Superoxide dismutases, SOD, are enzymes which catalyze the dismutation of superoxide, O-2, and contain iron, manganese or copper-zinc in the active sites. The iron-and manganese-containing SODs occur mainly in prokaryotes and the copper, zinc-SOD in eukaryotes. The primary structure of the enzymes have been determined in the Mn-SODs from E. coli and B. stearothermophilus and in the Cu, Zn-SODs from human and bovine erythrocytes and from baker's yeast. The molecular structural data are available only for the bovine enzyme. The enzyme consists of two identical subunits, each of which contains one Cu (II) and one Zn (II) bridged by an imidazolate anion from the side chain of histidine. The Cu (II) ion is coordinated to four histidine imidazoles and the Zn (II) to three imidazoles and one carboxylate of aspartic acid. The Cu (II) -bridged imidazole bond is dissociated upon reduction of the enzyme. The structure and function of the Cu, Zn-SOD are reviewed from the chemical view-points.
Recent advances in the biomimetic chemistry of metal complexes of porphyrins and related compounds are briefly reviewed. Selected topics include (i) higher valent oxometalloporphyrins with relevance to the proposed intermediates in the enzymatic reactions of cytochrome P450, peroxidase, and catalase, (ii) myoglobin and hemoglobin models to elucidate the possible protein control of heme reactivities, and (iii) some novel redox behaviors of metalloporphyrins and related compounds. Some clinical chemistry of chlorophyll derivatives are also described.
Recent advances in studies on the mechanism of action of vitamin B12 coenzymes and on the biosynthesis of vitamin B12 are reviewed. Adenosyl-B12 is the first known naturally occurring organometallic compound containing a stable Co-C sigma bond. This coenzyme participates in the eleven seemingly different enzymatic rearrangement and reduction reactions, and has been well established to act as an intermediate hydrogen carrier. It is generally accepted that the early event in the reactions is the cleavage of the Co-C bond of the enzyme-bound coenzyme, which leads to generation of the catalytic center. A possible role of the apoprotein in activation of the Co-C bond of the coenzyme, which is essential for manifestation of functions of the coenzyme, is discussed on the bases of the structure-function relationship of B12 coenzymes in the diol dehydrase reaction and of the apoenzyme-coenzyme interactions. The biosynthetic route for vitamin B12 is also briefly summarized here with emphasis on the ring contraction step in formation of the corrin nucleus.
The history of the study of zinc enzymes and their characteristics and the classification are briefly surveyed, together with the general remarks on the structure and function of metals in metalloenzymes. Among about 90 zinc enzymes so far discovered, special emphasis is placed on horse liver alcohol dehydrogenase and the recent experimental results of UV-VIS spectra, circular dichroism and X-ray crystallography are presented. The M. W. of horse liver alcohol dehydrogenase is 80, 000 and the enzyme consists of two subunits, each of which contains two zinc atoms, and 2 mols of NAD+ is necessary as cofactor for the enzyme. The details of the structure and the function of zinc in the enzyme are discussed and the possible reaction mechanism is explained. The paper also briefly introduces the recently extracted human liver alcohol dehydrogenase.
Recent developments of research in the field of molybdenum enzymes are briefly reviewed. Structures of active sites of nitrogenase and xanthine oxidase are proposed on recent reports. Some important inorganic model complexes having characteristic coordination of sulfur atoms to Mo were listed and their relevance to the corresponding enzymes are discussed.
Metallothionein is named for its characteristic structure, a low molecular weight metal-binding protein (61 amino acid residues) rich in cysteinyl residues (20 residues) and heavy metals (7 metals for zinc and cadmium). Heavy metals which can induce and can be bound to metallothionein are restricted to seven heavy metals (zinc, copper, cadmium, silver, mercury, gold, and bismuth). Namely, heavy metals with higher affinity than zinc can be bound in vivo to metallothionein.Other heavy metals such as nickel, manganese, chromium, and so on can also induce metallothionein but can not be bound to metallothionein and the induced metallothionein contains only zinc or zinc and a small amount of copper. A great diversity of stresses other than heavy metals such as starvation, operation, administrations of alkylating agents and inflammatory drugs also induces metallothionein. Glucocorticohormone which may be related to the stresses also induces metallothionein and high concentrations of metallothionein are observed in the livers of foetus and neonatus. Biological functions of metallothionein have been postulated to be a protective protein from harmful heavy metals and a regulating protein for the homeostasis of zinc and copper.
Cleavage of cellular DNA by bleomycin substantially contributes to the antitumor activity of this drug. Two characteristics are necessary for antineoplastic action of bleomycin. First, the bithiazole region of the antibiotic has an affinity for the guanine base of DNA. Second, the β-aminoalanine-pyrimidine-β-hydroxyhistidine portion of the drug is capable of oxygen activation by the complexation with Fe (II) ion. The role of the gulose-mannose group and unique interaction between the iron-coordination site and the DNA-binding site have been also indicated. Several spectroscopic data have clearly demonstrated that the bleomycin-Fe (II) complex forms a complex with either CO, C2H5NC, or NO. The “site specific oxygen radical”, produced from an active bleomycin-Fe (II) complex, would account for the action mechanism of selective DNA base cleavage by bleomycin. In addition, the inactivation mechanism of bleomycin hydrolase and important effect of the fifth axial amino group to iron-coordination on bleomycin activity have been discussed.
Many of the elements in the soil circulate through the ecosystem : soil (source) →plant (assimilator) →animal (predator) →microorganism (decomposer) →soil. In this circulation of elements, plant occupies a special and important position that the elements in the lithosphere firstly enter into the biosphere. Since 1900, the information on the existence and roles of trace metals in the plant has been much accumulated. These knowledges enable us not only to increase the crop yield but also to cure the disorders of crop, cattle and human caused by deficiency and excess of trace metals in the soil. In this paper such topics of essential (Cu, Zn, Mo, Mn, Fe) and non-essential (Cd, Al, Ge, Cr, Co, Ni, ) trace metals are briefly presented.