Jejunal Perfusion of Simple and Conjugated Folates in Tropical Sprue

Corcino, José J.; Reisenauer, Ann; Halsted, Charles H.

doi:10.1172/jci108472

Cited by 33 publications

(12 citation statements)

References 27 publications

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“…These in cluded celiac [9] and tropical sprue [11], both dis eases affecting the small intestine and associated with folate deficiency, and ulcerative colitis [12], an in flammatory disease that excludes the small intestine. Infusion solutions consisted of equimolar concentra tions of separately labeled 3 H-PteGlu and 14 C-PteGlu 7 (0.75 μΜ in tropical sprue and 2 μΜ in all other studies) in isotonic saline, pH 7.0, with polyethylene glycol as a nonabsorbable marker.…”

Section: Intestinal Absorption Of Dietary Folatesmentioning

confidence: 99%

The intestinal absorption of dietary folates in health and disease.

1989

Journal of the American College of Nutrition

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Dietary folates exist as pteroylpolyglutamates (PteGlun) that undergo hydrolysis to pteroylmonoglutamate (PteGlu) forms during the process of intestinal absorption. Using the technique of jejunal perfusion of separately labeled folates, our laboratory has demonstrated that hydrolysis of PteGlun occurs on the surface of the jejunum and is a prerequisite for folate absorption. An intestinal brush border pteroylpolyglutamate hydrolase (BB-PPH) has been identified in human and pig jejunum with characteristics that are distinct from those of an intracellular hydrolase (IC-PPH). Functional parallels of BB-PPH with in vivo hydrolysis of PteGlun in human and pig intestine and the clinical responsiveness of BB-PPH to different disease states indicate that this enzyme plays the major physiological role in folate absorption. Folate malabsorption is found in diseases which affect the jejunal mucosa and in response to various drugs. In most of these clinical conditions, folate malabsorption results from suppression of both of the processes of hydrolysis of PteGlun and jejunal uptake of PteGlu. Ongoing studies in miniature pigs are aimed at definition of the sequence of development of folate malabsorption in chronic alcoholism.

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Section: Intestinal Absorption Of Dietary Folatesmentioning

confidence: 99%

The intestinal absorption of dietary folates in health and disease.

1989

Journal of the American College of Nutrition

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“…This is demonstrated by the variety of clinical abnormalities that result from folate deficiency (e.g., megaloblastic anemia, growth retardation, and neurological disorders) (7,15,17,26) and by the health benefits attained by optimizing folate body homeostasis [e.g., prevention of neural tube defects and omphalocele and reduction in the risk of cardiovascular disease, colorectal cancer, stroke, and Alzheimer disease (3,8,9,13,18,24,41)]. Folate deficiency is prevalent in underdeveloped countries, and in the Western Hemisphere it often occurs as a result of impairment in intestinal absorption due to intestinal diseases (e.g., inflammatory bowl disease and celiac disease), drug interactions, and chronic alcohol intake (11,19,20,28,50). Folate deficiency has also been reported recently in hereditary folate malabsorption syndrome, a condition believed to be due to a defect(s) in the intestinal folate absorption process (35,49).…”

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confidence: 99%

Differentiation-dependent regulation of the intestinal folate uptake process: studies with Caco-2 cells and native mouse intestine

Subramanian¹,

Reidling²,

Said³

2008

American Journal of Physiology-Cell Physiology

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Subramanian VS, Reidling JC, Said HM. Differentiationdependent regulation of the intestinal folate uptake process: studies with Caco-2 cells and native mouse intestine. Am J Physiol Cell Physiol 295: C828 -C835, 2008. First published July 23, 2008 doi:10.1152/ajpcell.00249.2008.-Differentiation of intestinal epithelial cells is accompanied by alterations in levels of expression of many genes, including those involved in nutrient uptake. Effects of differentiation of intestinal epithelial cells on the physiological and molecular parameters of the intestinal folate uptake process are not well characterized. To address this issue, we used two models, Caco-2 cells and native mouse intestine. Studies with Caco-2 cells showed a significant increase in the initial rate of carrier-mediated folic acid uptake during differentiation (i.e., as the cells transitioned from preconfluent to confluent and then to postconfluent stages). This increase was associated with an increase in the level of expression of the human reduced folate carrier (hRFC) and the human protoncoupled folate transporter (hPCFT) both at the protein and mRNA levels with differentiation; it was also associated with a significant increase in activity of the hRFC and hPCFT promoters. Studies with native mouse intestine showed a significantly higher folate uptake in villus compared with crypt cells, which was again associated with a significantly higher level of expression of the mouse RFC and PCFT at the protein and mRNA levels. Together, these studies demonstrate that the intestinal folate uptake process undergoes differentiationdependent regulation and that this regulation is mediated via changes in the level of expression of both the RFC and PCFT. In addition, the studies suggest the possible involvement (at least in part) of a transcriptional mechanism(s) in this type of regulation of the intestinal folate uptake process. transport; epithelial transport; reduced folate carrier; proton-coupled folate transporter FOLATE IS ESSENTIAL FOR NORMAL cellular proliferation, growth, and functions. The coenzyme derivatives of folic acid are required for the synthesis of precursors of DNA and RNA and the metabolism of several amino acids including homocysteine (6,21,26,42). An adequate supply of folate is therefore necessary for normal human health and well-being. This is demonstrated by the variety of clinical abnormalities that result from folate deficiency (e.g., megaloblastic anemia, growth retardation, and neurological disorders) (7,15,17,26) and by the health benefits attained by optimizing folate body homeostasis [e.g

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“…Despite this evidence, aspiration of intestinal contents after perfusion of radiolabeled polyglutamates indicates the accumulation in the intestinal lumen of the products of hydrolysis (Halsted et at., 1975), which suggests that there may be backdiffusion of monoglutamates after intracellular hydrolysis. The suggestion that conjugase may act at the brush border in a manner similar to disaccharidases (Halsted et at., 1975), consistent with the presence of a brush-border binder for folates (Leslie and Rowe, 1972), has been largely, but not totally, excluded by the above-mentioned data and by the finding that mucosal activity of folate conjugase is not affected by tropical sprue in parallel to decreased disaccharidase enzyme activity at the surface of the cell (Corcino et at., 1976).…”

Section: Hydrolysis Of Polyglutamatementioning

confidence: 97%

“…However, no case of this enzyme deficiency has been documented. In inborn errors of metabolism attributed to congenital folate malabsorption, the defect appeared to affect monoglutamates and polyglutamates equally (Lanzkowsky et at., 1969;Santiago-Borrero et at., 1973), and in acquired malabsorption caused by tropical sprue, as well as in celiac disease, folate conjugase activity of jejunal biopsies is normal or increased, and polyglutamate malabsorption is no greater than that of monoglutamate Corcino et at., 1976;Halsted et at., 1976a). (See note added in proof, p.…”

Section: Hydrolysis Of Polyglutamatementioning

confidence: 99%

“…Although folate deficiency in tropical sprue has long been attributed to malabsorption, the latter could not be consistently demonstrated with physiologic doses until independent studies demonstrated that malabsorption of these doses was only detectable in the presence of glucose or galactose (Gerson et al, 1974;Corcino et al, 1975Corcino et al, , 1976. The extensive list of gastrointestinal and systemic diseases previously known to be associated with folate malabsorption has been enlarged by evidence that this may occur in cardiac failure (Hyde and Loehry, 1968), dermatitis herpetiformis , and systemic bacterial infections (Cook et al, 1974).…”

Section: Mucosal Transportmentioning

confidence: 99%

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