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YFF-Yngre, fremragende forskere

Physiological and pathological impacts of glutamine transporters

Awarded: NOK 10.0 mill.

Glutamine, the most abundant amino acid in the blood, is involved in a variety of metabolic processes such as biosynthesis of other substrates (eg proteins, nucleotides and amino sugars). It is also required for rapid cell growth such as in neoplasi. We h ave identified a family of amino acid transporters with high affinity for glutamine. Our initial characterization reveals isoform specific stoichiometrical and expressional differences. Coupling of glutamine transport to Na+ in symport and H+ in antiport makes the transport by SN1 and SN2 electroneutral and allows bi-directional transport depending on the concentration gradients of the substrates. In contrast, the unidirectional Na+-coupled SAT1-3 transporters generate high intracellular concentrations. B y working in concert, these transporters can shuttle glutamine between cells and organs. Studies implicate pivotal roles of these transporters in the generation of neurotransmitters (glutamate and GABA) in the brain, urea formation in the liver, insulin s ecretion in the pancreas and pH regulation in the kidney. To further understand the functional roles of these transporters and their involvement in pathology we aim at applying genetical and molecular biological approaches in different model systems to id entify mechanisms involved in their functional regulation. Thus, the project is expected to generate results of the highest quality and to reveal potential therapeutic targets. Successful outcomes will qualify us as the internationally leading investigato rs in the field.

Funding scheme:

YFF-Yngre, fremragende forskere