Kidneys and cobalamin (B12):
The information goes back decades, although researchers still are trying to better understand the connection between kidneys and cobalamin. This is one of the issues about which mostly questions remain.
http://www.metabolismjournal.com/art...00661/abstract
This is very interesting. Maybe one of our more brilliant members can shed some light.
From:
Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B12
Quote:
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Megalin is important for normal uptake of filtered TC-B12 and accumulation of the vitamin. In megalin-deficient mice, increased urinary excretion of both TC (Fig. 2) and vitamin B12 (Table 1) was observed. Urinary B12 concentration was increased approximately fourfold despite significant lower serum B12 levels. As a result, urinary B12 clearance was increased ~28-fold in megalin-deficient mice. Furthermore, no vitamin B12 could be identified by immunocytochemistry in the proximal tubules from megalin-knockout mice, indicating defective cellular uptake of the vitamin (Fig. 3). Little or no TC was identified in urine from control littermates (Fig. 2), whereas cellular B12 uptake was evident in proximal tubules (Fig. 3). The defect in vitamin accumulation in megalin-deficient mice was further substantiated by the determination of vitamin B12 concentration in kidney cortical tissue from two megalin-knockout mice, showing a fourfold reduction compared with normal controls (Table 1).
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From:
http://ndt.oxfordjournals.org/cgi/co...ull/17/11/1867
Quote:
Cubilin
Cubilin is a 460-kDa peripheral membrane protein, previously referred to as gp280, and identical to the intrinsic factor-vitamin B12 receptor known from the small intestine. Its primary sequence, determined in rat [5], man [6] and canine [7], is conserved with an overall homology of 69% between rat and human cubilin and 83% between canine and human cubilin. Its structure consists of a 110 amino acid N-terminal stretch, followed by eight EGF and 27 CUB (Complement C1r/C1s, Uegf and Bone morphogenic protein-1 [8]) domains. Each CUB domain consists of 110 amino acids. The structure of CUB domains, which has been determined on spermadhesins [9] (a family of sperm proteins which consist of a single CUB domain), is characterized by two layers of five anti-parallel ß-sheets connected by ß-turns which include the least conserved regions and likely ligand-binding sites. Interestingly enough, a single spermadhesin can bind simultaneously two distinct ligands. The CUB domains can form dimers by piling up via the ß-sheets, in a manner that may favour the exposition of ß-turns to the surface. Therefore, the least conserved regions of the ß-turns will be preferentially exposed and available for interaction with ligands. This accumulation of CUB domains suggests that cubilin may interact with a variety of ligands.
Cubilin is a peripheral protein and its membrane association depends on the 110 amino acids at the N-terminus stretch [10] and may involve a putative amphipathic helix as well as palmitoylation. Biochemical and immuno-morphological data suggest that the internalization of cubilin is, at least in part, carried out by megalin [5,11].
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Sure is some fascinating newer stuff to read! I'm not saying any of this is your problem, just providing some of the interesting literature that has been coming out as a result of more attention being paid to the kidney/B12 connection.
rose