Protein hydrophobicity and stability support the thermodynamic theory of protein degradation

Rat liver enzymes were used to study the relationship between their in vivo half-lives and their apparent hydrophobicity or their resistance to inactivation by mechanical shaking. The apparent hydrophobicity of these enzymes, measured as the percent of the protein recovered from an octyl-Sepharose column, is correlated with their known half-lives (r = 0.75, P less than 0.01). The presence of specific ligands which are known to increase compactness by impeding unfolding of proteins decreased the apparent hydrophobicity of fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase. Resistance of enzymes to inactivation by mechanical shaking correlated well with their in vivo half-lives (r = 0.90, P less than 0.01). When the shaking experiments were done in the presence of substrates, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase were protected from inactivation.