title: GAPDH in anesthesia.
abstract: Thus far, two independent laboratories have shown that inhaled anesthetics directly affect GAPDH structure and function. Additionally, it has been demonstrated that GAPDH normally regulates the function of GABA (type A) receptor. In light of these literature observations and some less direct findings, there is a discussion on the putative role of GAPDH in anesthesia. The binding site of inhaled anesthetics is described from literature reports on model proteins, such as human serum albumin and apoferritin. In addition to the expected hydrophobic residues that occupy the binding cavity, there are hydrophilic residues at or in very close proximity to the site of anesthetic binding. A putative binding site in the bacterial analog of the human GABA (type A) receptor is also described. Additionally, GAPDH may also play a role in anesthetic preconditioning, a phenomenon that confers protection of cells and tissues to future challenges by noxious stimuli. The central thesis regarding this paradigm is that inhaled anesthetics evoke an intra-molecular protein dehydration that is recognized by the cell, eliciting a very specific burst of chaperone gene expression. The chaperones that are implicated are associated with conferring protection against dehydration-induced protein aggregation.
authors.affiliation: Department of Biochemistry, Kansas City University of Medicine and Biosciences, Kansas City, MO, USA.
authors.forename: Norbert W
authors.initials: NW
authors.lastname: Seidler
mesh_terms: D000758:Anesthesia / Q000379:methods*; D001665:Binding Sites; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D018832:Molecular Chaperones; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases