The Jan. 21 issue of the Journal of Biological Chemistry contained two classic articles by Edmond H. Fischer, who shared the 1992 Nobel Prize in physiology or medicine with Edwin G. Krebs for their research on reversible protein phosphorylation.
Krebs trained with Carl and Gerty Cori, who discovered that muscle phosphorylase exists in two forms: phosphorylase a, which is easily crystallized and active without the addition of AMP, and phosphorylase b, a more soluble protein, which is inactive without AMP.
Previously, however, Fischer had purified potato phosphorylase, which had no AMP requirement. It seemed unlikely to Fischer and Krebs that muscle phosphorylase but not potato phosphorylase would require AMP as a cofactor, so they set out to elucidate the role of AMP in the reaction. They never discovered what the nucleotide was doing, but they did discover that muscle phosphorylase was regulated by an enzyme-catalyzed phosphorylation-dephosphorylation reaction.
The articles reprinted this January were both first published in JBC in 1955.
In the first, Krebs and Fischer describe experiments meant to determine whether environmental temperature affects the phosphorylase content of skeletal muscle. Though unable to detect temperature effects, they did make the surprising discovery that the muscle extracts contained mainly phosphorylase b rather than phosphorylase a.
In the second article, the researchers examine the requirements for the phosphorylase conversion and show that the conversion of phosphorylase b to phosphorylase a in cell-free muscle extracts requires a nucleotide containing high-energy phosphate and a divalent metal ion.
Angela Hopp (email@example.com) is managing editor for special projects of the Journal of Biological Chemistry.