Riedijk Maaike A, Stoll Barbara, Chacko Shaji, Schierbeek Henk, Sunehag Agneta L, van Goudoever Johannes B, Burrin Douglas G
Department of Pediatrics, Division of Neonatology, Erasmus Medical Center-Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands.
Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3408-13. doi: 10.1073/pnas.0607965104. Epub 2007 Feb 21.
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-(13)C]methionine and [(2)H(3)]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 approximately 27% and approximately 23% of whole-body fluxes, respectively. The methionine used by the GIT was metabolized into homocysteine (31%), CO(2) (40%), or tissue protein (29%). Cystathionine beta-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.
蛋氨酸是一种必需的含硫氨基酸，是合成同型半胱氨酸和半胱氨酸的关键前体。对成年人类的研究表明，内脏组织分别通过转甲基作用和转硫作用将膳食蛋氨酸转化为同型半胱氨酸和半胱氨酸。对仔猪的研究表明，膳食必需氨基酸在胃肠道组织（GIT）中发生显著代谢，但蛋氨酸在GIT中的代谢命运尚不清楚。我们在此表明，在植入门静脉和动脉导管并喂食奶粉的仔猪中，20%的膳食蛋氨酸摄入量由GIT代谢。基于对十二指肠内和静脉输注[1-(13)C]蛋氨酸和[(2)H(3)]蛋氨酸的分析，我们发现十二指肠输注示踪剂期间全身蛋氨酸的转甲基作用和再甲基化率显著高于静脉输注。首过内脏代谢分别占全身转甲基作用和再甲基化作用的18%和43%。在GIT中证实了显著的转甲基作用和转硫作用，分别约占全身通量的27%和约23%。GIT使用的蛋氨酸代谢为同型半胱氨酸（31%）、CO(2)（40%）或组织蛋白（29%）。胱硫醚β-合酶mRNA和活性存在于包括肠上皮细胞在内的多个GIT中，但显著低于肝脏。我们得出结论，GIT消耗20%的膳食蛋氨酸，是同型半胱氨酸净产生的重要部位。此外，GIT是全身转甲基作用和转硫作用的重要部位，这两条途径占GIT使用的蛋氨酸的大部分。
