Threonine metabolism in the intestine of mice: loss of mucin 2 induces the threonine catabolic pathway.
OBJECTIVE
Previous studies have shown that the intestine uses a major part of the dietary threonine intake for the synthesis of the structural component of the protective intestinal mucus layer, the secretory mucin Muc2. In this context, the high intestinal demand for dietary threonine probably results from its incorporation into secretory mucins rich in threonine residues. Therefore, we compared threonine utilization in the colon of Muc2 knockout (Muc2-/-) and wild-type (Muc2+/+) mice to investigate the intestinal dietary threonine metabolism in the absence of Muc2, which results in inflammation of the colon.


METHODS
Concentrations and isotopic enrichment of threonine were measured by gas chromatography-isotope ratio mass spectrometry in the serum, colon, and colonic content of mice given a bolus [U-(13)C]threonine enterally.


RESULTS
We retrieved 37.8% and 40.9% of dietary threonine in Muc2 +/+ and Muc2 -/- mice, respectively, either as free or incorporated threonine. There were no major differences in the availability and concentration of free or incorporated threonine recovered in both serum and colon in both types of mice. However, the Muc2 -/- mice did show overall significantly higher threonine oxidation rates compared with Muc2 +/+ mice.


CONCLUSIONS
In the absence of Muc2, dietary threonine is mainly used for constitutive protein synthesis or becomes a substrate for metabolic oxidation. This indicates that inflammation also requires high threonine amounts.
van der Sluis
Maria
M
Department of Pediatrics, Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Schaart
Maaike W
MW
de Koning
Barbara A E
BA
Schierbeek
Henk
H
Velcich
Anna
A
Renes
Ingrid B
IB
van Goudoever
Johannes B
JB
D000818:Animals; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007420:Intestine, Large / Q000378:metabolism*; D007554:Isotopes; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000235:genetics / Q000378:metabolism*
D007554:Isotopes; C524626:Muc2 protein, mouse; D055262:Mucin-2; D013912:Threonine