Protein glycation in vivo: Functional and structural effects on yeast enolase
Résumé
Protein glycation is involved in structure and stability changes that impair protein functionality, being associated with several human diseases, like diabetes and amyloidotic neuropathies (Alzheimer, Parkinson and Andrade's syndrome). To understand the relationship of protein glycation with protein dysfunction, unfolding and β-fibber formation, numerous studies have been made in vitro. All these previous experiments were conducted in non-physiologic or pseudo physiological conditions that bear little to no resemblance to what may happen in a living cell. In vivo, glycation occurs in a crowded and organized environment, where proteins are exposed to a steady state of glycation agents, namely methylglyoxal, while in vitro, a bolus of a suitable glycation agent is added to diluted protein samples. Yeast was shown to be an ideal model to investigate glycation in vivo since it shows different glycation phenotypes and presents specific protein glycation targets. A comparison between in vivo glycated enolase and purified enolase glycated in vitro revealed marked differences. All effects regarding structure and stability changes were enhanced when the protein was glycated in vitro. The same applies to enzyme activity loss, dimer dissociation and unfolding. However, the major difference lies in the nature and location of specific advanced glycation end-products. In vivo, glycation appears to be a specific process, where the same residues are consistently modified in the same way, while in vitro several residues are modified with different advanced glycation end-products.
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