Protein Synthesis

leucine to proline at amino acid position 1544(Ashcroft, 2005). This mutation simply reduce the activation of the channel by stimulatory nucleotide MgADP, as the NBDs sensitivity to this nucleotide is greatly/entirely lost. The failure of the channel activation means the open state of the channel pore is greatly reduced/blocked. This occurs as the inhibitory nucleotide (ATP) would have higher affinity for the channel than the activating nucleotide (MgADP). Closure of the K+ channel leads to depolarised state of the membrane. The voltage-gated calcium channel is therefore always open as the cell is depolarised constantly. Other example of mutations that cause hyperinsulinism by impairing the channel activation in response to metabolic inhibition are 3992-9G>A and E1506K. E1506K eliminates metabolic activation by reducing Mg2+ binding to the walker motif of SUR1, and thereby impairing Mg-nucleotide interaction. Mutation of 3992-9G>A is common in Ashkenazi population and can result in deletion of the entire NBD2 domain. Deletion of NBF-2 in 3992-9g→a alleles therefore, not only avoid binding of …show more content…
For example, C terminus of SUR1 has anterograde signal composed in part of leucine and phenylalanine which is required for the assembled channel to exist endoplasmic reticulum. Deletion of amino acids including phenylalanine reduces surface expression of KATP channels on the plasma membrane (Ashcroft, 2005). Another mutation that cause abnormal trafficking and is also common in the Ashkenazi population is the deletion codon for F1388. The inactivation of RKR ER retention signal in F1388-SUR1 leads to minimal surface expression (Nestorowicz et al., 1996). This means Kir6.2 is expressed more on the surface and the inhibitory effect on the channel is higher, leading to closed state of the