Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs

Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1239-50. doi: 10.1152/ajpendo.91021.2008. Epub 2009 Mar 17.


We recently showed that the developing gut is a significant site of methionine transmethylation to homocysteine and transsulfuration to cysteine. We hypothesized that sulfur amino acid (SAA) deficiency would preferentially reduce mucosal growth and antioxidant function in neonatal pigs. Neonatal pigs were enterally fed a control or an SAA-free diet for 7 days, and then whole body methionine and cysteine kinetics were measured using an intravenous infusion of [1-(13)C;methyl-(2)H(3)]methionine and [(15)N]cysteine. Body weight gain and plasma methionine, cysteine, homocysteine, and taurine and total erythrocyte glutathione concentrations were markedly decreased (-46% to -85%) in SAA-free compared with control pigs. Whole body methionine and cysteine fluxes were reduced, yet methionine utilization for protein synthesis and methionine remethylation were relatively preserved at the expense of methionine transsulfuration, in response to SAA deficiency. Intestinal tissue concentrations of methionine and cysteine were markedly reduced and hepatic levels were maintained in SAA-free compared with control pigs. SAA deficiency increased the activity of methionine metabolic enzymes, i.e., methionine adenosyltransferase, methionine synthase, and cystathionine beta-synthase, and S-adenosylmethionine concentration in the jejunum, whereas methionine synthase activity increased and S-adenosylmethionine level decreased in the liver. Small intestine weight and protein and DNA mass were lower, whereas liver weight and DNA mass were unchanged, in SAA-free compared with control pigs. Dietary SAA deficiency induced small intestinal villus atrophy, lower goblet cell numbers, and Ki-67-positive proliferative crypt cells in association with lower tissue glutathione, especially in the jejunum. We conclude that SAA deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids, Sulfur / blood*
  • Amino Acids, Sulfur / deficiency*
  • Animals
  • Animals, Newborn
  • Cell Division / physiology
  • Cysteine / metabolism
  • Cysteine / pharmacokinetics
  • Enteral Nutrition
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Female
  • Glutathione / metabolism
  • Goblet Cells / cytology
  • Goblet Cells / metabolism
  • Homocysteine / metabolism
  • Homocysteine / pharmacokinetics
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / growth & development*
  • Intestinal Mucosa / metabolism*
  • Iodine Radioisotopes
  • Methionine / metabolism*
  • Methionine / pharmacokinetics
  • Methionine Adenosyltransferase / metabolism
  • Methylation
  • Models, Biological
  • Nitrogen Isotopes
  • Organ Size
  • Oxidation-Reduction
  • Sus scrofa
  • Tritium
  • Up-Regulation / physiology


  • Amino Acids, Sulfur
  • Iodine Radioisotopes
  • Nitrogen Isotopes
  • Homocysteine
  • Tritium
  • Methionine
  • Methionine Adenosyltransferase
  • Glutathione
  • Cysteine