Metal ions in biological catalysis: from enzyme databases to general principles

We analysed the roles and distribution of metal ions in enzymatic catalysis using available public databases and our new resource Metal-MACiE (http://www.ebi.ac.uk/thornton-srv/databases/Metal_MACiE/home.html). In Metal-MACiE, a database of metal-based reaction mechanisms, 116 entries covering 21% of the metal-dependent enzymes and 70% of the types of enzyme-catalysed chemical transformations are annotated according to metal function. We used Metal-MACiE to assess the functions performed by metals in biological catalysis and the relative frequencies of different metals in different roles, which can be related to their individual chemical properties and availability in the environment. The overall picture emerging from the overview of Metal-MACiE is that redox-inert metal ions are used in enzymes to stabilize negative charges and to activate substrates by virtue of their Lewis acid properties, whereas redox-active metal ions can be used both as Lewis acids and as redox centres. Magnesium and zinc are by far the most common ions of the first type, while calcium is relatively less used. Magnesium, however, is most often bound to phosphate groups of substrates and interacts with the enzyme only transiently, whereas the other metals are stably bound to the enzyme. The most common metal of the second type is iron, which is prevalent in the catalysis of redox reactions, followed by manganese, cobalt, molybdenum, copper and nickel. The control of the reactivity of redox-active metal ions may involve their association with organic cofactors to form stable units. This occurs sometimes for iron and nickel, and quite often for cobalt and molybdenum

Global epidemiology and outcomes of acute kidney injury

Acute kidney injury (AKI) is a commonly encountered syndrome associated with various aetiologies and pathophysiological processes leading to decreased kidney function. In addition to retention of waste products, impaired electrolyte homeostasis and altered drug concentrations, AKI induces a generalized inflammatory response that affects distant organs. Full recovery of kidney function is uncommon, which leaves these patients at risk of long-term morbidity and death. Estimates of AKI prevalence range from <1% to 66%. These variations can be explained by not only population differences but also inconsistent use of standardized AKI classification criteria. The aetiology and incidence of AKI also differ between high-income and low-to-middle-income countries. High-income countries show a lower incidence of AKI than do low-to-middle-income countries, where contaminated water and endemic diseases such as malaria contribute to a high burden of AKI. Outcomes of AKI are similar to or more severe than those of patients in high-income countries. In all resource settings, suboptimal early recognition and care of patients with AKI impede their recovery and lead to high mortality, which highlights unmet needs for improved detection and diagnosis of AKI and for efforts to improve care for these patients