The 1st Croatian Symposium on Membrane Transporters (1. Hrvatski Simpozij O Transporterima): a Short Introduction to the Relevance of Research on Transporters

Organisms are not isolated systems at equilibrium. Cells within an organism must exchange compounds with their environment by passing them across their biological membranes. In eukaryotic cells, transport across membrane-bound organelles such as the nucleus, endoplasmic reticulum, and mitochondria also occurs. Compounds commonly exchanged across membranes include metabolites such as glucose and pyruvate; ions such as sodium, potassium, calcium, and chloride; as well as amino acids and nucleotides. In addition, these cells have to deal with the uptake and/or effl ux of numerous endo-and xenobiotics and their metabolites. Essential components in this process are proteins called membrane transporters. Briefl y, they effectively carry various molecules to where they are needed, thus enabling the organism to run the metabolism, maintain the intracellular homeostasis of ions and other nutrients, perform functions, resist xenobiotics and pathogens, and make them more tolerant to internal and external stress and adverse conditions. Furthermore, contrary to traditional thought that most lipophilic substances enter cells by passive diffusion, it has recently become evident that very few molecules enter or leave cells, or cross organellar membranes, without the aid of proteins. Even the transport of molecules such as water and urea, which exhibit a limited diffusion across pure phospholipid bilayers, is largely accelerated by transport proteins. The human genome comprises at least 530 genes for plasma membrane transporters (1.7 % of total genes) and 350 genes for intracellular membrane transporters (1.1 % of total genes), which in terms of percentages is not much, but they do code for many proteins that are vital for cell functions. There are two major classes of membrane transport proteins: carrier proteins and channel proteins (ion channels and aquaporins). Carrier proteins (also called carriers, permeases, or transporters) bind the specifi c solute to be transported and undergo a series of conformational changes in order to transfer the bound solute across the membrane. Among them is a large superfamily of Solute Carriers (SLC in humans/Slc in animals and prokaryots; secondary or tertiary active transporters that include ion-coupled transporters, exchangers, facilitative transporters, etc.), which in humans contain 52 SLC gene families. Another superfamily of carrier proteins are ABC (ATP Binding Cassette; ABC in humans/Abc in animals and prokaryots) transporters, widely distributed in prokaryots and eukaryots, which bind and use the energy of hydrolysed ATP to transfer molecules across membranes (primary-active transporters). Channel proteins, on the other hand, need not bind the solute. Instead, they form hydrophilic …