aging ͉ Caenorhabditis elegans ͉ oxidative stress ͉ signaling ͉ chaperone

Circulatory transport of the essential nutrient zinc primarily occurs through its binding to serum albumin. Here, we present the first crystal structures of mammalian albumins in complex with zinc. These structures, together with accompanying zinc binding data, allow identification of key zinc transport sites on human and equine albumins.

In mammalian blood plasma, serum albumin acts as a transport protein for free fatty acids, other lipids and hydrophobic molecules including neurodegenerative peptides, and essential metal ions such as zinc to allow their systemic distribution. Importantly, binding of these chemically extremely diverse entities is not independent, but linked allosterically. One particularly intriguing allosteric link exists between free fatty acid and zinc binding. Albumin thus mediates crosstalk between energy status/metabolism and organismal zinc handling. In recognition of the fact that even small changes in extracellular zinc concentration and speciation modulate the function of many cell types, the albumin-mediated impact of free fatty acid concentration on zinc distribution may be significant for both normal physiological processes including energy metabolism, insulin activity, heparin neutralisation, blood coagulation, and zinc signalling, and a range of disease states, including metabolic syndrome, cardiovascular disease, myocardial ischemia, diabetes, and thrombosis.

Fatty acid levels in the blood are dynamic and chronic elevation of plasma fatty acid levels is associated with some metabolic disorders such as cardiovascular disease and diabetes. Since the binding of Zn(2+) to albumin is important for the control of circulatory/cellular Zn(2+) dynamics, this relationship is likely to have important physiological and pathological implications. This article is part of a Special Issue entitled Serum Albumin.

Zn2+ is an essential regulator of coagulation and is released from activated platelets. In plasma, free Zn2+ concentration is fine-tuned through buffering by human serum albumin (HSA). Importantly, the ability...