ROLE OF METAL IONS IN BIOLOGICAL SYSTEMS

Metals are essential to a wide variety of biological processes in both prokaryotic and Eukaryotic systems. They play a crucial role in most of the metabolic path ways for example The movement of electrons in the electron-transfer pathways of photosynthetic organisms and in the respiratory chain of mitochondria is carried out by iron and copper containing proteins called as Cytochromes and plastocyanins. The water splitting centre of green plants (i.e. photo system II), which produces oxygen, is based on the sophisticated biological use of manganese chemistry. Iron is an essential element for blood production, iron containing proteins such as haemoglobin and myoglobin are essential for transferring and storage of oxygen in human beings i.e. they play a crucial role in the respiration. Likewise several metal ions play different roles in biological systems. Now I will explain you the major roles of metal ions in biological systems. 1) Metal ion functions in metalloproteins: Many of the naturally occurring proteins contain metal ions as cofactors, these are called as metalloproteins. The functional capabilities of the metalloproteins are enhanced due to the presence of these metal centres. These metalloproteins play different roles they are i) Dioxygen transport: One of the unique functions of metalloproteins is respiration. There are at least three types of oxygen transport proteins, they are Hemoglobin Myoglobin family, based on Fe Hemocyanin, based on Cu Hemerythrin, based on Fe

In all these respiratory proteins, a delicate balance is achieved where the O2 is coordinated to the metal ion in metalloprotein without undergoing any irreversible electron transfer. That means, no redox reaction occurs leading to no O-O bond rupture and as a result, no oxidation of metal ion takes place. ii) Electron transfer: There is another class of metalloproteins which are involved in the net electron transfer. These proteins undergo redox transformations and do not catalyze any reactions. These electron carrying molecules transfer their electrons to or from the enzymes. Cytochromes and iron-sulphur clusters are two of the most widely studied bio systems in bioinorganic chemistry.

2) Metal ion functions in metalloenzymes: Metalloproteins that perform catalytic functions are called as metalloenzymes or simply enzymes. They are also called as biocatalysts. This is a subclass of metalloproteins. The enzymes bring about the net transformation of the substrate by acting on it. The enzymes are generally named or grouped based on their functions in catalyzed reactions. For example, 1. Oxidoreductases These catalyze redox reactions 2. Transferases These bring about the transfer of functional groups from one substrate to another 3. Hydrolases These catalyze hydrolysis reactions 4. Lyases Catalyze Non-hydrolytic addition or removal of groups from substrates 5. Isomerases These facilitate the interconversion of isomers 6. Ligases These form new covalent bonds at the expense of ATP hydrolysis

It may be noted that within each functional type there are many types of metal centres that catalyze the required chemical reaction. Now I will explain you the functions of some of the metalloenzymes

Hydrolytic enzymes: These enzymes catalyze the addition or removal of water in a substrate molecule. Some of the best examples in this regard are Carbonic anhydrase promotes the hydrolysis of CO2 Peptidases or Esterases hydrolyze carbonyl compounds Phosphatases promote the cleavage of phosphate ester

In many of these hydrolytic enzymes, the active site is occupied by Zn +2 ion. The choice of Zn+2 at the active site has certain advantages like it lowers the pKa of the coordinated water, does not exhibit variable oxidation states and does not involve in any electron transfer. There are also other metal ions such as Mn+2, Ni+2, Ca+2 and Mg+2 which are encountered in hydrolytic enzymes and like zinc these ions show no tendency towards redox active chemistry.

Redox enzymes These are not like electron carrying proteins, but catalytically conduct oxidation or reduction reactions on the substrate molecules. These reactions generally involve two electron processes. Most common reactions of this type are addition of oxygen to the substrate or removal of oxygen from the substrate.

3) Role of metal ions in communication Metal ions are often used in biology as magnetic compasses, triggers for certain cellular processes and in regulating gene expressions. These are some of the cellular communication functions of metal ions. Some of the communication roles are Magneto tactic bacteria use magnetite (Fe3O4) as an internal compass Alkali and alkaline earth metal ions such as Na+, K+ and Ca+2 are used to trigger cellular responses. The zinc fingers regulate transcription in many proteins.

4) Interaction of metal ions with nucleic acids Metal ions interact directly with RNA and DNA, some of these interactions being nonspecific and the others being specific. In chemical point of view Nucleic acids (DNA and RNA) are actually salts (or complexes) of metal ions. It is impossible to separate the behaviour of DNA and RNA from their interactions with metal ions. Metal ions are usually required to promote and stabilize functionally active or native conformations of nucleic acids, as well as to mediate nucleic acid-protein interactions. However, certain metal ions can also cause structural transformation of nucleic acids, and induce their chemical modification and cleavage. Metal-nucleic acid interactions are involved in nucleotide biochemistry; genetic information storage and transfer, and control of gene expression, as well as in mutagenesis and carcinogenesis.

5) Metal ions in transport and storage The bioinorganic chemistry of metal ion transport and storage is an active area for investigation. It is important and of interest to know how the metal ions get into the cells and stored finally. Transport of metal ions can be carried out by

Special carrier molecules called Ionophores Large membrane spanning molecules called Ion channels Ion pumps which transport ions by using energy

Transport and storage of iron ion is studied well. Iron enters into bacterial cells due to its chelation to low molecular weight siderophores which belongs to a class of Ionophores excreted by bacteria. In mammals, iron is chelated and transported by the serum protein called transferrin. It is stored by another protein called ferritin, which has the capacity to bind nearly 4500 Fe+3 ions. Copper ion is transported by another serum protein called ceruloplasmin. There is also another protein called albumin which binds and transports copper ions.