Glutamine: precursor or nitrogen donor for citrulline synthesis?
Although glutamine is considered the main precursor for citrulline synthesis, the current literature does not differentiate between the contribution of glutamine carbon skeleton vs. nonspecific nitrogen (i.e., ammonia) and carbon derived from glutamine oxidation. To elucidate the role of glutamine and nonspecific nitrogen in the synthesis of citrulline, l-[2-(15)N]- and l-[5-(15)N]glutamine and (15)N-ammonium acetate were infused intragastrically in mice. The amino group of glutamine labeled the three nitrogen groups of citrulline almost equally. The amido group and ammonium acetate labeled the ureido and amino groups of citrulline, but not the delta-nitrogen. D(5)-glutamine also infused in this arm of the study, which traces the carbon skeleton of glutamine, was utilized poorly, accounting for only 0.2-0.4% of the circulating citrulline. Dietary glutamine nitrogen (both N groups) incorporation was 25-fold higher than the incorporation of its carbon skeleton into citrulline. To investigate the relative contributions of the carbon skeleton and nonspecific carbon of glutamine, arginine, and proline to citrulline synthesis, U-(13)C(n) tracers of these amino acids were infused intragastrically. Dietary arginine was the main precursor for citrulline synthesis, accounting for approximately 40% of the circulating citrulline. Proline contribution was minor (3.4%), and glutamine was negligible (0.4%). However, the glutamine tracer resulted in a higher enrichment in the ureido group, indicating incorporation of nonspecific carbon from glutamine oxidation into carbamylphosphate used for citrulline synthesis. In conclusion, dietary glutamine is a poor carbon skeleton precursor for the synthesis of citrulline, although it contributes both nonspecific nitrogen and carbon to citrulline synthesis.
Marini
Juan C
JC
Children's Nutrition Research Center, Department of Pediatrics, United States Department of Agriculture/Agricultural Research Service, 1100 Bates Street, Houston, TX 77030, USA. marini@bcm.edu
Didelija
Inka Cajo
IC
Castillo
Leticia
L
Lee
Brendan
B
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000097:blood / Q000378:metabolism*; D002247:Carbon Isotopes / Q000097:blood / Q000494:pharmacology; D002956:Citrulline / Q000096:biosynthesis* / Q000097:blood; D041981:Gastrointestinal Tract / Q000378:metabolism*; D005973:Glutamine / Q000097:blood / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008813:Mice, Inbred ICR; D009584:Nitrogen / Q000378:metabolism; D009587:Nitrogen Isotopes / Q000097:blood / Q000494:pharmacology; D011392:Proline / Q000097:blood / Q000378:metabolism*; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms
D002247:Carbon Isotopes; D009587:Nitrogen Isotopes; D005973:Glutamine; D002956:Citrulline; D000641:Ammonia; D001120:Arginine; D011392:Proline; D009584:Nitrogen
Nat Genet. 1995 Oct;11(2):185-90
7550347
Biochem J. 1979 Mar 15;178(3):589-96
454367
Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1764-71
17925451
Am J Clin Nutr. 2007 Jan;85(1):167-72
17209193
Am J Clin Nutr. 2008 May;87(5):1282-9
18469251
Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E683-90
16684848
Biochem J. 1985 Dec 1;232(2):329-34
2868709
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8612-6
2236071
J Nutr. 2006 Jan;136(1):202-6
16365083
Pediatr Res. 1998 Apr;43(4 Pt 1):442-51
9544996
Arch Biochem Biophys. 1991 Nov 15;291(1):1-8
1929423
J Inherit Metab Dis. 1994;17(6):691-703
7707692
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13681-6
16157883
JPEN J Parenter Enteral Nutr. 1997 Nov-Dec;21(6):316-23
9406127
Biochim Biophys Acta. 1994 May 25;1200(1):73-8
8186236
Am J Physiol. 1997 Jun;272(6 Pt 1):G1382-90
9227473
J Biol Chem. 1989 Mar 5;264(7):4038-44
2917987
J Biol Chem. 1989 Jun 15;264(17):10205-9
2722865
J Nutr. 1996 Apr;126(4):878-86
8613891
Annu Rev Nutr. 1995;15:133-59
8527215
Biochim Biophys Acta. 1991 May 17;1092(3):304-10
2049401
Am J Physiol. 1996 Nov;271(5 Pt 2):R1149-55
8945947
Biochem J. 1994 Apr 1;299 ( Pt 1):115-21
8166628
J Biol Chem. 1974 Aug 25;249(16):5070-9
4605420
Physiol Rev. 1990 Jul;70(3):701-48
2194222
Lab Anim. 2006 Jul;40(3):275-81
16803644
JPEN J Parenter Enteral Nutr. 2007 Sep-Oct;31(5):343-48; discussion 349-50
17712141
Am J Clin Nutr. 2006 Jan;83(1):115-23
16400059
Am J Physiol Endocrinol Metab. 2007 Sep;293(3):E811-8
17595215
J Biol Chem. 2005 Oct 28;280(43):36409-16
16096275
Biochim Biophys Acta. 1976 May 28;428(3):600-10
1276171
Int J Colorectal Dis. 1999 Apr;14(2):86-94
10367253
JPEN J Parenter Enteral Nutr. 1994 Sep-Oct;18(5):422-6
7815673
Aliment Pharmacol Ther. 2008 Jun;27(12):1300-10
18331613
Pediatrics. 1984 Jun;73(6):879
6728593
Am J Physiol Endocrinol Metab. 2006 Sep;291(3):E582-6
16608884
JPEN J Parenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):137S-146S
2119459
Biochem J. 1967 Aug;104(2):557-63
6048797
Pediatr Res. 1990 Sep;28(3):261-5
2235124
Am J Physiol. 1981 Dec;241(6):E473-80
7325229
Med Hypotheses. 2010 Jun;74(6):1055-8
20089363
Am J Physiol Gastrointest Liver Physiol. 2005 Oct;289(4):G679-85
15933220
Curr Opin Clin Nutr Metab Care. 2009 Jul;12(4):398-403
19474715
Am J Physiol. 1993 Oct;265(4 Pt 1):E532-9
8238326
J Biochem. 1994 Oct;116(4):721-7
7883744
Life Sci. 2007 Apr 24;80(20):1846-50
17363008
Am J Physiol Endocrinol Metab. 2004 Sep;287(3):E454-62
15149954
Biochem J. 1989 Apr 1;259(1):131-8
2497728
Clin Nutr. 2008 Jun;27(3):321-7
18501998
Crit Care Med. 2007 Sep;35(9 Suppl):S568-76
17713411
Biochem J. 1977 Jan 15;162(1):147-56
849273
Arch Biochem Biophys. 1976 Aug;175(2):670-6
958325
Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1061-7
17901164
Am J Hypertens. 2010 Jan;23(1):12-6
19851298
Proc Natl Acad Sci U S A. 1980 Sep;77(9):5221-5
6933554
Am J Physiol Endocrinol Metab. 2003 May;284(5):E915-22
12527558