Cobalt biological function

In contrast to iron and copper, which dominate the scene of transition metal biochemistry and are components of a variety of metalloproteins, cobalt occupies a relatively modest niche in biology. A biological function of cobalt can only be said to have been established at the molecular level in a few cases involving coninoid coenzymes (7). 

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). 

The behavior of metals as atoms or ions deeply affects the electrochemical reactions they undergo, and similarly affects the metabolism of plants and animals. Iron, copper, cobalt, potassium, and sodium are examples of metals that are essential to biological function. Some metals such as cadmium, mercury, lead, barium, chromium, and beryllium are highly toxic. 

The accompanying table lists the essential elements in the human body. Of special interest are the trace elements, such as iron (Fe), copper (Cu), zinc (Zn), iodine (I), and cobalt (Co), which together make up about one percent of the body s mass. These elements are necessary for biological functions such as growth, transport of oxygen for metabolism, and defense against disease. There is a delicate balance in the amounts of these elements in our bodies. Too much or too little over an extended period of time can lead to serious illness, retardation, or even death. 

Cob(III)alamins undergo ligand exchange reactions typical of cobalt(III) complexes, most of which are not directly relevant to biological function. One-electron reduction to cob(II)alamin and two-electron reduction to cob(I)alamin are biologically relevant. The standard reduction potentials are +200 and —610 mV, respectively, for the base-on Cob(III)/Cob(II) and Cob(II)/Cob(I) couples, referenced to the normal hydrogen electrode. ... 

Vitamin B12.24 The best known biological function of cobalt is its intimate involvement in the coenzymes related to vitamin Bl2, the basic structure of which is shown in Fig. 25-F-6. The macrocyclic ring is the corrin system it is reminiscent of the porphyrin system, the most notable difference being the absence of a methine (CH) bridge between one pair of pyrrole rings. 

Preparations are listed in Table 47. Main interest lies in determining how metal ions catalyze the hydrolysis of ADP and ATP. ATP plays a crucial role in the energy metabolism of all living cells and divalent metal ions (Mg +, Mn " and Ca ) play an important role in these phosphoryl transfer processes. Divalent metal ions such as Mg +, Ca, Zn, Cu and Mn " provide only modest in vitro catalysis "" and stronger, more specific coordination to phosphate units appears to be required by the enzyme. Co " (and Cr" ) complexes of ADP and ATP have been shown to mimic many of the biological functions of the Mg" enzyme, and since the cobalt(III)-phosphatc coordination remains intact, the specificity of alternative coordination sites, and the stereochemical requirements at phosphorus, have been elucidated in some cases. Often the Co "-enzyme species is biologically active and several enzymic functions of ATP have been examined in this manner. 

Transition elements have some biological functions for chemistry of living systems. Metals, such as iron, cobalt, copper, and molybdenum have functions in living systems, whereas protein contains iron, which helps in electron transfer and oxygen transport. Most transition metal elements plays similar major roles in various biological living systems and for these reasons we focused on the transition metals. 

Figure 23 Variation of RBE as a function of depth in the carbon-ion beam used for clinical applications at HIMAC, Chiba, Japan (carbon-12, 290 MeV/u, SOBP 60 mm). The biological system is the well-codified intestinal crypt regeneration in mice. The selected criterion is 20 regenerating crypts per circumference after a single fraction irradiation. RBE determinations were performed at the beginning, middle, and end of the SOBP and at the level of the initial plateau. The dose-effect relationship for cobalt-60 is indicated for comparison. An estimation of the LET is presented for each depth where biological determinations were made. (From Gueulette, unpublished.)...

Determine whether or not the I) value for the biological indicator varies as a function of the dose rate. With cobalt-60, dose rate differences are not of much concern (variance of 0.1-0.5 Mrad/hr), whereas electron beam sterilization might produce dose rate variances of several Mrads per min ... 

The very important role of the heme system, Fe(Proto)LL ( 3) in biological oxygen transport and consumption as well as electron transport is a main topic not only of biochemists, but of bioinorganic chemists and biomimetic chemists as well for this general topic, the reader may consult some recent review articles [14-21,22]. Bioinorganic chemists have studied the effect of replacement of iron by other 3d metals, especially chromium, manganese, and cobalt, and frequently, interesting structural, spectral, or functional models [14,20] of the heme enzymes have been found with these metals. 

Vitamin B12 is a biologically active corrinoid, a group of cobalt-containing compounds with macrocyclic pyrrol rings. Vitamin B12 functions as a cofactor for two enzymes, methionine synthase and L-methylmalonyl coenzyme A (CoA) mutase. Methionine synthase requires methylcobalamin for the methyl transfer from methyltetrahydrofolate to homocysteine to form methionine tetrahy-drofolate. L-methylmalonyl-CoA mutase requires adenosylcobalamin to convert L-methylmalonyl-CoA to succinyl-CoA in an isomerization reaction. An inadequate supply of vitamin B12 results in neuropathy, megaloblastic anemia, and gastrointestinal symptoms (Baik and Russell, 1999). 

Foster, M. A. et al. Cobalt as a Functional Group, in Chemical Reactivity and Biological Role of Functional Groups in Enzymes, (ed. Smellie, R. M. S.) Academic Press, New York 1970, p. 187... 

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