High impact information on HM-GSH

• The results strongly indicate that Arg-115 in class III alcohol dehydrogenase is a component of the binding site for activating fatty acids and is critical for the binding of S-hydroxymethylglutathione in glutathione-dependent formaldehyde dehydrogenase activity [1].
• The gene gfa is located directly upstream of the gene for glutathione-dependent formaldehyde dehydrogenase, which catalyzes the subsequent oxidation of S-hydroxymethylglutathione [2].
• The isotope-sensitive hydride transfer step is not significantly rate-limiting during catalysis by any of the forms, as evidenced by the near-unity primary deuterium isotope effects on both V and V/KS (for S-hydroxymethylglutathione); catalysis may be limited by the rate of dissociation of at least one (and possibly both) of the product molecules [3].
• This plant enzyme exhibits kinetic and molecular properties in common with the class III forms from mammals, with a K(m) for S-hydroxymethylglutathione of 1.4 microM, an anodic electrophoretic mobility (pI: 5.3-5.6) and a cross-reaction with anti-(rat class III alcohol dehydrogenase) antibodies [4].
• ADH3 (identical to glutathione-dependent formaldehyde dehydrogenase) is clearly the ancestral ADH form and S-hydroxymethylglutathione is the main physiological substrate, but the enzyme can still oxidize ethanol at high concentrations [5].

Anatomical context of HM-GSH

• Formaldehyde decreased the concentration of GSH in hepatocytes, probably by the extrusion of the CH2O-GSH adduct, S-hydroxymethylglutathione [6].

References