Crosstalk between zinc and free fatty acids in plasma

Abstract

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.

Graphical abstract

Highlights

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  Serum albumin binds and transports both free fatty acids and Zn ²⁺ ions

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  Elevated plasma free fatty acids impair Zn ²⁺ binding by albumin through an allosteric mechanism

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  The resulting changes in plasma zinc speciation are thought to impact blood coagulation and may promote thrombosis

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  Increased free Zn ²⁺ may lead to enhanced zinc export from plasma and dysregulation of zinc homeostasis in multiple tissues