Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet.

BACKGROUND & AIMS: It is not known whether arginine homeostasis is negatively affected by a "long term" dietary restriction of arginine and its major precursors in healthy adults. To assess the effects of a 4-week arginine- and precursor-free dietary intake on the regulatory mechanisms of arginine homeostasis in healthy subjects. METHODS: Ten healthy adults received a complete amino acid diet for 1 week (control diet) and following a break period, six subjects received a 4-week arginine, proline, glutamate and aspartate-free diet (APF diet). The other four subjects continued for 4 weeks with the complete diet. On days 4 and 7 of the first week and days 25 and 28 of the 4-week period, the subjects received 24-h infusions of arginine, citrulline, leucine and urea tracers. RESULTS: During the 4-week APF, plasma arginine fluxes for the fed state, were significantly reduced. There were no significant differences for citrulline, leucine or urea fluxes. Arginine de novo synthesis was not affected by the APF intake. However, arginine oxidation was significantly decreased. CONCLUSIONS: In healthy adults, homeostasis of arginine under a long term arginine- and precursor-free intake is achieved by decreasing catabolic rates, while de novo arginine synthesis is maintained.

Arginine and nitric oxide metabolism in critically ill septic pediatric patients.

OBJECTIVE: To investigate whole body, arginine metabolism and nitric oxide synthesis rates in septic, critically ill pediatric patients. DESIGN: Prospective study. SETTING: Pediatric intensive care unit at a general hospital. PATIENTS: Ten consecutive septic patients age 6-16 yrs. INTERVENTIONS: Septic patients received an 8-hr primed, constant intravenous tracer infusion of L-[guanidino-15N2]arginine, L-[1-13C]leucine, and [13C]urea. A 24-hr urine collection was obtained for determination of [15N]nitrate enrichment (15NO3(-)) and urinary nitrogen. The next day they received an infusion of L-[5-13C]arginine and L-[5-13C-ureido, 5,5, 2H2]citrulline. Blood samples were obtained for determination of plasma isotopic enrichment of the tracers given and of derived [15N]citrulline (nitric oxide synthesis), L-[13C-guanidino 5,5, 2H2]arginine (M+3 arg) (arginine synthesis), and [15N]urea (urea formation). Data are compared with historic controls from studies in healthy young adults. MEASUREMENTS AND MAIN RESULTS: Plasma arginine fluxes were 67 +/- 21 and 72 +/- 17 micromol x kg(-1) x hr(-1), respectively, for the [15N2 guanidino] and the [13C] arginine labels, which were not different from reported adult values. The rates of arginine oxidation were 22.9 +/- 10.8 micromol x kg(-1) x hr(-1) and were higher than arginine synthesis rates of 9.6 +/- 4.2 micromol x kg(-1) x hr(-1) (p <.01); therefore, these patients were in a negative arginine balance. The rates of nitric oxide synthesis as estimated by the [15N]citrulline method were 1.58 +/- 0.69 micromol x kg(-1) x hr(-1) for septic patients and higher (p <.05) than values of 0.96 +/- 0.1 micromol x kg(-1) x hr(-1) in healthy adults. Septic patients were in a negative protein (leucine) balance of about -1.00 +/- 0.40 g x kg(-1) x day(-1). CONCLUSIONS: Homeostasis of plasma arginine in septic patients was impaired compared with reported adult values. The rates of arginine oxidation were increased whereas net arginine synthesis was unchanged, leading to a negative arginine balance. The rates of nitric oxide synthesis and the fraction of plasma arginine used for nitric oxide and urea formation were increased. These findings suggest that under condition of sepsis, arginine becomes essential in critically ill children.