Cadmium -substituted carbonic anhydrase

It should be noted that activity of cadmium-substituted carbonic anhydrase may be enhanced at higher pH values (ca. pH 9). See Ref. (182b) and Bauer, R. Limkilde, P. Johansen, J. T. Biochemistry 1976,15, 334. 

The X-ray structure of the unsubstituted tris(pyrazolyl)borato zinc nitrate has been solved showing a unidentate coordination mode for nitrate, in contrast with the t-butyl substituted ligand, which shows anisobidentate nitrate coordination due to the steric effects.232 A partial explanation of the reduced activity of cadmium-substituted carbonic anhydrase is offered by Parkin on the basis of the comparison of nitrate coordination to cadmium and zinc trispyrazo-lylborate moieties. A contributing factor may be the bidentate coordination supported by the cadmium that does not allow the facile access to a unidentate bicarbonate intermediate, which could be highly important to carbonic anhydrase activity.233... 

Nickel is required by plants when urea is the source of nitrogen (Price and Morel, 1991). Bicarbonate uptake by cells may be limited by Zn as HCOT transport involves the zinc metal-loenzyme carbonic anhydrase (Morel et al., 1994). Cadmium is not known to be required by organisms but because it can substitute for Zn in some metalloenzymes it can promote the growth of Zn-limited phytoplankton (Price and Morel, 1990). Cobalt can also substitute for Zn but less efficiently than Cd. 

Substitution of foreign metals for the metals in metalloenzymes (those that contain metals as part of their structures) is an important mode of toxic action by metals. A common mechanism for cadmium toxicity is the substitution of this metal for zinc, a metal that is present in many metalloenzymes. This substitution occurs readily because of the chemical similarities between the two metals (for example, Cd2+ and Zn2+ behave alike in solution). Despite their chemical similarities, however, cadmium does not fulfill the biochemical function of zinc and a toxic effect results. Some enzymes that are affected adversely by the substitution of cadmium for zinc are adenosine triphosphate, alcohol dehydrogenase, and carbonic anhydrase. 

Cadmium is generally considered to be toxic to organisms and how the marine phytoplankton utilize their cadmium is unknown. Cadmium may substitute for zinc in carbonic anhydrase at times when zinc is limiting (Price and Morel, 1990 Lane and Morel, 2000). It is possible that cadmium may play a role in polyphosphate bodies, a form of cellular storage of phosphorus that has been shown to contain significant quantities of elements such as calcium, zinc, and magnesium (Ruiz et al, 2001). 

It appears that cobalt plays a particularly important role in the growth of cyanobacteria (Saito et al, 2002 Sunda and Huntsman, 1995b). Both Prochlorococcus and Synechococcus show an absolute cobalt requirement that zinc cannot substitute for (Figure 18(a)). The growth rate of Synechococcus is little affected by low zinc concentrations, except in the presence of cadmium which then becomes extremely toxic (Saito et al, personal communication). The biochemical processes responsible for the major cellular utilization of zinc and cobalt in marine cyanobacteria are unknown, however. These metals may be involved in carbonic anhydrase and/or other hydrolytic enzymes. Cobalamin (vitamin B12) synthesis is a function of cobalt in these organisms, yet B12 quotas tend to be very small (on the order of only 0.01 p.mol (mol C) ) and hence are not likely represent a significant portion of the cellular cobalt (Wilhelm and Trick, 1995). 

What are the essential chemical properties provided by zinc and its ligands in carbonic anhydrase (It may be noted that replacement of zinc by cobalt and cadmium has been carried out and for the cobalt substitution there is no change in properties while... 

Enzymes having metals as their components can also be inhibited by a substitution of one of these metal ions by another ion with the same charge and a similar size. For example, the toxic effect of cadmium is due to a substitution for zinc, which is a common component in metalloenzymes. The Zn " " and Cd ions are chemically similar, however, the cadmium-containing enzyme does not function properly. The Cd " ions can result, for instance, in the inhibition of amylase, adenosine triphosphatase, adcohol dehydrogenase, glutamic-oxalacetic transaminase, carbonic anhydrase and peptidase activity in carboxypeptidase [4]. 

Cadmium is a toxic element (see Chapters 1,14,15) that accumulates especially in kidney and liver [4] being bound preferably to metallothionein (Chapters 6,11). On the other hand, the chemical similarity of Cd " " to Zn " is confirmed by the fact that carbonic anhydrase of marine phytoplankton contains Cd (Chapter 16), whereas the corresponding zinc enzymes are found in organisms from aU kingdoms [5] catalyzing the reversible hydration of carbon dioxide. In marine diatoms cadmium, cobalt, and zinc can functionally substitute for one another to maintain optimal growth [6]. Cadmium-carbonic anhydrase is involved in the acquisition of inorganic carbon for photosynthesis [6]. 

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