Why Calcium? Principles and Applications in Bioinorganic Chemistry-IV Ei-lchiro Ochial Juniata College, Huntlngdon, PA 16652 Calciumis the fifthmost ahundant element (after C, H, 0, N) in the human body. Of the body calcium, 95%is hound in the hones and tooth enamel, hut i t is in dynamic equilibrium with the remaining pools of calcium. The remaining calcium is widely distributed throughout the hody in hody fluids and soft tissues. The importance of calcium to human health has long been recognized hut seems to have heen rediscovered as attested by recent popular publications and public interest (1).
The functions of the majority of Ca(I1) are structural, whether in hone. shells. or other hard tissues: Ca(I1) is also utilized to maintain the integrity of cell membranesand the cell10W M). This implies that there is a continuous influx of Ca(I1) into cytoplasm; this is partially due t o imperfect shielding of plasmamembrane against Ca(I1) invasion along the high concentration gradient. Thus, the time differential of [Ca(II)], may be expressed by:
The first term represents the passive inward leaking, and the second represents the active pumping. In the resting state, [Ca(II)], is kept low and constant, because the two terms are balanced. A chemical or electrical signal typically opens the gated Ca(I1) channels, momentarily making the leak term very large. This will lead to a very high [Ca(II)],, but then the k term would increase because the Ca(I1)ATPase is activated by Ca(I1). However, the pumping process would slightly lag behind the change in the leak term, because of its dependence on [Ca(II)]. Therefore, [Ca(II)], can transiently increase significantly, up to M (i.e., 100fold increase), but then the k process would reduce [Ca(II)], back to the resting value. Meanwhile the high [Ca(II)], would have exerted its effect as outlined above (see Fig. 2). The situation with cAMP is analogous, as outlined above for the action of epinephrine, in the aense that cAMP concentration rises and declines rapidly. The descri~tionabove indicates that several soecial characters are required for an SM.Important among them are: ( 1 ) its intracellular concentrationcan be altered rapidly, and Volume 68
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(2) it should be able t o exert its effect rapidly by binding to its effector. As far as binding strength is concerned, Ca(I1) is not particularly favorable. I t has a rather special affinity for carboxylate oxygen, hut its affinity is not significantly greater than those of other ubiquitous cations such as Mg(I1) or Zn(I1). These latter cations, however, have more affinity toward nitroeen lieands. If one of these cations had been , would have developed effectors chosen for a & ~ organisms which contain nitroeen lieands. The only advantage of Ca(I1) in this respectseemi to be that acidic amino acids, aspartic acid, and glutamic acid, occur more frequently in nature than basic nitrogen-containing ones. Ca(I1) would then be more widely useful than the other cations in this respect. The other relevant character is the size of Ca(I1): 110-120 pm; this is much greater than those of the common cations, Mg(I1) and Zn(I1). Because of this, the Ca(1I)'s coordination is rather flexible, allowing Ca(I1) fit into different structures having a wide range of formation constants. The formation constants of Ca(I1)-orotein ranee tvuicallv from lo3 M-' to 109 M-I. This ~ o r r & ~ o n dtos the physioiogical concentration range of Ca(I1) of M to 10-8M. One of the effects of coordination of a cation to a protein 1s the alteration of its conformation. Ca(II), because of its rather lower ionic potential (ionic chargelionic radius), would not be as effective as Me(I1) or Zn(II), . . hut certainly better than Na(1) or K(I) in thLs'respect. Another relevant parameter is a kinetic one; i.e., bow fast a cation can bind to a protein. As a measure of such a parameter, the rates of water exchange of metal aquo complexes may be utilized. Such arate (in unitsof s-I a t 25 OC) has been determined to be lo8 for Ca(II), 2 X lo7 for Zn(I1) and Mn(II), 7 X 105 for Mg(I1). That is, Ca(I1) would be able to hind to and dissociate from a protein more rapidly, perhaps 100-fold or so than M d I I ) does. All told, Ca(II), among the most common divalent cations, seems to best meet requirements (1)and (2) above. I t may be needless to point out that Zn and'hin are&ch less abundant than Ca o; Mg. Because of their widespread needs, the cytosolic concentrations of MgfII),KfI), and CI- are relatively high, heing of
M. Therefore, it would be rather difficult to the order of rapidly change their concentrations by as much as 100-fold, because a much larger quantity needs to be transported, as compared to the case of Ca(I1). These considerations, based on some ideas expressed by Blaustein (16) and Levine and Williams (In,seem to lead to a conclusion that Ca(I1) is best fit for the job. Concluding Remark
I t has been shown that the physiological requirements for the SM function seem to be best met by Ca(I1) among the common cations. The basis for this contention can be understood in terms of the very basic chemistry of Ca(II), as in the cases of more common functions of biological elements as explored in the previous articles of this series (18-20). Lnerature Clted
Voi. Ill. pp 1-36. 8. Berridge, M. J. In Colrivm in Biological Syafams:Rubin, R. P.,et al, Eds.; Plenum: 1985; p 37: Berridge. M. J. Ann. Rsu. Biorhom. 1981.56.159-193:Beyridge. M. J.; Irvine,R. F.Nnfure 1989,341,197-205. 9. ~ ~ k aY.: i ~ishimofo. , A,:~ i s h i z u k aY., In colrium and CdIFunction:Cheung, W. Y.. Ed.; Academic: 1982:Vol. 11, pp 385-412. 10. Alelandere. J.;Lss~alles,J. P.: Kado, R. T. Nature 1930,343,567-570. 11. ~lberta.B.; Bray. D.;Lewis, I.;R a f t M.: Robert8.K.;Watson. J. D. MotculorBialogy oftho CdkGarland: 1983:Chaptex13. 12. Potter, J. D.: Johnson. J. D. In Cokium and Cell Funlion; Choung, W. Y., Ed.: Aeademb: 1982; Vol. 11,pp 145.173. 13. Herrber8.G.: Jone8,M.N. G. Nolure 1984,313.653-659. 14. Sundaralingam, M.; Bergstram, R.: Strasburg, G.;Rao, S. T.: Roychowdhury, P.; Greser, M.; Weng, B. C. Science 1985,227.945-948. 16. Bitar, K. N.;Brsdford,P.;Putney, J. W., JI.; Makh1ouf.G. M. Science 1986,232,11431145. 16. Blausfein. M. P. In Cotium in Bioiogicol Swtem;Rubin, R. P., et a]..FA Plenum: 1985: pp 23-33. 17. Levine.B. A,:Williams, R. J. P. In Coleium and Cell Function; Cheung, W. Y.,Ed.; Academic: 1982: Vol. 11, pp 138. 18. Ochiai, GI. J. Chem. Edue. 1978,55,631. 19. Oehiai, GI. J. Cham. Edue. 1984.63.942. 20. Oehisi. 6 1 . J. Chrm.Educ. 1988.65.943.
1991 James Flack Norris Award: Nominations Nominations are heing received for the 1991James Flack Norris Award for Outstanding Achievement in the Teaching of Chemistry. The Norris Award, one of the oldest national awards of the American Chemical Society, is presented annually by the Northeastern Section and consists of a certificate and an honorarium of $3,000. Nominees can be from anywhere in the world and must have served with special distinction as teachers of chemistry at any level: secondary school, college level, or graduate school. This must he attested by broad evidence of their wide-ranging effect on the teaching of chemistry end of their effectiveness beyond the local classroom. Recent winners have included eminent teachers at all levels such as Louis Fieser, Joel Hildebrand, Bassam Shakhashiri, Dana Mayo-Ronald Pike, Jerry Mohrig, and a slate of effective teachers .---. ~ ~ at all levels. The awardee for 1990 was Joseph A. Schwarcz who was honored at the traditional formal dinner ceremony in Boston on Novemher 8. Nominations for 1991will he received until April 15,1991. Nominatingmaterialsmust be limited to 30 pages and focus specifically on the nominee's contributions to and effectiveness in teaching chemistry. This should include a thorough curriculum vitae with listings of honors, awards, and publications that relate to education. There must he a nominating letter and as many seconding letters as are necessary to convey the nominee's qualificationfor this award for outstanding achievement in teaching chemistry. For example,these letten could show the impact of the nominee's teaching in inspiring students to spend their professional life in chemistry, or could show how the nominee succeeded in reaching a broader, national or international, audience through textbooks, articles, or other more innovative efforts. Material should be of standard 81/2X 11size for binding but should not include reprints or books. Nominating materials should be sent before April 15 to Robert O'Malley, Department of Chemistry, Boston College, Chestnut Hill, MA 02167. ~
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