Increased serum levels of L-arginine in ulcerative colitis and correlation with disease severity.
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.
Hong
Shih-Kuang S
SK
Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee 37232-0252, USA.
Maltz
Brad E
BE
Coburn
Lori A
LA
Slaughter
James C
JC
Chaturvedi
Rupesh
R
Schwartz
David A
DA
Wilson
Keith T
KT
D000293:Adolescent; D000328:Adult; D000368:Aged; D001120:Arginine / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000097:blood* / Q000175:diagnosis*; D003106:Colon / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
D015415:Biomarkers; D001120:Arginine