Isotopic Studies on Collagen Degradation and the Urine Excretion of Hydroxyproline *

Although marked changes in collagen can be observed in a number of clinical conditions, ini- tial studies of the metabolic turnover of collagen suggested that this protein was metabolically more stable than other body proteins and that perhaps it was metabolically inert. After injecting glycine-C14 into rats, Neuberger, Slack (2), and Perrone (3) found that much less radioactivity was incorporated into collagen than into liver pro- teins. In addition, they found that the small amount of glycine-Cl" that did enter collagen dis- appeared with a half-life of over six weeks in young rats and longer in old rats. Subsequently, a number of investigators (4, 5) demonstrated rapid turnover rates in the small amount of "solu- ble" collagen which can be extracted from most tissues and is a precursor of insoluble collagen. Significant degradation of collagen, however, was not evident in studies performed directly on nor- mal tissues. Recently, Lindstedt and Prockop (6) attempted to study the metabolic turnover of collagen by injecting proline-Cl" into rats and then following the specific activity of urine hydroxyproline-C14. Since nearly all the hydroxyproline in vertebrates is found in collagen, and since the only source of this amino acid appears to be the hydroxylation of "bound" proline in situ (7, 8), the decay of urine hydroxyproline-C14 was assumed to reflect the degradation in vivo of collagen or its immediate precursors. The results suggested that although most of body collagen is metabolically stable, there are forms that are both synthesized and degraded rapidly under normal conditions.