Increased serum levels of L-arginine in ulcerative colitis and correlation with disease severity.

Hong SK, Maltz BE, Coburn LA, Slaughter JC, Chaturvedi R, Schwartz DA, Wilson KT
Inflamm Bowel Dis. 2010 16 (1): 105-11

PMID: 19637336 · PMCID: PMC2795785 · DOI:10.1002/ibd.21035

BACKGROUND - L-arginine (L-Arg) is a semi-essential amino acid that is the substrate for both nitric oxide and polyamine synthesis. Cellular uptake of L-Arg is an active transport process that is subject to competitive inhibition by L-ornithine (L-Orn) and L-lysine (L-Lys). We investigated L-Arg utilization in patients with ulcerative colitis (UC).

METHODS - Serum was collected from 14 normal controls and 22 UC patients with pancolitis of moderate or severe activity by histopathology score. The Mayo Disease Activity Index (DAI) and endoscopy subscore were assessed. Serum amino acid levels were measured by high-performance liquid chromatography. Arginine availability index (AAI) was defined as [L-Arg]/([L-Orn] + [L-Lys]).

RESULTS - Serum L-Arg levels were significantly associated with histopathologic grade (P = 0.001). L-Arg levels were increased in subjects with severe colitis when compared to those with moderate colitis or normal mucosa. L-Orn + L-Lys levels were also increased in severe colitis, so that AAI was not significantly increased. L-Arg levels were also strongly associated with the endoscopy subscore (P < 0.001). There was a strong correlation between DAI and L-Arg levels (r = 0.656, P < 0.001).

CONCLUSIONS - Serum L-Arg levels correlate with UC disease severity but availability is not increased due to competitive inhibition by L-Orn and L-Lys. Our findings suggest that L-Arg uptake by cells in the inflamed colon is defective, which may contribute to the pathogenesis of UC. Studies delineating the mechanism of uptake inhibition could enhance our understanding of UC or lead to novel treatment options.

MeSH Terms (15)

Adolescent Adult Aged Arginine Biomarkers Case-Control Studies Chromatography, High Pressure Liquid Colitis, Ulcerative Colon Female Humans Male Middle Aged Prospective Studies Young Adult

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