Trace metals, association with enzymes

Artificial liver support systems aim at the extracorporeal removal of water soluble and protein-bound toxins (albumin being the preferential binding protein) associated with hepatic failure. Albumin contains reversible binding sites for substances such as fatty acids, hormones, enzymes, dyes, trace metals and drugs [26] and therefore helps elimination by kidneys of substances that are toxic in the unbound state. It should be noticed that the range of substances to be removed is broad and not completely identified. Clinical studies showed that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile adds, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be benefidal to the dinical course of a patient in liver failure. 

Ageing and the degenerative diseases associated with it are attributed basically to the deleterious side attacks of free radicals on cell constituents and on the connective tissues. The free radicals probably arise largely through reactions involving molecular oxygen catalysed in the cell by oxidative enzymes and in the connective tissues by traces of metals such as iron, cobalt, and manganese. 

Since traces of cations like copper can catalyze the oxidation of reduced GSH by molecular oxygen, it seemed possible that the effect of these metals might be an indirect one associated with a catalysis of the reoxidation of GSH by O2. That this is not the case was shown by comparing results obtained aerobically with those obtained anaerobically. Representative results are shown in Table III. It is clear that the amount of GSH formed is not increased under anaerobic conditions. The inhibiting cations appear to have an effect on the protein itself, and the nature of the more effective inhibitors suggests that free SH groups are necessary for enzyme activity. 

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