Vanadium metabolism

It is particularly significant that the distribution of vanadium among tissues or subcel-lular fractions is independent of whether the oxidation state of the vanadium salt administered is +3, +4, or +5175,179. This result implies that all metabolic vanadium is converted to a common oxidation state in the circulation, probably to the V02+ ion, before being assimilated by most tissues, the kidney perhaps being an exception. 

Birnboim, H.C. (1988). A superoxide anion induced DNA strand-break metabolic pathway in human leukocytes effect of vanadium. Biochem. Cell. Biol. 66, 374-381. 

Chromium has proved effective in counteracting the deleterious effects of cadmium in rats and of vanadium in chickens. High mortality rates and testicular atrophy occurred in rats subjected to an intraperitoneal injection of cadmium salts however, pretreatment with chromium ameliorated these effects (Stacey et al. 1983). The Cr-Cd relationship is not simple. In some cases, cadmium is known to suppress adverse effects induced in Chinese hamster (Cricetus spp.) ovary cells by Cr (Shimada et al. 1998). In southwestern Sweden, there was an 80% decline in chromium burdens in liver of the moose (Alces alces) between 1982 and 1992 from 0.21 to 0.07 mg Cr/kg FW (Frank et al. 1994). During this same period in this locale, moose experienced an unknown disease caused by a secondary copper deficiency due to elevated molybdenum levels as well as chromium deficiency and trace element imbalance (Frank et al. 1994). In chickens (Gallus sp.), 10 mg/kg of dietary chromium counteracted adverse effects on albumin metabolism and egg shell quality induced by 10 mg/kg of vanadium salts (Jensen and Maurice 1980). Additional research on the beneficial aspects of chromium in living resources appears warranted, especially where the organism is subjected to complex mixtures containing chromium and other potentially toxic heavy metals. 

High levels of dietary tin increased zinc loss from rats (Greger 1989). Zinc prevented toxic effects of vanadium (10 mg/kg BW) on bone metabolism of weanling rats (Yamaguchi et al. 1989). 

Yamaguchi, M., H. Oishi, and Y. Suketa. 1989. Effect of vanadium on bone metabolism in weanling rats zinc prevents the toxic effect of vanadium. Res. Exper. Medic. 189 47-53. 

Vanadium. Vanadium is essential in rats and chicks. Estimated human intake is less than 4 mg/d. In animals, deliciency results in impaired growth, reproduction, and lipid metabolism, and altered thyroid peroxidase activities. Vanadium may play a role in the regulation of INaK)-ATPase. phosphoryl transferases, adenylate cyclase, and protein kinases. 

Vanadium 15 mg Lipid metabolism, regulation of cholesterol synthesis, ATPases Unknown Unknown... 

Each of these minerals participate in a variety of biologic functions and is necessary for normal metabolism. Other trace minerals essential to humans but for which deficiency states have not been recognized include nickel, vanadium, cobalt, and silicon (Table 66.2). 

Extrapolating from well-characterized enzymatic inhibition in test tubes, numerous mechanistic ideas concerning the in vivo effects of vanadium compounds have been advanced. The effects of vanadium compounds as transition-state analogs of certain enzymes with a phosphoprotein intermediate in their reaction scheme is proposed to account for the action of vanadium [11] in many biological systems. Unfortunately, it is often difficult to determine if the inhibition observed in the test tube occurs in vivo. For example, although vanadate is a potent inhibitor of plasma membrane ion pumps (such as the sodium potassium ATPase) in the test tube, it is difficult to determine if these pumps are actually inhibited in animals exposed to vanadium compounds. Currently, the role of vanadium compounds as protein phosphatase (PTP) inhibitors is believed to be related to the metabolic effects of this... 

Other forms of vanadium have been implicated in the stimulation of the plasma membrane vanadate-dependent NAD(P)H oxidation reaction. Decavanadate has been shown to be a more potent stimulator of the vanadate-dependent NADH oxidation activity than added orthovanadate [30,31], Interestingly, decavanadate reductase activity has been found to be an alternative activity of an NADP-specific isocitrate dehydrogenase [32], Diperoxovanadium derivatives have also been shown to be involved in this type of reaction [33,34], Decavanadate may play a role in the biological role of vanadium, as it is found in yeast cells growing in the presence of orthovanadate [8] and is a potent inhibitor of phosphofructokinase-1, the control step of glycolysis, and other metabolic reactions [35],... 

The role of these interesting plasma membrane-dependent, vanadate-stimulated NAD(P)H oxidation reactions in cellular metabolism remains to be elucidated, although multiple interactions with cellular metabolism and components are possible including interactions with xanthine oxidase and lipid peroxidation [24], Decavanadate has been shown to enhance cytochrome c reduction [31], and cytochrome c release from mitochondria is associated with initiation of apoptosis. Perhaps the reduced cytochrome c is more readily released from the mitochondria. With increasing emphasis on the redox properties of vanadium being important in its pharmacological effects, it is quite possible that these reactions, either protein dependent or not, may play a role in therapeutic actions of vanadium. 

Vanadium Compounds and Cellular Oxidation-Reduction Metabolism... 

Inhibition of Phosphate-Metabolizing Enzymes by Vanadium Compounds... 

Vanadium has effects similar to and different from that of insulin [100,101,124], The antidiabetic influence of the metal can be considered insulin-enhancing, rather than insulin-mimetic, because vanadium compounds cannot totally substitute for insulin in any model of diabetes that strictly requires insulin, such as the BB rat [125], a model of type 1 diabetes. In addition, vanadium can exert its antidiabetic effects via a mechanism or combination of mechanisms distinct from that of insulin. The metabolic actions of vanadium on metabolism do not include all of the actions of insulin, yet normal animals produce less serum insulin when given vanadium. The terms insulin-mimetic or insulin-like frequently appear in the literature for actions of vanadium that cannot be classified as similar to or different from that of insulin in the experimental system utilized. 

Specific vanadium-induced alterations in the activity or expression level of components of metabolic pathways are described here. Many of these changes are not caused by alterations in the pathway enzymes themselves but in enzymes and factors involved in regulation, commonly referred to as signal transduction systems. Section 11.3 will discuss the alterations described in this section in the context of general signal transduction processes affected by vanadium. 

As work with vanadium compounds and diabetes in cell system has continued, it has become clear that there are also insulin-independent mechanisms at work. One insulin-independent signal transduction pathway appears to be involved in glycogen metabolism reactions in rat adipocytes [137] that also involve PI-3K. A major difference was that only vanadate promoted glycogenesis through the activation of a cytosolic protein tyrosine kinase, which was mediated in an insulin receptor-independent manner. 

Simulation of glucose transport and glucose transporter translocation from intracellular stores to the plasma membrane in muscle cells by vanadate and peroxovan-adate involve a mechanism independent of PI-3K and protein kinase C systems utilized for stimulation of these processes by insulin. The transport of GLUT4 to the plasma membrane in muscle cells growing in culture after stimulation by vanadate, peroxovanadate, or insulin all require an intact actin network [138], Sometimes, the insulin-like action of vanadium is accompanied by overall stimulation of actual metabolic pathways. One example of this is the stimulation of the pentose phosphate pathway observed when vanadate promotes the incorporation of glucose into lipids, an antilipogenic effect [139],... 

The influences of vanadium compounds on cardiovascular function, a major complication of diabetes, has been reviewed [144], One of the first papers on the antidiabetic effects of oral administration of vanadium compounds (vanadyl sulfate) to rats with STZ-induced diabetes showed improvement of diabetes-impaired cardiac function [122], Recent work has focused on the correction of metabolic defects of diabetes by vanadium and learning more about the immediate mechanism of the antidiabetic effect. The assumption is made that amelioration of the basic metabolic problems of diabetes by vanadium or any other drug will alleviate the long-term complication arising from disease. Diet supplementation with minerals, such as chromium, appears to complement traditional treatments of diabetes to slow the development of complications. Mineral supplementation is believed to be most effective when dietary supplementation is used to correct a deficiency of a mineral [145],... 

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