title: Evidence for a metabolic shift of arginine metabolism in sickle cell disease.
abstract: Over the last few years, a pivotal role has been ascribed to reduced nitric oxide (NO) availability as a contributing factor to the vaso-occlusive process of sickle cell disease. We investigated whether arginine metabolism in sickle cell patients is different from healthy controls. Blood samples were drawn by venipuncture in the fasting state from 8 clinically asymptomatic HbSS patients and 14 race-matched HbAA controls. HbSS patients had decreased plasma arginine (p=0.001) and increased proline (p=0.015) levels as compared to controls. Ratios of arginine to ornithine (p<0.001), proline (p<0.001), glutamate (p=0.003), and citrulline (p=0.026) were lower in HbSS patients. There were significant correlations of ornithine (r(s)=-0.71, p=0.047), citrulline (r(s)=-0.79, p=0.021), arginine/ornithine (r(s)=0.93, p=0.001), and arginine/citrulline (r(s)=0.81, p=0.015) to hemoglobin and of arginine/proline (r(s)=-0.76, p=0.028) and citrulline (r(s)=0.71, p=0.048) to leukocyte counts. These data indicate that in clinically asymptomatic sickle cell patients increased arginine metabolism is shifted to the arginase pathway and that this seems to be more profound in patients with higher hemolytic rates and leukocyte counts.
authors.affiliation: Department of Internal Medicine (9B), Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. jschnog@wanadoo.nl
authors.forename: John-John B
authors.initials: JJ
authors.lastname: Schnog
authors.forename: Esther H
authors.initials: EH
authors.lastname: Jager
authors.forename: Fey P L
authors.initials: FP
authors.lastname: van der Dijs
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Duits
authors.forename: Han
authors.initials: H
authors.lastname: Moshage
authors.forename: Fred D
authors.initials: FD
authors.lastname: Muskiet
authors.forename: Frits A J
authors.initials: FA
authors.lastname: Muskiet
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D000755:Anemia, Sickle Cell / Q000097:blood*; D001119:Arginase / Q000097:blood; D001120:Arginine / Q000097:blood*; D016022:Case-Control Studies; D006441:Hemoglobin A / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006454:Hemoglobins; D006801:Humans; D008875:Middle Aged; D013223:Statistics as Topic
chemical_list: D000596:Amino Acids; D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D006441:Hemoglobin A; D001120:Arginine; D001119:Arginase