Research article

The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes

Eleonore S Köhler¹ , Selvakumari Sankaranarayanan¹ , Christa J van Ginneken² , Paul van Dijk¹ , Jacqueline LM Vermeulen³ , Jan M Ruijter⁴ , Wouter H Lamers^1,3 and Elisabeth Bruder⁵

¹  Department of Anatomy & Embryology, Maastricht University, Maastricht, The Netherlands

²  Department of Veterinary Medicine, Veterinary Anatomy & Embryology, University of Antwerp, Belgium

³  AMC Liver Center Academic Medical Center, University of Amsterdam, The Netherlands

⁴  Department of Anatomy & Embryology, Academic Medical Center, University of Amsterdam, The Netherlands

⁵  Department of Pathology, Basel University Hospital, Basel, Switzerland

author email corresponding author email

BMC Developmental Biology 2008, 8:107doi:10.1186/1471-213X-8-107

Published:	10 November 2008

Abstract

Background

Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS), ornithine aminotransferase (OAT), argininosuccinate synthetase (ASS), arginase-1 (ARG1), arginase-2 (ARG2), and nitric-oxide synthase (NOS) were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens.

Results

Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2.

Conclusion

The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants.