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A method for quantitation of cycloleucine in biological fluids is described. Cycloleucine is oxidized to cyclopentanone by ninhydrin. The cyclopentanone formed is extracted into chloroform and determined by GLC. The method is accurate, convenient, rapid, and free of interference by other constituents of urine or serum.

Cycloleucine administration (a synthetic amino acid) to rats produces a selective hyperaminoaciduria concerning basic amino acids (arginine, ornithine, lysine) and cystine. The presence of the disulfide of cysteine and homocysteine was noted. The blood levels of these amino acids remain unchanged. The comparison between these biochemical anomalies and those observed in the human cystinuria-lysinuria allow to conclude the validity of this experimental pattern. However, its use is still limited because of the toxicity of Cycloleucine.

The formation constants of the mixed complexes which result by the reaction of metallic nitrilotriacetates with cycloleucine have been calculated for different temperatures. For the reaction of formation of mixed complexes Δ H f o and Δ S f o have also been calculated. The hydrolysis of metallic nitrilotriacetates has been studied at different temperatures and K h , Δ H h o , Δ S h o calculated.

SummaryCycloleucine administration to rats produces a generalized aminoaciduria which is largely the result of failure of renal tubular reabsorption. The greatest competition for renal tubular transport appears to be with the site for the dibasic amino acids.

Cycloleucine (1-aminocyclopentanecarboxylic acid) administration in cancer patients resulted in a reversible marked aminoaciduria consisting predominantly of cystine, ornithine, lysine, and arginine, with only minor elevations of other amino acids. Plasma levels of amino acids were essentially unchanged except for slight decreases in ornithine and lysine. This aminoaciduria is most likely due to a blockage by the drug of the renal tubular reabsorption of cystine, ornithine, lysine, and arginine, resulting in an aminoaciduria of the type seen in cystinuria.

An attempt has been made to evaluate some of the kinetic parameters governing the uptake of amino acids by muscle by measuring the steady-state concentration ratios established on incubation of the tissue in vitro. The data are analysed in terms of the steady state resulting from a balance between saturable uptake and efflux processes in conjuction with diffusion. For aminoisobutyrate and cycloleucine the data were compatible with efflux being solely by diffusion, but it was also possible to fit the data to conditions such that efflux by a saturable process and by diffusion were both occurring. Measurement of initial entry rates after preloading hearts with aminoisobutyrate gave results consistent with the first possibility only. Such measurements also suggested that the parameters governing a saturable uptake process changed during the course of uptake, but that the rate constant for diffusion remained the same. The rate of approach to equilibrium was found to be faster the higher the external concentration of amino acid. Both these observations would be consistent with accumulated amino acid progressively interfering with further operation of a carrier. For aminoisobutyrate the enhancement of accumulation in the presence of insulin appeared to result from an increase in the maximal velocity of the transport rate rather than from any change in apparent Km. For cycloleucine there was some diminution in the Km with insulin but again a rise in the transport rate.