Publisher Summary This chapter discusses the role of free radicals and catalytic metal ions in human disease. The importance of transition metal ions in mediating oxidant damage naturally leads to the question as to what forms of such ions might be available to catalyze radical reactions in vivo . The chapter discusses the metabolism of transition metals, such as iron and copper. It also discusses the chelation therapy that is an approach to site-specific antioxidant protection. The detection and measurement of lipid peroxidation is the evidence most frequently cited to support the involvement of free radical reactions in toxicology and in human disease. A wide range of techniques is available to measure the rate of this process, but none is applicable to all circumstances. The two most popular are the measurement of diene conjugation and the thiobarbituric acid (TBA) test, but they are both subject to pitfalls, especially when applied to human samples. The chapter also discusses the essential principles of the peroxidation process. When discussing lipid peroxidation, it is essential to use clear terminology for the sequence of events involved; an imprecise use of terms such as initiation has caused considerable confusion in the literature. In a completely peroxide-free lipid system, first chain initiation of a peroxidation sequence in a membrane or polyunsaturated fatty acid refers to the attack of any species that has sufficient reactivity to abstract a hydrogen atom from a methylene group.

Role of free radicals and catalytic metal ions in human disease: an overview.

Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts.

A progressive alignment method is described that utilizes the Needleman and Wunsch pairwise alignment algorithm iteratively to achieve the multiple alignment of a set of protein sequences and to construct an evolutionary tree depicting their relationship. The sequences are assumed a priori to share a common ancestor, and the trees are constructed from difference matrices derived directly from the multiple alignment. The thrust of the method involves putting more trust in the comparison of recently diverged sequences than in those evolved in the distant past. In particular, this rule is followed: “once a gap, always a gap”. The method has been applied to three sets of protein sequences: 7 superoxide dismutases, 11 globins, and 9 tyrosine kinase-like sequences. Multiple alignments and phylogenetic trees for these sets of sequences were determined and compared with trees derived by conventional pairwise treatments. In several instances, the progressive method led to trees that appeared to be more in line with biological expectations than were trees obtained by more commonly used methods.

Progressive sequence alignment as a prerequisite to correct phylogenetic trees.

Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression

Disturbance of the balance between the production of reactive oxygen species such as superoxide; hydrogen peroxide; hypochlorous acid; hydroxyl, alkoxyl, and peroxyl radicals; and antioxidant defenses against them produces oxidative stress, which amplifies tissue damage by releasing prooxidative forms of reactive iron that are able to drive Fenton chemistry and lipid peroxidation and by eroding away protective sacrificial antioxidants. The body has a hierarchy of defense strategies to deal with oxidative stress within different cellular compartments, and superimposed on these are gene-regulated defenses involving the heat-shock and oxidant stress proteins.

Lipid peroxidation and antioxidants as biomarkers of tissue damage.

The production of free radicals during the autoxidation of cysteine and their effect on isolated rat hepatocytes

The primary structure of human liver manganese superoxide dismutase.

Enhanced production of hydroxyl radicals by the xanthine-xanthine oxidase reaction in the presence of lactoferrin

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2880%2981044-1

J.V. Bannister

Papers

The production of free radicals during the autoxidation of cysteine and their effect on isolated rat hepatocytes

The primary structure of human liver manganese superoxide dismutase.

Enhanced production of hydroxyl radicals by the xanthine-xanthine oxidase reaction in the presence of lactoferrin

THE COMPLETE AMINO ACID SEQUENCE OF HUMAN Cu/Zn SUPEROXIDE DISMUTASE

A mechanism for primaquine mediated oxidation of NADPH in red blood cells.