Inherited Defects of Vitamin B Metabolism

Cooper, Bernard A.; Rosenblatt, David S.

doi:10.1146/annurev.nu.07.070187.001451

Cited by 120 publications

(34 citation statements)

References 32 publications

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“…However, it is not known whether TC II like IF in some species (28) is secreted from the pancreas and mediate luminal uptake of Cbl via TC II-R. 2) patients with inherited disorders (29,30) of IF or IFCR develop Cbl deficiency, suggesting that IF/IFCR-mediated Cbl transport system is the only physiologically operational intestinal uptake system for Cbl transport in man. Despite its lack of importance in the normal uptake of dietary Cbl, it is possible that apical TC II-R can mediate uptake of TC II-Cbl when presented orally, particularly in patients who malabsorb Cbl due to several inherited disorders (29,30) or to surgical procedures such as gastrectomy and ileal resection (31). A child who malabsorbed Cbl due to inherited TC II deficiency responded well in Schilling test (32) (which measures Cbl absorption) when the child was orally fed with Cbl complexed to TC II.…”

Section: Discussionmentioning

confidence: 99%

Bipolar Functional Expression of Transcobalamin II Receptor in Human Intestinal Epithelial Caco-2 Cells

Bose¹,

Seetharam

Dahms³

et al. 1997

Journal of Biological Chemistry

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The plasma transport of cobalamin (Cbl 1 ; vitamin B 12 ) to all tissues/cells occurs bound to a plasma transporter, transcobalamin II (TC II), by receptor-mediated endocytosis (1) via transcobalamin II receptor (TC II-R). Recent studies (2) have shown that TC II-R is expressed as a non-covalent homodimer of molecular mass of 124 kDa in all human (2), rat (3), and rabbit (4) tissue plasma membranes. The plasma membrane expression of TC II-R is important for the tissue/cellular uptake of Cbl, since its functional inactivation in vivo by its circulatory antiserum causes intracellular deficiency of Cbl, which in turn results in the development of Cbl deficiency of the animal as a whole (4). Although TC II-R is expressed in the plasma membrane of all cells, its polarity of expression in epithelial cells is not known. Recent immunoblot studies (3) have revealed that in the rat kidney, TC II-R protein is expressed in both the isolated apical and basolateral membranes with an enrichment in the basolateral membranes by about 8-fold. However, how TC II-Cbl internalized via the TC II-R from either the apical or basolateral surface is processed is not known. Recent TC II-[ 57 Co]Cbl uptake studies (4) using filter-grown polarized Caco-2 cells have shown that [ 57 Co]Cbl taken up from the basolateral side in these cells was utilized as Cbl coenzymes, suggesting that these cells derive Cbl essential for their use from the basolateral side.Despite these studies, the details of intracellular sorting of Cbl and TC II by a polarized epithelial cell are poorly understood. The present studies were undertaken to address the issues related to polarized expression and function of TC II-R in human intestinally derived Caco-2 cells, a well established cell model used extensively to study nutrient transport and general intestinal epithelial cell biology (5, 6).The results of this study show that TC II-R is asymmetrically expressed in the ratio of 1:7 and 1:6.8 in the apical and the basolateral membranes of human intestinal mucosa and intestinally derived Caco-2 cells, respectively. Furthermore, when TC II-Cbl is presented on the apical side of Caco-2 cells or to the intestinal lumen of rats, TC II is transcytosed across the epithelial cell by a non-lysosomal pathway. In addition, these studies also demonstrate that when presented on the basolateral side, TC II is processed via the lysosomal pathway, resulting in the degradation of TC II and the utilization of intracellularly released Cbl as coenzymes.

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Section: Discussionmentioning

confidence: 99%

Bipolar Functional Expression of Transcobalamin II Receptor in Human Intestinal Epithelial Caco-2 Cells

Bose¹,

Seetharam

Dahms³

et al. 1997

Journal of Biological Chemistry

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“…In contrast, no known autoimmune disorders leading to defective plasma transport of Cbl involving functional loss of either transcobalamin II or its cell surface receptor has been reported to date. However, inherited disorders involving lack or defective expression of transcobalamin II are known (9), and these children generally develop Cbl deficiency faster than those with absorption defects (4). Thus, the consequence of defective uptake of plasma TC II-Cbl due to functional loss of TC II-R should also result in the faster development of Cbl deficiency, since TC II-R-mediated uptake of TC II-Cbl is the only mode of delivery of physiological amounts of Cbl to all the tissues (10).…”

mentioning

confidence: 99%

In Vitro and in Vivo Inactivation of Transcobalamin II Receptor by Its Antiserum

Bose

Komorowski

Seetharam

et al. 1996

Journal of Biological Chemistry

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“…Increased levels of plasma TC II have been reported in patients with a variety of diseases (3), indicating that the TC II gene may have a basal expression in many cells, but could be induced under some pathological conditions. Lack of expression or expression of defective forms of TC II leads to the development of intracellular cobalamin deficiency (4). Recent studies (2,5,6) from our laboratory have shown that in the most common form of TC II deficiency, lack of immunoreactive plasma TC II is due to lack of TC II protein synthesis, which in turn is due to extremely low levels of TC II mRNA (2).…”

Section: Human Transcobalamin II (Tc Ii)mentioning

confidence: 99%