Metabolic pathways for urea production by the amphibian kidney

Abstract
Homogenized kidneys, pooled from bullfrogs (Rana catesbiana), produce urea in amounts of 1.4–6.4 µmole/g of wet tissue after 1 hr of incubation in substrate-free media. The maximal rate of endogenous urea production under present conditions, 16 µmoles/g kidney per hr, was found during the first 10 min of incubation. In standard tests with added substrates, activity of frog kidney arginase was greater than that of frog liver arginase. However, argininosuccinase, easily detected in frog liver, dog liver, and dog kidney cortex, could not be detected in frog kidney. Additional tests showed that frog kidney homogenates contain uricase, allantoicase, and allantoicase in concentrations similar to those of frog liver tissue. This means that urea forming in frog kidney tissue comes from at least two pathways: one terminating in hydrolysis of arginine, and one terminating in hydrolysis of allantoic acid. In the absence of argininosuccinase, arginine could be derived from degradation of protein or peptides. In view of the oxygen dependency of uric acid-loaded homogenates, allantoic acid is derived from hydrolysis of allantoin which, in turn, derives from the oxidation of uric acid.