Disease relevance of citrulline

• Resumption of arginine intake (or citrulline in the case of ornithine transcarbamylase deficiency) promptly led to correction of the hyperammonemia, hyperglutaminemia and hypoargininemia [1].
• L-arginine and L-citrulline increased production of NO and prevented salt-sensitive hypertension in Dahl/Rapp rats [2].
• Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients [3].
• Conclusions: In patients with short-bowel syndrome, postabsorptive plasma citrulline concentration is a marker of functional absorptive bowel length and, past the 2-year adaptive period, a powerful independent indicator allowing distinction of transient from permanent intestinal failure [4].
• Citrulline concentrations were significantly higher in rectal biopsy specimens from patients with active ulcerative colitis than in those from patients with quiescent disease or with normal histology [5].

Psychiatry related information on citrulline

• RESULTS: Plasma citrulline concentration was lower (P < 0.001) in patients with villous atrophy (24 +/- 13 micromol/L) than in healthy subjects (40 +/- 10 micromol/L) and patients with anorexia nervosa (39 +/- 9 micromol/L) [6].

High impact information on citrulline

• Here we describe a process, deimination, that converts histone arginine to citrulline and antagonizes arginine methylation [7].
• BACKGROUND: Ornithine transcarbamylase is an X-linked mitochondrial enzyme that catalyzes the synthesis of citrulline from carbamoyl phosphate and ornithine [8].
• The production of nitric oxide (NO), as measured by nitrite and citrulline production, was significantly higher in mTa-transformed endothelial cells in comparison with nontransformed control cells [9].
• The synthesis of NO (measured as citrulline and nitrate production) appeared to be very high in comparison with human endothelial cells; no citrulline and nitrate production was detectable in noninfected red blood cells [10].
• In transgenic lineages with three to eight transgene copies, bovine eNOS-specific mRNA, protein expression in the particulate fractions, and calcium-dependent NOS activity were confirmed by RNase protection assay, immunoblotting, and L-arginine/citrulline conversion [11].

Chemical compound and disease context of citrulline

• Wild-type mice preconditioned 24 h earlier with six cycles of 4-min coronary occlusion/4-min reperfusion exhibited a significant (P < 0.05) increase in myocardial iNOS protein content, iNOS activity (assessed as calcium-independent L-citrulline formation), and nitrite + nitrate tissue levels [12].
• Using two mouse models of HD, we demonstrate that the urea cycle deficiency characterized by hyperammonemia, high blood citrulline and suppression of urea cycle enzymes is a prominent feature of HD [13].
• The citrulline biosynthetic operon, argC-F, and a ribose transport operon, rbs, from Bacillus subtilis are negatively regulated by Spo0A [14].
• Mutants of E. coli K12 that overproduce ornithine transcarbamylase can be identified in Car- strains because they permit utilization of citrulline as a carbamyl phosphate source, due to reversal of the normal OTCase reaction; they are called Cut mutants (citrulline utilizers) [15].
• Renal uptake of glutamine and citrulline increased after ischemia reperfusion (SAL/I-R vs. SAL/C-L and ASE/I-R vs. ASE/C-L, both P < 0.01) [16].

Biological context of citrulline

• Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets [17].
• Furthermore, an antiproliferative action of NO was demonstrated by an inverse correlation between the amounts of nitrite or citrulline produced in response to different stimuli (LPS/IFN-gamma or LPS/IFN-gamma with growth factors) and the level of cellular proliferation [18].
• The coproduct of this signal-transduction pathway appeared to be L-citrulline [19].
• These observations indicate that ingestion of certain NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis [20].
• The biosynthesis of nitric oxide (NO) by the enzyme NO synthase (NOS) proceeds by the hydroxylation of L-arginine to form NG-hydroxy-L-arginine followed by the conversion of NG-hydroxy-L-arginine to L-citrulline and NO [21].

Anatomical context of citrulline

• In M phi and endothelial cells, citrulline and NO2-/NO3- are the stable endproducts of this metabolic pathway [22].
• Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease [6].
• The possibility of L-citrulline recycling in the maintenance of nitrergic neurotransmission in the opossum internal anal sphincter (IAS) smooth muscle strips was investigated [23].
• Plasma citrulline, a nonprotein amino acid produced by intestinal mucosa, is one candidate [4].
• L-citrulline recycling in opossum internal anal sphincter relaxation by nonadrenergic, noncholinergic nerve stimulation [23].

Associations of citrulline with other chemical compounds

• Production of labeled agmatine, citrulline, and ornithine from [3H]arginine was demonstrated and endogenous agmatine levels (10(-6)M) in plasma ultrafiltrate and kidney were measured by HPLC [24].
• Nitric oxide (NO), formed by conversion of arginine to citrulline and NO by NO synthase, mediates relaxation of vascular smooth muscle [25].
• Treatment with l-arginine or l-citrulline of eNOS-transfected cells partially inhibited, and combination of l-arginine and l-citrulline with antioxidants strongly prevented, high glucose-induced cellular senescence [26].
• Arg-depleted endothelial cells did not form urea or metabolize L-ornithine but converted L-citrulline (L-Cit) to L-Arg possibly via formation of L-argininosuccinic acid [27].
• We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue [28].

Gene context of citrulline

• Competitive inhibition studies, measurement of citrulline uptake, and lack of complementation in gap1- strains indicated that the human cDNA genes code for proteins that prevent GAP repression by ammonium [29].
• The conversion of L-arginine to L-citrulline, a relatively specific measure of NOS activity, was easily measured and inducible in fractionated HAECs, and > 90% of all L-arginine conversion was blocked by the NOS inhibitor, N omega-amino-L-arginine (L-NAA) [30].
• The peptide inhibited formation of L-citrulline by eNOS and nNOS with IC(50) values of 10.6 +/- 0.4 microM and 7.1 +/- 0.6 microM, respectively [31].
• A general amino acid permease cDNA (AAP2) was isolated from Arabidopsis by complementation of a yeast mutant defective in citrulline uptake [32].
• A greater increase on iNOS activity (fmol [3H] citrulline/min/microg protein) and a lesser increase in calcium/calmodulin-dependent NOS activity (cNOS) were observed in the obstructed renal medulla [33].

Analytical, diagnostic and therapeutic context of citrulline

• Using several citrulline-containing peptide variants in ELISA, antibodies could be detected in 76% of RA sera with a specificity of 96% [34].
• In patients with an autosomal recessive diamino acid transport disorder, lysinuric protein intolerance (LPI), we measured plasma and urinary amino acids basally, and during intravenous infusion of citrulline at two rates [35].
• To assess nNOS catalytic activity in intact animals we localized citrulline, which is formed stoichiometrically with NO, by immunohistochemistry. nNOS beta is prominent in several brain regions of wild-type animals and shows 2-to 3-fold up-regulation in the cortex and striatum of nNOS(delta/delta) animals [36].
• They also suggest that amniotic fluid citrulline concentrations provide strong adjunctive evidence for this prenatal diagnosis [37].
• Argininosuccinate synthetase expression was selected for in citrulline-containing medium, and the human origin of the argininosuccinate synthetase expressed by seven transferents was identified by isoelectric focusing [38].

References