 19.6 +/- 1.8 nmol/min/mg [11].
• Genomic analysis suggested that two to three copies of the P5CR gene are present per haploid genome in pea [2].
• DNA sequence analysis of one full-length 1.3-kb clone (pPPS3) indicated that the pea P5CR gene contains a single major open reading frame encoding a polypeptide of 28,242 Da [2].
• Comparison of the native structure of P5CR to structures complexed with L-proline and NADP+ in two quite different primary sequence backgrounds provides unique information about key functional features: the active site and the catalytic mechanism [4].

Anatomical context of PYCR1

• We suggest that, in some cell types including human erythrocytes, a physiologic function of pyrroline-5-carboxylate reductase is the generation of NADP+ [12].
• The 1810-base pair pyrroline-5-carboxylate reductase cDNA hybridizes to a 1.85-kilobase mRNA in samples from human cell lines and predicts a 319-amino acid, 33.4-kDa protein [13].
• The oxidation of proline to glutamate in mitochondria requires two enzymes, proline oxidase and pyrroline 5-carboxylate (P5C) dehydrogenase [14].
• P5C reductase and proline oxidase in the larva of the blowfly, Aldrichina grahami, were found to be localized mainly in the fat body mitochondrial matrix and the muscle, respectively [15].
• Intermediates of Gln interconversion: glutamate (Glu) and pyrroline-5-carboxylate (P5C) stimulate collagen biosynthesis in cultured cells but evoke different maxima of collagen biosynthesis stimulating activity at different times of incubation [16].

Associations of PYCR1 with chemical compounds

• We cloned a human pyrroline-5-carboxylate reductase cDNA by complementation of proline auxotrophy in a Saccharomyces cerevisiae mutant strain, DT1100 [13].
• Pyrroline-5-carboxylate reductase (EC 1.5.1.2) catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline [13].
• Erythrocyte pyrroline-5-carboxylate reductase is competitively inhibited by NADP+ [12].
• Purified human erythrocyte pyrroline-5-carboxylate reductase. Preferential oxidation of NADPH [12].
• These studies have established that if the reverse reaction occurs the rate is 1/15,000th of the rate at which P5C is oxidized to glutamate [14].

Other interactions of PYCR1

• Tissues from an earthworm, a starfish and a sea-squirt have been found to contain the enzymes arginase, ornithine aminotransferase and pyrroline-5-carboxylate reductase which are necessary to convert arginine to proline [17].

Analytical, diagnostic and therapeutic context of PYCR1

• Cloning human pyrroline-5-carboxylate reductase cDNA by complementation in Saccharomyces cerevisiae [13].
• Using site-directed mutagenesis, two cysteine residues were introduced in close spatial proximity (P5C/A135C) [18].
• Purification, characterization, and crystallization of human pyrroline-5-carboxylate reductase [5].

References