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L-Arginine Availability and Metabolism Is Altered in Ulcerative Colitis.
Lori A Coburn1, Sara N Horst, Margaret M Allaman
1*Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee;†Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;‡Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee;§University of Central Florida, College of Medicine, Orlando, Florida;‖Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; and¶Vanderbilt Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee.
Ulcerative colitis (UC) patients show decreased tissue L-arginine (L-Arg) due to impaired cell uptake and increased NOS2 consumption. This, along with reduced arginase 1 (ARG1) expression, points to dysregulated L-Arg metabolism in UC.
Area of Science:
- Gastroenterology
- Molecular Biology
- Biochemistry
Background:
- L-arginine (L-Arg) is crucial for nitric oxide (NO) and arginase (ARG) pathways.
- Cellular uptake of L-Arg occurs via cationic amino acid transporters (SLC7).
- L-Arg and arginase 1 activity are linked to epithelial restitution.
Purpose of the Study:
- To investigate alterations in L-Arg, related amino acids, and metabolic enzymes in ulcerative colitis (UC).
Main Methods:
- Serum and colonic tissues from 137 UC patients and 38 controls were analyzed.
- Amino acid levels were quantified using high-performance liquid chromatography.
- Messenger RNA (mRNA) levels of relevant enzymes and transporters were measured via real-time PCR.
Main Results:
- UC patients had decreased tissue L-Arg, increased L-citrulline (L-Cit), and a higher L-Cit/L-Arg ratio in active disease.
- mRNA levels of SLC7A2 and ARG1 were decreased, while ARG2 and NOS2 were increased in active UC colonic tissue.
- Similar mRNA expression changes were observed in Crohn's disease tissues.
Conclusions:
- Ulcerative colitis is characterized by diminished tissue L-Arg, linked to reduced cellular uptake and elevated NOS2 activity.
- Decreased ARG1 expression further contributes to dysregulated L-Arg availability and metabolism in UC.
- These metabolic shifts in L-Arg pathways may play a significant role in UC pathogenesis.
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