Asymmetric dimethylation and citrullination of proteinic arginine and homoarginine synthesis in human Helicobacter pylori infection

• Published in: Amino acids Vol. 51; no. 6; pp. 961 - 971
• Main Authors: Bollenbach, Alexander, Hanff, Erik, Brunner, Gorig, Tsikas, Dimitrios
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.06.2019; Springer Nature B.V
• Subjects: Adults; Age; Analytical Chemistry; Arginine; Asymmetry; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; blood proteins; blood serum; Citrulline; Dilution; elderly; Females; Gas chromatography; gas chromatography-mass spectrometry; Geriatrics; Guanidine; guanidines; Helicobacter pylori; humans; hydrochloric acid; Infections; isotope dilution technique; Life Sciences; Lysine; Males; Mass spectrometry; Mass spectroscopy; Methylation; Morbidity; mortality; Neurobiology; Nitric oxide; Older people; Original Article; Ornithine; Platelet aggregation; Proteins; Proteolysis; Proteomics; Quantitation; Risk analysis; Risk factors; seroprevalence; Serum proteins; stable isotopes; Statistical methods; Synthesis; Citrullination; ADMA; Serum; Homoarginine; Protein; Arg; Helicobacter pylori
• ISSN: 0939-4451; 1438-2199; 1438-2199
• DOI: 10.1007/s00726-019-02737-y

The importance of l -arginine (Arg) and relatives, including l -homoarginine (hArg) and asymmetric dimethylarginine (ADMA), in humans infected with Helicobacter pylori ( Hp ) is little understood. ADMA is produced by asymmetric dimethylation of the guanidine group of Arg residues in certain proteins and is released by proteolysis. High concentrations of circulating free ADMA are considered a risk factor for morbidity and mortality in adults. This risk is considered to arise from the inhibition of the synthesis of nitric oxide (NO), which is a potent vasodilator and inhibitor of platelet aggregation. In the present study, we quantified by stable isotope dilution gas chromatography–mass spectrometry (GC–MS) the concentration of free (f) and total (t) ADMA, Arg, hArg, lysine (Lys) and the sum of citrulline (Cit) and ornithine (Orn) (6 M HCl, 20 h, 110 °C) in serum samples of apparently healthy elderly subjects ( n  = 27; age, 31–105 years) who were tested for Hp infection. Nine subjects (5 males, 4 females) were found to be Hp seropositive ( Hp+ ) and 18 subjects (8 males, 9 females) were found to be Hp seronegative ( Hp ‒). Proteinic (p) concentrations were determined by difference. fADMA (0.493 ± 0.068 vs 0.466 ± 0.081 µM, P  = 0.382), pADMA (113 ± 73 vs 76 ± 59 nM, P  = 0.169) and tADMA (0.606 ± 0.126 vs 0.543 ± 0.121 µM, P  = 0.280) serum concentrations were found not to differ between the Hp + and Hp − subjects. Serum concentrations of fArg (162 ± 30 vs 177 ± 36 µM, P  = 0.471), fhArg (1.600 ± 0.638 vs 1.831 ± 0.742 µM, P  = 0.554), and fLys (388 ± 170 vs 395 ± 149 µM, P  = 0.700) also did not differ statistically between Hp+ and Hp − subjects. tArg (12.4 ± 1.49 vs 13.0 ± 1.33 mM, P  = 0.190), tLys (23.0 ± 2.65 vs. 23.9 ± 2.66 mM, P  = 0.456) and tCit + Orn (2.53 ± 0.76 vs 2.63 ± 0.85 mM, P  = 0.817) did not differ between Hp+ and Hp ‒ subjects as well. phArg concentration was close to the limit of quantitation of the method ( Hp+ : 30 ± 210 nM; Hp −: 42 ± 205 nM), suggesting that hArg is virtually absent in serum proteins of the investigated subjects. pCit + Orn did not differ between infected and non-infected subjects. Our study suggests that Hp infection is not associated with elevated asymmetric dimethylation and citrullination of Arg proteins present in the serum or with the hArg synthesis from free Arg in elderly subjects. However, asymmetric Arg dimethylation was found to correlate inversely with Arg citrullination in Hp − ( r 2  = 0.408, P  = 0.004) but not in Hp+ ( r 2  = 0.065, P  = 0.506), with Arg citrullination decreasing and Arg asymmetric dimethylation increasing with subjects’ age.