ARS | Publication request: Glutamine: precursor or nitrogen donor for citrulline synthesis?

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: April 19, 2010
Publication Date: April 20, 2010
Citation: Marini, J.C., Didelija, I.C., Castillo, L., Lee, B. 2010. Glutamine: precursor or nitrogen donor for citrulline synthesis? [abstract]. Journal of Federation of American Societies for Experimental Biology. 24:740.14.

Technical Abstract: Glutamine (Gln) is considered the main precursor for citrulline (Cit) synthesis, but no attempts have been made to differentiate the contribution of Gln carbon (Gln-C) skeleton vs. the nonspecific contribution through NH3 and CO2. To study the contribution of dietary Gln-N to the synthesis of Cit, the incorporation of 2-15N and 5-15N Gln, and 15N ammonium into the 3 N groups of Cit was determined in conscious mice. D5 and U-13C5 Gln were used to determine the incorporation of Gln-C. The contribution of dietary arginine (Arg) and proline (Pro) were also determined by the infusion of U-13Cn tracers. The 2-15N Gln tracer labeled to a similar extent the 3 N positions of Cit, while 5-15N Gln and 15N ammonium tracers mainly labeled the ureido group. The total incorporation of 2-15N and 5-15N exceeded 25-fold the incorporation of the D5 tracer. Dietary Arg was the main precursor for Cit synthesis (40% of RaCit), followed by Pro and Gln (3.4 and 0.4% of RaCit, respectively). The incorporation of a single 13C into Cit from Gln and Pro, but not from Arg, was detected. This represents the oxidation of Gln and Pro in enterocytes, with the subsequent utilization of 13CO2 for the synthesis of carbamylphosphate. In conclusion, Gln is not a carbon skeleton precursor for Cit synthesis, but donates nonspecific N and C for its synthesis. Dietary Arg is the main carbon skeleton precursor for Cit synthesis.