title: Sulfur amino acid metabolism limits the growth of children living in environments of poor sanitation.
abstract: Environmental enteropathy has been identified as a cause of poor growth in children living in low-income countries, but a mechanism has not been well defined. We suggest changes in sulfur amino acid metabolism can in part explain the poor growth and possibly the histological changes in the small bowel, which is the hallmark of environmental enteropathy. In environments of poor sanitation, where infection is common, we propose increased oxidative stress drives methionine metabolism toward cystathionine synthesis. This "cystathionine siphon" limits sulfur amino acids from participating in critical protein synthesis pathways. Increased expression of cystathionine β-synthase (CBS) could be one mechanism, as lipopolysaccharide and TNFα increase activity of this enzyme in vivo. CBS catalyzes the first of two steps in the transsulfuration pathway that converts homocysteine to cysteine. As enterocytes are one of the most rapidly proliferating cells in the body, we suggest diminished translation might also be important in the barrier failure observed in environmental enteropathy. Identifying sulfur amino acid metabolism as a mechanism leading to poor growth provides a new testable hypothesis for the undernutrition observed in children living in settings of poor sanitation.
authors.affiliation: Division of Pediatric Surgery, Rady Children's Hospital, School of Medicine, Department of Surgery, University of California, San Diego, La Jolla, CA 92093-0739, USA. Sbickler@ucsd.edu
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Bickler
authors.forename: Jason
authors.initials: J
authors.lastname: Ring
authors.forename: Antonio
authors.initials: A
authors.lastname: De Maio
mesh_terms: D000603:Amino Acids, Sulfur / Q000378:metabolism*; D002648:Child; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006130:Growth Disorders / Q000209:etiology*; D006801:Humans; D007410:Intestinal Diseases / Q000150:complications / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D018384:Oxidative Stress; D011204:Poverty Areas; D012499:Sanitation
chemical_list: D000603:Amino Acids, Sulfur; D008715:Methionine; D003541:Cystathionine beta-Synthase