Nitrogen, essential for the formation of amino and nucleic acids, building blocks of proteins and DNA, becomes very toxic in the form of free ammonia. Our liver converts ammonia to urea, through a series of biochemical reactions known as the urea cycle. Inherited metabolic disorders of one of the enzymes
involved in this cycle (Urea Cycle Disorders, UCDs) lead to accumulation of ammonia. Ammonia detoxification also relies on incorporation of ammonia into glutamate to form glutamine, a less toxic way to transport ammonia in the blood. Importantly, higher concentrations of glutamine in blood can indicate a rise of ammonia later on.
Thus, frequent monitoring of glutamine levels can prevent life-threatening metabolic derangements. While in the clinic measurements can be performed within a day, it takes 2-3 weeks for patients at home to obtain their glutamine levels, time in which a patient’s condition can
deteriorate. Moreover, for safety reasons, patients currently take more medication than needed when based on actual glutamine levels. Currently, there is no technology available to measure glutamine blood levels at home.
We work on a proof-of-concept study to measure glutamine in blood using the biological nanopore Cytolysin A (ClyA) in combination with the substrate binding domain 2 (SBD2), lending its selectivity towards glutamine to the ClyA pore. For this, ClyA we reconstitute into planar lipid bilayers and subjected to electrophysiological methods to observe the (un)binding of glutamine to SBD2. This method could then be integrated into microfluidic chips, offering a pathway to develop a home diagnostic device.
