Human splanchnic amino-acid metabolism

Abstract

Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery. The difference between arterial and venous concentrations of 21 amino acids was determined using liquid chromatography as a measure of amino-acid metabolism across a given organ. Whereas glutamine was significantly taken up by the small intestine (121.0 ± 23.8 µmol/L; P < 0.0001), citrulline was released (−36.1 ± 4.6 µmol/L; P < 0.0001). This, however, was not seen for the colon. Interestingly, the liver showed a small, but a significant uptake of citrulline from the circulation (4.8 ± 1.6 µmol/L; P = 0.0138) next to many other amino acids. The kidneys showed a marked release of serine and alanine into the circulation (−58.0 ± 4.4 µmol/L and −61.8 ± 5.2 µmol/L, P < 0.0001), and a smaller, but statistically significant release of tyrosine (−12.0 ± 1.3 µmol/L, P < 0.0001). The spleen only released taurine (−9.6 ± 3.3 µmol/L; P = 0.0078). Simultaneous blood sampling in different veins provides unique qualitative and quantitative information on integrative amino-acid physiology, and reveals that the well-known intestinal glutamine–citrulline pathway appears to be functional in the small intestine but not in the colon.

Plasma biomarkers of small intestine adaptations in obesity-related metabolic alterations

“…Citrulline is a key intermediate in the urea cycle but liver remains a negligible contributor to its circulating levels. Enterocytes are the main site of citrulline biosynthesis from dietary and plasma amino acid precursors (i.e., arginine, ornithine, glutamine, glutamate or proline) [9][10][11][12][13]. Citrulline catabolism remains stable in absence of kidney disease and the small intestine therefore appears as the most important determinant of plasma citrulline levels.…”

Absorptive transport of amino acids by the rat colon

“…We conclude that a significant component of serosal AA accumulation represents release from a relatively stable pool of AAs within the epithelial cell component of the mucosa, possibly derived from ongoing synthesis/transformation of intracellular AAs or catabolism of cytosolic protein stores. The preferential release of Ala from colonic epithelial cells may account for the observed enrichment of Ala in the inferior mesenteric venous plasma exiting the human colon (35), supporting the hypothesis that the colon, like the liver and skeletal muscle, adds appreciable quantities of Ala to the systemic circulation. These measurements of arteriovenous differences also suggested smaller net releases of Gly, Lys, and taurine by the human colon, although these differences did not reach statistical significance, perhaps related to a small data set (35).…”

“…The preferential release of Ala from colonic epithelial cells may account for the observed enrichment of Ala in the inferior mesenteric venous plasma exiting the human colon (35), supporting the hypothesis that the colon, like the liver and skeletal muscle, adds appreciable quantities of Ala to the systemic circulation. These measurements of arteriovenous differences also suggested smaller net releases of Gly, Lys, and taurine by the human colon, although these differences did not reach statistical significance, perhaps related to a small data set (35). Our result suggest that colonic epithelial cells also add AAs, especially Ala, to the fecal fluid.…”

Gas chromatography‑time of flight/mass spectrometry‑based metabonomics of changes in the urinary metabolic profile in osteoarthritic rats

“…In the present study, GC-TOF/MS was used from the perspective of metabonomics to explore the pathogenesis of OA. A total of 23 potential biomarkers were identified, including alanine, α-ketoglutarate, asparagine, maltose and glutamine, all of which may be correlated to amino acid metabolism, energy metabolism, fatty acid metabolism, vitamin B 6 metabolism or nucleic acid metabolism ( 27 – 29 ).…”