Cobalt enzyme-like activity

After Werner s death in 1919, there was little activity in the field of stereochemistry of coordination compounds. An exception is found in the work of Yuji Shibata, who had been one of Werner s students, and who continued with excellent stereochemical work when he returned to Japan. His work on the enzyme-like activity of cobalt complexes furnishes especially interesting examples of stereoselectivity and of the catalytic action of such compounds (6). T. P. McCutcheon and V. L. King, Americans who had done their theses on stereochemical topics under Werner s guidance, did not continue in that field. King, who actually performed the first resolution of an asymmetric complex ( 7), went into industrial work. McCutcheon became a member of the faculty at the University of Pennsylvania and did research on complex compounds, but not on their stereochemistry. 

Cobalt most often depresses the activity of enzyme including catalase, amino levulinic acid synthetase, and P-450, enzymes involved in cellular respiration. The Krebs citric acid cycle can be blocked by cobalt resulting in the inhibition of cellular energy production. Cobalt can replace zinc in a number of zinc-required enzymes like alcohol dehydrogenase. Cobalt can also enhance the kinetics of some enzymes such as heme oxidase in the liver. Cobalt interferes with and depresses iodine metabolism resulting in reduced thyroid activity. Reduced thyroid activity can lead to goiter. 

If we are correct in assuming that the unusual active site cobalt spectrum reflects a geometry about the metal atom which in some way is advantageous for catalytic activity, conditions which alter activity of the enzyme should be paralleled by alterations of the spectra. This can be tested by comparison of the pH dependence of the cobalt spectra with that of enzymic activity (Figure 7). Like the zinc enzyme, the activity... 

If our postulates are correct the most interesting feature of P-450 is the manner in which the protein has adjusted the coordination geometry of the iron and then provided near-neighbour reactive groups to take advantage of the activation generated by the curious coordination. Vallee and Williams (68) have observed this situation in zinc, copper and iron enzymes and referred to it as an entatic state of the protein. It is also apparent that some such adjustment of the coordination of cobalt occurs in the vitamin B12 dependent enzymes. As a final example we have looked at the absorption spectra of chlorophyll for its spectrum is in many respects very like that of a metal-porphyrin. This last note is intended to stress the features of chlorophyll chemistry which parallel those of P-450. 

---