Calcium in biological systems

Abstract

In physiological fluids calcium ion takes part in many processes. Among these are muscle contraction, microtubule formation, hormonal responses, exocytosis, fertilization, neurotransmitter release, blood clotting, protein stabilization, intercellular communication, mineralization, and cell fusion, adhesion, and growth. Most of these Ca 2+ related activities occur by interactions with proteins, which Ca 2+ may stabilize, activate, and modulate. In extracellular fluids the free or weakly bound Ca 2+ concentration is about 1 m M. Within many cells the free Ca 2+ concentration in the cytosol is only 0.1 μ M, 10 −4 times less than in extracellular fluids. Cell membranes contain pumps, Ca-ATPases, that aid in maintaining the extraordinary concentration gradient. However, a substantial amount of Ca 2+ occurs within cells, some of it bound tightly to proteins. In response to a stimulus the free Ca 2+ concentration may increase about 10 times. Thus proteins that participate in these responses possess Ca 2+ dissociation constants in the μ M range. The cytosolic Ca 2+ concentration change is achieved rapidly, and free Ca 2+ serves as a messenger or trigger for other interactions. Ca 2+ sites in proteins are composed of negatively charged and neutral oxygen donors; nitrogen donors seem unlikely, and none have been found. Protein oxygen donors derive from carboxylate groups, carbonyl oxygens of the amide backbone, and hydroxy groups of serine and threonine side chains. Ca 2+ varies in its coordination number and bond lengths. The frequency of Ca 2+ coordination numbers decreases in the order 8 > 7 > 6 > 9. Coordination about Ca 2+ is basically ionic and spherical. Ca 2+O bond distances range from 2.3 to 2.6 Å. In solution, even within a single complex, there may be variability in bond distances and, in many cases, coordination number. To bind Ca 2+, proteins provide a pocket of appropriate size and shape with two or more negatively charged carboxylate side chains. Specific applications of these general principles appear in other papers in this symposium and in Vol. 17 of ‘ Metal Ions in Biological Systems’, H. Sigel, ed. Except for the charge difference, usually not crucial, tripositive lanthanide ions mimic many Ca 2+ properties. Energy transfer from a nearby excited aromatic chromophore produces Tb 3+ luminescence. The spectrum and relative intensity compared to the total luminescence intensity of the circularly polarized luminescence from parvalbumin and troponin-C are nearly identical. Specific Ca 2+ binding sites in the two kinds of proteins are therefore similar. The excitation spectrum identifies the donor group in the energy transfer process as a phenylalanine side chain in parvalbumin and a tyrosine side chain in troponin-C. The two amine acids comprise homologous pairs in the two proteins.