Formation of collagen hydroxyproline in vitro.

Stetten & Schoenheimer (1943) fed [15N]proline to young rats and showed it to be a good source of the hydroxyproline of the carcass protein. Later, Stetten (1949) found that the efficiency of dietary [15N]hydroxyproline was less than one-twentieth of that of proline as a precursor of collagen hydroxyproline. These findings are of considerable interest since they are contrary to the general observation that proteins are built up from their constituent free amino acids (Loftfield, 1957). The only close parallel, discovered subsequently, is the formation of collagen hydroxylysine from lysine (Sinex & Van Slyke, 1955; Piez & Likins, 1957), but not from free hydroxylysine (Sinex & Van Slyke, 1957). Stetten (1949) suggested that free hydroxyproline was not an intermediate in collagen biosynthesis and that hydroxylation of the proline residues occurred at the protein or peptide stage. The hydroxylation of