The analysis of glutamate and glutamine frequencies in human proteins as marker of tissue oxygenation

In this study, we investigated whether the relative abundance of glutamate and glutamine in human proteins reflects the availability of these amino acids (AAs) dictated by the cellular context. In particular, because hypoxia increases the conversion of glutamate to glutamine, we hypothesized that the ratio glutamate/glutamine could be related to tissue oxygenation. By histological, biochemical and genetic evaluation, we identified proteins expressed selectively by distinct cellular populations that are exposed in the same tissue to high or low oxygenation, or proteins codified by different chromosomal loci. Our biochemical assessment was implemented by software tools that calculated the absolute and the relative frequencies of all AAs contained in the proteins. Moreover, an agglomerative hierarchical cluster analysis was performed. In the skin model that has a strictly local metabolism, we demonstrated that the ratio glutamate/glutamine of the selected proteins was directly proportional to oxygenation. Ac...