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380 G. GAŁUSZKA, M. CIEŚLAK-GOLONKA

ABSTRACT

Chromium was discovered in 1797 by Louis Nicolas Vauqelin, a French chemist. The element has valences that rangę from (—2) to (+6). Under environ-mental conditions chromium in compounds exists in the trivalent and hexava-lent State [1]. Chromium was recognized as an essential tracę element in 1959 [28]. The essentiality of Cr(III) was established examining rats fed a Torula yeast diet which proved to be Cr-deficient. Rats developed glucose intolerance which could be reversed only by addition of Cr(III) to the diet. Chromium defi-ciency in humans results in symptoms comparable to those associated with diabetes and cardio-vascular diseases [16]. The Cr(III) complex potentiating the insulin action was called GTF (glucose tolerance factor). The yeast GTF has been found to be a Iow molecular weight molecule comprised of Cr(III), nicotinic acid, glycine, glutamic acid and cysteinę. Among the several possible mechanisms by which GTF might act, in vivo and in vitro results suggest that the most likely mechanism is a direct enhancement of the insulin activity via facilitating its bonding to cellular receptors [29]. As Cr(III) was recognized as an essential element, dietary intake has been found to rangę from 13 to 56 pg [40]. However, in contrast to Cr(VI) it is still unanswered question on the level of Cr(III) toxicity [40]. Studies of Cr(III) cellular uptake have determined that much of the intracelłular Cr(III) is associated with the nucleus. It has also been shown that Cr(III)-based supplements like Cr(III) picolinate can cause chromo-some aberrations in human lymphocytes (Tab. 1). The bioinorganic chemistry of Cr(III) ion is based on investigation of numerous Cr(III) complexes with ligands of biological relevance [1], With few exceptions, they are six coordinate with the main characteristic of relative kinetic inertness in aqueous Solutions. This, for example, rules out the possibility of chromium presence in the enzyme activity centre. Being a hard Lewis acid chromium(III) has an affinity towards oxygen and nitrogen donor ligands. There are several monomeric and dimeric species which may serve as models for GTF (Tab. 2, Fig. 4). As for over 30 years the investigators tried to isolate GTF without success, the view of non-essentiality of this ion received morę support [10, 32, 36]. Recently, a candidate for the biologically active form of chromium, Iow molecular weight substance (LMWCr) has been isolated by Yamamoto et al. [69]. LMWCr is an oligopeptide with the molecular weight approximately 1500 which binds 4 chromium ions per molecule [Tab. 3], The oligopeptide comprises of glycine, cysteinę, glutamate and aspartate. Among various model compounds (Fig. 4) the trimer [Cr30(0₂CCH2CH3)₆(H₂0)3] was found to be active and was pro-posed for a treatment for adult-onset diabetes [73],

In conclusion, it appears very likely that four decades of intensive research on biological chromium resulted in finding the answer to the question on the essentiality of this element. The “new GTF”, i.e. the active chromium containing species, primarily functions as the activator of insulinę receptors whereas the “old GTF” may serve rather as a readily absorbed chromium dietary supplement.