Disease relevance of ornithine

• Evolutionary drift of the argF and argl genes. Coding for isoenzyme forms of ornithine transcarbamylase in E. coli K12 [1].
• Gyrate atrophy of choroid and retina: deficient activity of ornithine ketoacid aminotransferase in cultured skin fibroblasts [2].
• Letter: Ornithine or citrulline therapy in treatment of Reye's syndrome [3].
• Mice lacking ornithine-delta-aminotransferase have paradoxical neonatal hypoornithinaemia and retinal degeneration [4].
• Increased ornithine decarboxylase activity in murine sarcoma virus infected cells [5].

Psychiatry related information on ornithine

• Ornithine aminotransferase in Huntington's disease [6].
• Compared to the reference sample group, higher glycine levels were found in each dementia subgroup; higher alanine, methionine and ornithine levels in MID, and SDAT; and higher phenylalanine levels in MID [7].
• The primary defect in patients presenting with a history of protein intolerance, mental retardation, and epilepsy of variable degree, with the unique triad of hyperornithinemia, hyperammonemia, and homocitrullinuria (the HHH syndrome) has been postulated to be a defect in translocation of ornithine into the mitochondria [8].

High impact information on ornithine

• ORNT1 expression restores ornithine metabolism in fibroblasts from patients with hyperammonaemia-hyperornithinaemia-homocitrullinuria (HHH) syndrome [9].
• Neurospora crassa ARG13 and Saccharomyces cerevisiae ARG11 encode mitochondrial carrier family (MCF) proteins that transport ornithine across the mitochondrial inner membrane [9].
• Gyrate atrophy of the choroid and retina is a disease characterized by progressive constriction of visual fields, a 10-fold to 20-fold elevation in plasma ornithine, and depressed activity of L-ornithine:2 oxoacid aminotransferase [10].
• Considerable genetic drift has occurred during the evolution of the two genes, argF and argl, which individually code for isoenzyme forms of ornithine transcarbamylase in E. coli K12 [1].
• The apparent Km of hepatic ornithine transcarbamylase for ornithine was in the normal range in patients with Reye's syndrome (mean 0.24 mM) [11].

Chemical compound and disease context of ornithine

• The polar domains of the two transcarbamoylases, aspartate transcarbamoylase (ATCase) and ornithine transcarbamoylase, (OTCase) from Escherichia coli bind the common substrate carbamoyl phosphate and share extensive amino-acid sequence homology [12].
• In a patient with gyrate atrophy of the choroid and retina, an arginine-deficient diet has reduced plasma ornithine concentration fivefold during the past 20 months [13].
• In the same condition, renal glycine and ornithine uptake took place; the more severe the acidosis, the greater was the renal extraction of these amino acids (P less than 0.001) [14].
• Serum ornithine carbamyl transferase activity was also raised in patients with Reye's syndrome, but levels were not increased after dialysis [15].
• Commonly used therapeutic strategies for hepatic encephalopathy aiming at the reduction of plasma ammonia levels such as protein restriction, oral neomycin, lactulose, or ornithine aspartate fail to improve the symptoms of hepatic myelopathy [16].

Biological context of ornithine

• The ornithine decarboxylase inhibitor DL-alpha-difluoromethyl ornithine inhibited a proliferation-associated increase in ornithine decarboxylase activity in cultured human promyelocytic leukemia cells, resulting in a marked suppression of cell proliferation and subsequent cell loss [17].
• Triggering of allostery in an enzyme by a point mutation: ornithine transcarbamoylase [18].
• The data suggest that the abnormal L-ornithine:2-oxoacid aminotransferase in the two patients studied has an altered binding site for ornithine [19].
• The phenotype of GA is characterized by progressive concentric reduction of the visual fields and ornithine accumulation [20].
• Phosphorylation of ornithine decarboxylase by a polyamine-dependent protein kinase [21].

Anatomical context of ornithine

• In the patients, the metabolic clearance of ornithine from the extracellular fluid was significantly delayed [22].
• We have reported that a single injection of 1 alpha,25-dihydroxyvitamin D3 into vitamin D-deficient chicks produces a marked increase of putrescine accumulation in the duodenum from two different sources, ornithine and spermidine [23].
• Import and processing of human ornithine transcarbamoylase precursor by mitochondria from Saccharomyces cerevisiae [24].
• Posttranslational uptake and processing of in vitro synthesized ornithine transcarbamoylase precursor by isolated rat liver mitochondria [25].
• The mitochondrial matrix enzyme ornithine transcarbamoylase (OTCase; ornithine carbamoyltransferase; carbamoylphosphate:L-ornithine carbamoyltransferase, EC 2.1.3.3) is encoded by a nuclear gene on the X chromosome, synthesized on cytoplasmic ribosomes, and translocated across both mitochondrial membranes [25].

Associations of ornithine with other chemical compounds

• The Km's for ornithine and carbamyl phosphate, pH optimum, and heat lability of ornithine transcarbamylase were normal [26].
• The ability of the compound to inhibit ornithine decarboxylase in vitro was demonstrated by the reduced amounts of putrescine synthesized from tritiated ornithine in Trypanosoma brucei suspensions [27].
• An inhibition of ornithine decarboxylase activity by difluoromethyl ornithine also augmented stress-induced ulcerogenesis and abolished the protective action of epidermal growth factor while the administration of spermine almost completely prevented stress ulcerations in rats both without and with pretreatment with difluoromethylornithine [28].
• The ability of the purified antizymes to inhibit the ornithine and arginine decarboxylases is stabilized in acidic buffers and is lost upon prolonged exposure to solutions at neutral or basic pH [29].
• Putative binding sites for the two substrates of the enzyme, carbamoyl phosphate and ornithine, are encoded by exons 3 and 9, respectively [30].

Gene context of ornithine

• Moreover, activation of p42/p44 and induction of p21(waf1/cip1) were prevented by exogenous putrescine but not ornithine, suggesting this effect was due to the inhibition of ODC by NO or DFMO [31].
• Importantly, arginase synthesizes ornithine, which is metabolized by the enzyme ornithine decarboxylase (ODC) to produce polyamines [32].
• In OTCase, mutations of putative ornithine binding residues, Asp-182, Asn-184, Asn-185, Cys-289, and Glu-256 greatly reduced the affinity for ornithine and impaired the interaction with arginase [33].
• Expression of either I(1,4,5)P3 6- or 3-kinase activity rescued growth of ipk2-deficient yeast at high temperatures, whereas only 6-kinase activity enabled growth on ornithine as the sole nitrogen source [34].
• The product of the bioA gene, 7,8-diaminopelargonic acid aminotransferase, was discovered to be related to ornithine aminotransferase [35].

Analytical, diagnostic and therapeutic context of ornithine

• Oral administration of alpha-difluoromethyl ornithine suppressed B16 melanoma development in mice 85 percent whereas interferon given subcutaneously inhibited tumor growth only 24 percent [36].
• Fetal liver biopsy for prenatal diagnosis of ornithine carbamyl transferase deficiency [37].
• Molecular cloning of human ornithine aminotransferase mRNA [38].
• To determine whether chronic, systemic reduction of ornithine can prevent this form of retinal degeneration, we used an arginine-restricted diet to maintain long term reduction of ornithine in a mouse model of OAT-deficiency (Oat(-/-)) produced by gene targeting [39].
• As early as 1 hour following reperfusion, circulating arginine levels decreased 10-fold and ornithine levels increased 4-fold [40].

References