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The ability of S-Acetyl-L-glutathione to be directly absorbed by cells and converted to GSH without needing breakdown into amino acids presents a significant advantage, especially in conditions where GSH synthesis may be impaired, such as during viral infections or in genetic disorders affecting GSH metabolism
This initial recognition step allows the peptides N-terminus to engage deep within the receptor TMD core, triggering a conformational change proximal to the intracellular region that results in G protein coupling and activation of the downstream signalling cascade 3,4,5,6,7
Importantly, the ECD of GLP-1R undergoes a remarkable orientation change from the closed TMD-interacting conformation to the extended active conformation during peptide binding and activation
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