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Results for “Citrulline”

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At least 19 recordsLinked to original sources

PubMed2026

Distinct HLA Associations for Antibody Multireactivity With Citrulline-Containing Type II Collagen Epitopes Versus More Limited Antibody Reactivity With Citrulline-Containing IgG Epitopes in Rheumatoid Arthritis.

OBJECTIVE: Anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) can be promiscuous, with cross-reactive binding to many antigens containing short motifs, or private with little cross-reactivity. Also, ACPA reactivity patterns differ among patients with RA, including for motif-containing epitopes in important self-antigens like collagen and IgG (bound by RA-associated rheumatoid factors [RFs]), with limited understanding of the underlying mechanism. The objective of this study was to determine if HLA alleles associate with ACPA reactivity patterns. METHODS: For 100 ACPA+RF+ participants with RA, serum IgG binding was quantified by enzyme-linked immunosorbent assay to 10 citrulline-containing peptides derived from Type II collagen and IgG1 (nine with motifs), and HLA loci were genotyped. Also, antibody and serum multireactivity were evaluated. HLA alleles present differentially in RA participants with high versus low IgG binding to specific peptides, as well as with multireactivity versus limited reactivity were identified by Fisher's exact test. RESULTS: Serum IgG multireactivity for citrulline-glycine motif-containing collagen peptides was high, at least partially due to promiscuous antibodies. HLA-DQA1*01:02 was present in more participants with anticitrullinated collagen antibodies and multireactive sera. In contrast, serum multireactivity was low for IgG1-derived peptides due at least in part to more private antibodies. Shared epitope-containing HLA-DRB1*04:01 was present more frequently in participants with RA-associated RFs irrespective of the citrulline-serine motif and less frequently in participants with anticitrullinated collagen antibodies. Several HLA alleles associated with specific antibody reactivities. CONCLUSION: Different HLA alleles may contribute to the different reactivity patterns of promiscuous anticitrullinated collagen antibodies and more private RA-associated RFs.

Humans↗

PubMedDate not supplied

Origin of the ammonia used for mitochondrial citrulline synthesis as revealed by 13C-15N spin coupling patterns observed by 13C NMR.

The sources of ammonia used by isolated, intact rat liver mitochondria in the production of citrulline have been investigated in situ using a novel methodology based on the analysis of 13C-15N heteronuclear couplings observed by 13C NMR. Isolated mitochondria from rat liver were incubated with ornithine, 13CO3H- and 15NH4Cl, using unlabeled glutamate or glutamine as alternative, intramitochondrial nitrogen donors. The production of (7-13C, 8-15N) or (7-13C, 8-14N) citrulline was determined in situ by 13C NMR and the relative proportions of 15N- and 14N-citrullines confirmed by high resolution 13C NMR analysis of the C-7 citrulline resonance observed in perchloric acid extracts prepared at the end of the incubations. The 15N fractional enrichment of the intramitochondrial NH3 pool was manipulated either by modifying the 15N enrichment of added 15NH4Cl, or by altering the concentration of the unlabeled nitrogen donors in the incubation medium. Fractional 15N enrichments measured in the N-8 nitrogen of the resulting (7-13C) citrulline closely paralleled those of the external 15NH4Cl with minor dilutions derived from the unlabeled nitrogen contribution from the alternative substrates. In the presence of 10 mM 15NH4Cl, 10 mM glutamate contributed 4% of the citrulline N-8 nitrogen. Under similar conditions, the contribution of nitrogen from 10 mM glutamine to N-8 citrulline was 6%. These results indicate that the primary source of ammonia used for citrulline synthesis by isolated, intact rat liver mitochondria is extramitochondrial, providing also an illustration of the use of 13C-15N spin coupling patterns observed by 13C NMR, as a new tool in the study of ammonia metabolism.

Ammonia↗

PubMed1975

Citrulline metabolism in normal and citrullinemic human lymphocyte lines.

Citrullinemia is one of the five aminoacidurias associated with the Krebs-Henseleit urea cycle. A long-term lymphocyte line (UM-21) derived from a patient with this disease and nine of ten clones of this line were found to have no activity for the enzyme argininosuccinate synthetase (AS), as demonstrated by their inability to grow in medium in which citrulline had been substituted for arginine, by their inability to incorporate arginine-C14 derived from citrulline-C14 into cellular protein, and by direct enzyme assay. One clone had normal or nearly normal argininosuccinate synthetase activity, as demonstrated by the same criteria. Nutritional "variants" able to grow logarithmically in medium containing citrulline were isolated from UM-21 and three clones. The apparent Kms of AS for citrulline in UM-21, the ten clones, the variant lines, and a normal line were measured and fell into three groups: AS in UM-21 and nine clones had no measurable apparent Km for citrulline; AS in the variant cells had apparent Kms for citrulline of approximately 20 mM; and AS in the normal cell line and one clone had apparent Kms for citrulline of 0.2 mM. The data suggest that the defect in the citrullinemic cell lines is due to a mutation in the structural gene coding for argininosuccinate synthetase.

Amino Acid Metabolism, Inborn Errors↗

PubMed1992

Nitric oxide synthase from cerebellum catalyzes the formation of equimolar quantities of nitric oxide and citrulline from L-arginine.

This study examined whether constitutive nitric oxide (NO) synthase from rat cerebellum catalyzes the formation of equimolar amounts of NO plus citrulline from L-arginine under various conditions. Citrulline was determined by monitoring the formation of 3H-citrulline from 3H-L-arginine. NO was determined by monitoring the formation of total NOx (NO+nitrite [NO2-] + nitrate [NO3-]) by chemiluminescence after reduction of NOx to NO by acidic vanadium (III). Equal quantities of NO plus citrulline were generated from L-arginine and the formation of both products was linear for about 20 min at 37 degrees C provided L-arginine was present in excess to maintain a zero order reaction rate. Deletion of NADPH, addition of the calmodulin antagonist calmidazolium, or addition of NO synthase inhibitors (NG-methyl-L-arginine, NG-amino-L-arginine) abolished or markedly inhibited the formation of both NO and citrulline. The Km for L-arginine (14 microM; 18 microM) and the Vmax of the reaction (0.74 nmol/min/mg protein; 0.67 nmol/min/mg protein) were the same whether NO or citrulline formation, respectively, was monitored. These observations indicate clearly that NO and citrulline are formed in equimolar quantities from L-arginine by the constitutive isoform of NO synthase from rat cerebellum.

Amino Acid Oxidoreductases↗

PubMed1976

Effect of pent-4-enoic acid, propionic acid and other short-chain fatty acids on citrulline synthesis in rat liver mitochondria.

19 The effect of pent-4-enoic acid, propionic acid and several other short-chain fatty acids on citrulline synthesis in rat liver mitochondria was studied. 2.Pent-4-enoate at 1 mM inhibited mitochondrial citulline synthesis by about 80-90%. It is concluded that pent-4-enoate inhibits citrulline synthesis by interfering with some aspect of mitochondrial energy metabolism. This results in impairment of mitochondrial ornithine uptake or depletion of mitochondrial ATP, which, in turn, impairs carbamoyl phosphate synthesis or both. Evidence in support of this conclusion includes: pent-4-enoate has no effect on citrulline synthesis supported by succinate or exogenous ATP; pent-4-enoate lowers the medium plus mitochondrial ATP concentration; finally, when glutamate is the oxidizable substrate, pent-4-enoate decreases the carbamoyl phosphate concentration in mitochondria incubated without ornithine to minimize citrulline synthesis and impairs the mitochondrial uptake of ornithine, but it has neither effect when succinate is the oxidizable substrate. 4. Propionate, butyrate and crotonate also inhibit mitochondrial citrulline synthesis, but much less than pent-4-enoate. 5. Acetate, pentanoate, pent-2-enoate, hexanoate, octanoate, isovalerate, tiglylate and alpha-methylbutyrate have little or no effect on mitochondrial citrulline synthesis.

Adenosine Triphosphate↗

PubMed1979

The presence of citrulline in epidermal proteins.

Citrulline is present in the stratum corneum proteins of human, cow snout, pig snout and guinea pig epidermis but is absent from the stratum corneum proteins of frog, mouse, turtle, rat and hamster epidermis. The amino acid is released by acid hydrolysis and ranges from 1.7 to 5.5 residues per thousand residues of protein amino acid. Protein derived citrulline co-chromatographs with authentic L-citrulline on an amino acid analyzer, on Dowex-50, on Dowex-2 and on thin-layer chromatography. Dansylated material co-chromatographed with authentic dansyl-L-citrulline in two thin-layer chromatography systems. Labelling experiments have shown that the protein bound citrulline is derived from protein bound arginine and probably results from enzymatic conversion of the guanido group to the ureido group.

Animals↗

PubMed1979

Selective growth of some rodent epithelial cells in a medium containing citrulline.

We have defined a medium (called Sun's modified Waymouth medium) that selectively cultures some rodent epithelial cells that are capable of using citrulline in place of arginine. A growth-response study of the ability of 47 different mammalian cell cultures (of mouse, rat, Syrian hamster, Chinese hamster, guinea pig, rabbit, monkey, and human origin) to use arginine or its biosynthetic precursors, ornithine, citrulline, or argininosuccinate, showed that all epithelial cells and some fibroblasts are capable of growing in citrulline medium; however, primary embryo fibroblasts and 12 established fibroblast cell lines derived from Syrian hamsters failed to grow. The citrulline medium also allowed selective outgrowth of epithelial cells, without contaminating fibroblasts, from Syrian hamster tracheal explants. This absolute nutritional difference between Syrian hamster epithelial and fibroblast cells allows citrulline medium to be used for selective cultivation of epithelial cells, which should be valuable for study of growth, differentiation, and malignant transformation of mammalian epithelial cells.

Animals↗

PubMed1992

Characteristics of L-citrulline transport across rat small intestine in vitro.

The amino acid L-citrulline is an important intermediate of urea cycle and a key precursor for arginine biosynthesis. We have examined the characteristics of citrulline transport across the everted sacs of the rat small intestine. Our studies suggest that the optimal site of citrulline absorption is middle to lower ileum. It shows active transport, and this transport is predominantly Na+ dependent. Its uptake is significantly inhibited by ouabain, dinitrophenol, sodium azide, and sodium cyanide. Kinetic estimation reveal an apparent substrate concentration at 1/2 maximum velocity of 4.10 +/- 0.86 mM and a Vmax of 18.7 +/- 1.66 mumol/g wet weight tissue/30 min. Analog inhibition studies suggest that citrulline may share the neutral brush border system described for the mucosal brush border membranes of the rabbit jejunum or a system analogous to system ASC described for nonepithelial cells and for basolateral membranes of certain epithelia. In conclusion, the rat small intestine has developed a specific carrier-mediated, Na(+)-dependent pathway for citrulline absorption.

Amino Acids↗

PubMed1975

Hyperdibasicaminoaciduria, hyperammonemia, and growth retardation: Treatment with arginine, lysine, and citrulline.

A 9-year-old girl with hereditary dibasicaminoaciduria has been studied for three years. Initially, clinical features were: growth failure; anorexia and aversion to protein, spontaneous daily protein intake averaging only 10 gm; fasting and postprandial venous hyperammonemia; subnormal plasma concentrations of lysine, arginine, ornithine, and citrulline, with generalized hypermonobasicaminoacidemia; abnormally high renal clearances of lysine, arginine, and ornithine; and intestinal malabsorption of lysine and arginine. Intestinal absorption of citrulline, a precursor of arginine and ornithine, was normal. The patient was observed during four sequential 6-month periods as follows: no treatment (Period I); dietary supplement of arginine and lysine (Period II); dietary supplement of citrulline and lysine (Period III); no treatment (Period IV). During Periods II and III growth rate increased 3- to 4-fold, spontaneous protein intake increased 2- to 3-fold, and abnormalities in blood NH3 and the plasma aminogram were partially corrected. In most respects the citrulline plus lysine supplement was more beneficial than that of arginine plus lysine.

Amino Acid Metabolism, Inborn Errors↗

PubMed1979

The stimulation of the mitochondrial respiration by citrulline synthesis.

1. The influence of ammonia and ornithine on the oxygen uptake and the formation of citrulline was investigated with isolated rat liver mitochondria. The experiments were performed in a cytosol-like saline medium at 38 degrees C. 2. Under these conditions an increase of the respiration rate by ammonia and ornithine was observed, but a small response to external ADP, only. The missing stimulation by ADP was due to a partial inhibition of the respiratory chain by traces of zinc (approximately 1 microM) present in the medium. This inhibition was only detected at low concentrations of mitochondria. 3. For activation of respiration by ammonia plus ornithine two different processes were responsible: (i) chelation of the inhibiting zinc by ornithine, which could be prevented by EDTA; (ii) ADP production in the matrix space during formation of carbamoyl phosphate, which could be prevented by oligomycin but not by carboxyatractyloside. 4. This stimulus of the carbamoyl phosphate formation and of the equivalent citrulline synthesis on the mitochondrial respiration ran to 12% of that increase caused by phosphorylation of external ADP. The maximum rate of citrulline formation was limited by the activity of carbamoyl phosphate synthetase. 5. Added ADP suppresses the production of citrulline probably by the exchange of extramitochondrial ADP versus intramitochondrial ATP. The data suggest a common adenine nucleotide pool delivering ATP to the adenine nucleotide translocase as well as to the carbamoyl phosphate synthetase.

Animals↗

PubMed1977

The enzymic derivation of citrulline residues from arginine residues in situ during the biosynthesis of hair proteins that are cross-linked by isopeptide bonds.

An enzymic activity present in hair follicles is described that can convert arginine residues to citrulline residues in proteins in situ. The Ca2+ dependent enzyme activity has been detected in hair follicle extracts but not in similar extracts of serum, liver or brain. The enzyme appears to act on proteins other than hair proteins and the citrulline produced can be quantitated in acid hydrolysates by a colorimetric procedure. The formation of citrulline has been confirmed by amino acid analysis and does not appear to be related to the formation of isopeptide linkages which is catalysed by the transamidase present in hair follicles.

Amino Acids↗

PubMed1977

The origin of citrulline-containing proteins in the hair follicle and the chemical nature of trichohyalin, an intracellular precursor.

The present studies have demonstrated that the medulla and inner root sheath cells develop within their cytoplasm a protein that is unique in composition and is present in the trichohyalin granules. The protein is rich in arginine residues, some of which undergo a side-chain conversion in situ into citrulline residues. An unusual Ca2+-dependent enzyme activity distinguishable from cross-linking transamidase has been detected in the hair follicle and will act in vitro on trichohyalin protein as the natural substrate. The conversion in vivo must occur during the time that the medullary and inner root sheath cells move up the follicle and their cytoplasm fills with cross-linked protein containing citrulline. The function of citrulline in these proteins is not understood but its formation is a major process during hair growth.

Amino Acids↗

PubMed1992

Clinical test of renal guanidinoacetic acid metabolism by oral citrulline and creatine loading.

We devised a clinical test of renal metabolism based on the synthesis of guanidinoacetic acid from citrulline in the proximal convoluted tubule. Intravenous administration of a citrulline/creatine solution to rats with modified levels of renal glycine amidinotransferase activity revealed a strong correlation (r = 0.921) between this activity and urinary guanidinoacetic acid excretion. Citrulline (1.75 g) and creatine (1.50 g) were administered orally to healthy individuals and patients with chronic glomerulonephritis. In the healthy individuals, urinary guanidinoacetic acid excretion increased 5-fold by 2 h after dosing (15.1 +/- 2.2 vs. 2.8 +/- 1.1 mg/h). In the glomerulonephritis patients, blood clearance of citrulline decreased as the creatinine clearance decreased and urinary guanidinoacetic acid excretion also decreased. Of 56 patients with glomerulonephritis or diabetes mellitus, one had increased urinary guanidinoacetic acid excretion associated with an excess of adrenal androgens. This test appears a useful, noninvasive and simple method for examining the metabolic activity of the renal proximal convoluted tubules.

17-Ketosteroids↗

PubMed1992

Biosynthesis of nitric oxide and citrulline from L-arginine by constitutive nitric oxide synthase present in rabbit corpus cavernosum.

The objective of this study was to determine whether a constitutive isoform of nitric oxide (NO) synthase is present in rabbit corpus cavernosum that could account for the involvement of the L-arginine-NO pathway in neurogenically-elicited relaxation of the corpus cavernosum and, therefore, penile erection. Citrulline was determined by monitoring the formation of 3H-citrulline from 3H-L-arginine. NO was determined by monitoring the formation of total NO(x) (NO+nitrite [NO2-]+nitrate [NO3-]) by chemiluminescence after reduction of NO(x) to NO by acidic vanadium (III). Equimolar quantities of NO plus citrulline were generated from L-arginine and the formation of both products was time-dependent at 37 degrees C. NO synthase activity was distributed almost entirely to the cytosolic fraction. Enzymatic activity was completely dependent on NADPH, calmodulin, and calcium. Addition of tetrahydrobiopterin increased NO synthase activity by about 30 percent. The NO synthase inhibitor NG-nitro-L-arginine, abolished enzymatic activity. The Km for L-arginine was 17 microM and the Vmax of the reaction was 18 pmol/min/mg protein. These observations indicate that a cytosolic, constitutive isoform of NO synthase, like that found in brain neuronal tissue, is present in rabbit corpus cavernosum.

Amino Acid Oxidoreductases↗

PubMed1976

Isolation of peptides containing citrulline and the cross-link, epsilon-(gamma-glutamyl)lysine, from hair medulla protein.

The epsilon-(gamma-glutamyl)lysine cross-link has been unequivocally localized in the citrulline-containing protein of hair medulla tissue. This was achieved by the isolation of cross-linked peptides that contain citrulline. The peptides were purified by molecular sieving, cation-exchange and paper chromatography and paper electrophoresis and their amino acid compositions are reported. They were detected by analyzing a large number obtained from a tryptic digest of thermolytic peptides of the medulla protein. There is no evidence at present as to whether the cross-link is in fact inter- or intrachain, or both.

Amino Acids↗

PubMed1990

Immobilization and treatment of Streptococcus faecalis for the continuous conversion of arginine into citrulline.

Citrulline is one of the steps of the arginine dihydrolase system of Streptococcus faecalis. We have shown that the bacteria, immobilized in polyacrylamide gel and treated with Cetyl trimethyl ammonium bromide (CTAB) or heat, were able to convert arginine to citrulline. Used continuously in a column reactor, the entrapped cells have a stable enzymatic activity for at least 30 days at 45 degrees C.

Arginine↗

PubMed1979

The utilization of ornithine and citrulline by the growing kitten.

Previous experiments have demonstrated that cats fed an arginine free purified amino acid diet (-Arg) could be protected from hyperammonemia by the inclusion of ornithine in the diet. Experiments reported here show that diets containing ornithine added at an equimolar (+Orn) or five times equimolar (+5 Orn) to replace arginine in the +Arg basal diet (2.0% Arg . HCl), were incapable of maintenance of body weight. Growing kittens fed a -Arg +Orn and -Arg +5 Orn diets had a daily rate of body weight loss of 6.5 +/- 0.6 and 7.9 +/- 2.2 g, respectively, which is somewhat less than the mean rate of weight loss of kittens fed diets devoid of most of the other amino acids indispensable for the kitten. When citrulline was added to a -Arg diet at an equimolar level to the arginine in the +Arg basal diet, growth rates were equivalent. The mean plasma free ornithine concentration of kittens receiving the -Arg +5 Orn diet was about 33 times higher than when they were fed the +Arg diet. For kittens fed the -Arg + Orn and -Arg +5 Orn diets the mean plasma free arginine was less (but significant only for the -Arg + Orn diet) than that observed for the basal diet. When the -Arg + Cit diet was fed, plasma free arginine concentration was similar and plasma free citrulline was about 18 times higher than when these cats were fed the basal diet.

Amino Acids, Essential↗

PubMed1977

Increase in arginine and citrulline production by 6-azauracil-resistant mutants of Bacillus subtilis.

In the arginine producer AHr-5, an L-arginine hydroxamate-resistant mutant of Bacillus subtilis, accumulation of N8-acetyl-L-ornithine increased as the level of L-arginine accumulation increased in the medium containing L-glutamic acid. Ornithine carbamoyltransferase of this strain was genetically derepressed. These results suggested that carbamoylphosphate might be deficient in vivo. With the intention to increase endogenous carbamoylphosphate, pyrimidine analogs inhibiting growth were selected and the mutants resistant to these compounds were derived from the AHr-5 mutant. Of the resistant mutants derived, the 6-azauracil-resistant mutant AAr-9 produced 28 mg of L-arginine per ml, which corresponded to more than twofold the amount produced by the parent strain. Derivation of an arginine-requiring mutant from the double-resistant mutant AAr-9 provides a new advantageous method for the production of L-citrulline. The increase in arginine and citrulline production is discussed.

Arginine↗