Background Arginine plays an important role in several metabolic pathways as well as being a substrate for pro-tein synthesis. Arginine metabolism involves multi-com-partment processes that vary according to cell type/body organ. Enterocytes are a major site for arginine synthesis. The key amino acid (AA) metabolites of arginine synthesis pathways in the enterocytes of very preterm infants (VPIs) include glutamine, glutamate and proline with interme-diates ornithine and citrulline. The key arginine degrada-tion AA metabolite in the liver is ornithine. In contrast to these metabolically active AAs, histidine is presumed to be a metabolically inert AA and hence probably a useful indicator of non-metabolic factors (e.g. renal elimination). Newborn infants are dependent on enteral milk proteins for the AAs required for enterocyte arginine synthesis. However VPIs are dependent on parenteral nutrition (PN) and therefore parenteral AA for the first 2 weeks of life un-til milk feeds are established.
Methods Secondary analysis was performed on the plasma AA data collected during a previously published randomised controlled trial.1 Plasma AA were collected in the second week of life in infants randomised to receive either 3.2 g/kg/d (standard) or 4.3 g/kg/d (high dose) par-enteral AA.2 A Spearman’s correlation analysis was run on the plasma data for the AA subgroups involved in argi-nine metabolic pathways to assess their relationship with arginine in the VPI population. The data also underwent multivariate regression analysis (combining both groups) to test if any of these AA significantly predicted plasma arginine levels.
Results Plasma AA levels were performed on median (IQR) day 9 (8-10) in both groups. Mean (95% confidence intervals) plasma arginine levels were 41 (25-57) and 35 (22-46) micromol/litre in the high and standard AA dose groups respectively (p=0.21) well below the reference range minimum (57µmol/L). Data analysis showed that arginine had the strongest positive correlation with or-nithine, r=0.602, n=107, p<0.001, followed by gluta-mine, r=0.564, n=107, p<0.001. A significant regression model was found [F(3,103)=24.318, p<0.001] with an R2=0.415
Conclusion Plasma ornithine, glutamate and histidine are significant predictors of plasma arginine in PN depen-dent VPIs. This indicates that there are both metabolic and non-metabolic factors that play a role in determination of plasma arginine levels.
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