Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract

doi:10.1073/pnas.0607965104

Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract

*Department of Pediatrics, Division of Neonatology, Erasmus Medical Center–Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands; and
^†U.S. Department of Agriculture–Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates Street, Houston, TX 77030

Edited by David H. Baker, University of Illinois at Urbana–Champaign, Urbana, IL, and approved December 27, 2006 (received for review September 12, 2006)

Abstract

Methionine is an indispensable sulfur amino acid that functions as a key precursor for the synthesis of homocysteine and cysteine. Studies in adult humans suggest that splanchnic tissues convert dietary methionine to homocysteine and cysteine by means of transmethylation and transsulfuration, respectively. Studies in piglets show that significant metabolism of dietary indispensable amino acids occurs in the gastrointestinal tissues (GIT), yet the metabolic fate of methionine in GIT is unknown. We show here that 20% of the dietary methionine intake is metabolized by the GIT in piglets implanted with portal and arterial catheters and fed milk formula. Based on analyses from intraduodenal and intravenous infusions of [1-¹³C]methionine and [²H₃]methionine, we found that the whole-body methionine transmethylation and remethylation rates were significantly higher during duodenal than intravenous tracer infusion. First-pass splanchnic metabolism accounted for 18% and 43% of the whole-body transmethylation and remethylation, respectively. Significant transmethylation and transsulfuration was demonstrated in the GIT, representing ≈27% and ≈23% of whole-body fluxes, respectively. The methionine used by the GIT was metabolized into homocysteine (31%), CO₂ (40%), or tissue protein (29%). Cystathionine β-synthase mRNA and activity was present in multiple GITs, including intestinal epithelial cells, but was significantly lower than liver. We conclude that the GIT consumes 20% of the dietary methionine and is a significant site of net homocysteine production. Moreover, the GITs represent a significant site of whole-body transmethylation and transsulfuration, and these two pathways account for a majority of methionine used by the GITs.

Footnotes

^‡To whom correspondence should be addressed. E-mail: dburrin{at}bcm.tmc.edu
Author contributions: J.B.v.G. and D.G.B. designed research; M.A.R., B.S., and D.G.B. performed research; M.A.R., B.S., S.C., and H.S. contributed new reagents/analytic tools; M.A.R., H.S., A.L.S., and D.G.B. analyzed data; and M.A.R., J.B.v.G., and D.G.B. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0607965104/DC1.
Abbreviations:

GIT,

gastrointestinal tissues;

ID,

intraduodenal;

IV,

intravenous;

MPE,

mole percent excess;

CBS,

cystathionine β-synthase;

SAM,

S-adenosylmethionine.