Postnatal ontogeny of intestinal GCPII and the RFC in pig

Abstract

In humans and pigs, hydrolysis of dietary polyglutamyl folates is carried out by intestinal brush border folate hydrolase [glutamate carboxypeptidase II (GCPII)], whereas the transport of the monoglutamyl folate derivatives occurs via the intestinal brush border reduced folate carrier (RFC). The study objective was to measure the expression of intestinal GCPII and RFC during postnatal development of pigs and their effects on plasma and liver folate concentrations. Duodenum, jejunum, ileum, liver, and plasma samples were collected from female Yorkshire pigs at birth, 24 h, 1 wk, 3 wk, and 6 mo (n=6 at each time point). GCPII mRNA transcripts and protein (normalized using beta-actin), and enzyme activity (normalized per mg mucosal protein) were highest in all segments of small intestine at birth and were undetectable in ileum after 1 wk, whereas jejunal protein and activity predominated at 6 mo. RFC mRNA transcripts were present in all segments of small intestine at birth and declined significantly throughout development to 6 mo. Conversely, RFC protein increased twofold during the first 24 h and remained constant throughout development in all segments of small intestine. Liver RFC mRNA transcripts were detected at birth but were reduced by 6 mo. Liver folate concentration increased throughout postnatal development, whereas plasma folate levels increased during the first 24 h but decreased over time, reflecting the pattern of RFC expression in small intestine. These findings show that intestinal GCPII and intestinal and hepatic RFC all exhibit ontogenic changes in the pig that are reflected in postnatal folate status.

Dietary Arachidonate Differentially Alters Desaturase-Elongase Pathway Flux and Gene Expression in Liver and Intestine of Suckling Pigs,

“…In addition, liver mRNA abundance of FADS2, ELOVL5, and FADS1 precipitously dropped from d 0 to 4 and did not recover to the initial d 0 values throughout the first 16 d of life. These results are congruent with literature reports showing, first, that FADS2 and FADS1 increase in liver throughout gestation (27) and second, that many genes with metabolic involvement in pigs show a similar pattern of rapid decline following birth and rebound several weeks later (28,29). In fact, Clandinin et al (30) demonstrated developmental increases in the ability of pig fetuses to synthesize trienes, tetraenes, and penteanes from preterm (60 d gestation) to full-term.…”

Dietary Oligosaccharides Increase Colonic Weight and the Amount but Not Concentration of Bacterially Synthesized Folate in the Colon of Piglets

“…Despite the fact that piglets were fed the NRC-recommended amount of folate, they had very low RBC folate concentrations and high homocysteine concentrations, characteristic of suboptimal folate status in humans. These concentrations, however, were similar to those reported in the literature for piglets (23,(60)(61)(62). A high plasma homocysteine concentration in piglets is thought to be due to their very rapid rate of growth, which creates a high demand for S-adenosylmethionine (product of a reaction between methionine and the enzyme methionine adenosyltransferase), which serves as a universal carbon donor in the body and specifically for creatine synthesis (63).…”

“…Hydrolysis of the polyglutamyl form of folate (mainly from diet) occurs primarily in the brush border of the proximal small intestine in humans and pigs by glutamate carboxypeptidase II (GCPII) (23,54). Very little is known about the regulation of GCPII in the distal bowel (23).…”

“…Piglets offer the advantage of smaller size and the relative ease of manipulating their microflora compared with adult animals. Unlike rats, pigs do not practice coprophagy and have a similar mechanism of folate absorption to humans (21)(22)(23)(24).…”

Post-hatching ontogeny of intestinal proton-coupled folate transporter and reduced folate carrier in broiler chickens

“…Higher expression of Slc19a1 transcripts was detected in suckling rats compared with weanling or adult animals (Balamurugan and Said, 2003). Shafizadeh and Halsted (2009) recently showed that Slc19a1 mRNA transcripts were present in the small intestine at birth and declined significantly throughout development to 6 months in pig. Balamurugan et al (2007) also found that there was a gradual decrease with development in the abundance of mRNA and protein of a specific folate transporter (encoded by folt-1 gene) in the intestine of nematodes.…”