Molybdenum, Tungsten, Vanadium, and Chromium - Biological Inorganic Chemistry - page 340

FIGURE 17.18 Model of the pathway for reduction and accumulation of vanadium in ascidian vanadocytes. (From Michibata, Yamaguchi,

Uyama, & Ueki, 2003 . Copyright 2003 with permission from Elsevier.)

via the transferrin/transferrin receptor pathway (although how they dissociate from the receptor inside the cell
remains unclear). They may also influence the redox balance of cells, interacting with the glutathione system.
However, despite their potential beneficial effects, failure to bring the use of vanadium salts into therapeutic
practice is due on the one hand to their toxicity, and on the other to their limited window of therapeutic action e

while they may target some parts of the complex insulin signalling cascade, they cannot exert the exquisite
specificity of the natural hormone both to activate, and to ensure the extinction of its activation cascade once its
objectives have been achieved.

Chromium
As was pointed out in Chapter 1, chromium has become immensely popular as a nutritional supplement, for
promotion of muscle development, and as a weight-loss agent ( Vincent, 2003, 2004) , second only to calcium as
a mineral supplement ( Nielsen, 1996 ) . However, while there are indications that Cr administration may be useful
as an adjuvant therapy in type 2 diabetes as well as in the regulation of diabetes during pregnancy, the precise
biochemical mode of action of chromium remains unclear (Lau et al., 2008). The biologically relevant form, the
trivalent Cr 3 þ ion, seems to be required for proper carbohydrate and lipid metabolism in mammals. However,
chromium deficiency is difficult to achieve. It has recently been reported that a diet with as little Cr as was
reasonably possible to achieve had no effect on body composition, glucose metabolism, or insulin, when compared
to a Cr “sufficient” diet. The authors, who include the principal protagonist of Cr essentiality over the last decade,
conclude that, 'together with the results of other recent studies these results clearly indicate that chromium can no
longer be considered an essential element' ( Di Bona, 2011 ) .
No Cr-dependent enzymes or Cr-binding proteins have been identified to date. However, one chromium-
binding peptide, chromodulin, with the putative sequence pEEEEGDD (where pE is pyroglutamate) has been
characterised ( Chen, Watson, Gao, Sinha, Cassady, & Vincent, 2011 ), and found to bind 4 chromic ions per
peptide. It is proposed that the chromium-loaded chromodulin may function in the amplification system for insulin
signalling ( Vincent, 2000b ) for transporting Cr 3 þ to tissues in an insulin-responsive manner.
While there are obvious similarities between both the name, and the proposed mechanism of action of
chromodulin and the Ca 2 þ -binding protein calmodulin, much remains to be done to establish unequivocally the
mechanism of chromodulin action at the molecular level, and I personally remain extremely sceptical regarding
the reputedly magical properties of dietary supplementation with chromium.