1. The plasma concentrations and urinary output of proline and hydroxyproline contained in peptides were measured in normal rats and in rats with Fanconi syndrome produced by injection of sodium maleate. All animals received a prior injection of 10 mg of the dipeptide l-prolyl-l-hydroxyproline to increase plasma and urinary peptide content. There was a significant increase of urinary output of the two imino acids contained in peptides and a fall in their plasma concentrations. 2. It is concluded that increased output of peptides derived from collagen degradation in the experimental Fanconi syndrome in rats is at least in part due to diminished tubular reabsorption of these compounds from the glomerular filtrate. The results are claimed to be relevant to the increased output of urinary peptides in the Fanconi syndrome in man.

1. A study has been made of urinary peptide output in rats before and after production of a Fanconi syndrome induced by a single injection of sodium maleate. There was an unequivocal increase of urinary peptides on the first and second days after the injection, without any detectable change in the concentration of plasma peptides. 2. Similar results were obtained in osteolathyritic rats in which skeletal lesions had been produced by ingestion of β-aminopropionitrile. 3. The fractional amino acid content of urinary peptides after maleate and β-aminopropionitrile is shown to be significantly different from that in control animals. 4. Evidence is presented that the increased output of peptides is mainly due to increased renal clearance similar to that previously described for amino acids, glucose and several electrolytes in this type of experimental Fanconi syndrome.

1. A study has been made of peptide excretion in twenty cases of Wilson's disease, ligand-exchange column chromatography being used to separate peptides from free amino acids. Previous reports of excess of peptide output in the disease were confirmed and the excess was shown to be highly significant statistically. 2. A considerable fraction of the excess of peptide output was shown to consist of hydroxyproline-containing peptides derived from collagen degradation. 3. The method of rank correlation showed that the difference both in free amino acid and peptide-bound amino acid output in cases of Wilson's disease and in control subjects was mainly quantitative; the pattern of amino acid excretion was qualitatively similar in both groups. 4. Evidence is presented that the increased copper output in the urine in the disease is not secondary to peptiduria.

1. Studies have been made of jejunal absorption rates in vivo in the rat of the stereoisomers of alanylphenylalanine, leucyl-leucine and glycyltryptophan. Absorption rates of l-alanyl-l-phenylalanine were about 200 times those of d-alanyl-d-phenylalanine, l-leucyl-l-leucine about 24 times those of the dd-isomer, and glycyl-l-tryptophan 5 times those of glycyl-d-tryptophan. The mixed ld- and ld-isomers were absorbed at intermediate rates. 2. Absorption rates were positively correlated with the rate of hydrolysis of each dipeptide by homogenates of rat intestinal mucosa. The transport rate and rate of hydrolysis of glycyl-d-tryptophan, d-alanyl-d-phenylalanine and d-leucyl-d-leucine were significantly greater in the ileum than in the jejunum. 3. When given by stomach tube the most slowly absorbed dipeptides, d-alanyl-d- phenylalanine, d-leucyl-d-leucine and glycyl-d-tryptophan were the only ones to be excreted in significant amounts in the urine, showing that they were absorbed as the entire molecule and were resistant to hydrolysis by tissue peptidases. 4. There was a close inverse correlation between the rates of transport by rat jejunum of glycine, d-alanine, d-leucine, d-phenylalanine, d-tryptophan, d-alanyl-d- phenylalanine, d-leucyl-d-leucine and glycyl-d-tryptophan and the molecular weight of each compound, suggesting that diffusion mechanisms play an appreciable part in jejunal absorption of these compounds. No such correlation was found in the case of the ileum.

1. The excretion of structural analogues of ammonia in acidic and alkaline urine was investigated. The lipid-soluble compounds n -propylamine, n -butylamine and n -amylamine and the water-soluble compounds hydrazine and methylhydrazine resemble ammonia in being more rapidly excreted in acidic urine. By contrast, the excretion of the water-soluble amines methylamine and ethylamine is unaffected by changes in urinary pH. 2. Arguments are advanced, based on the results, that pH-dependent excretion of ammonia is due to diffusion of the water-soluble un-ionized fraction through the aqueous phase of the cell membrane, and the same applies to the hydrazines. However that of n -propylamine and the higher-molecular-weight alkylamines is due to diffusion through the lipid phase of the cell membrane. The data suggest that this latter form of diffusion is the more rapid one. 3. After injection of glutamyl-γ-methylamide and the corresponding ethylamide, both methylamine and ethylamine excretions are significantly higher in acidosis, rising further in chronic acidosis. This indicates that the glutaminase II pathway of ammonia genesis increases in activity in the acidotic rat in vivo.

1. The intestinal transport of oligopeptides containing either lysine or arginine has been compared with that of the corresponding free amino acids in six homozygous cystinuric patients and in six normal adult subjects by use of the oral tolerance test technique. 2. No difference was found in the absorption of lysine from l-lysylglycine and an equivalent mixture of free lysine and glycine. 3. In comparisons of serum increments of lysine and arginine after oral casein and an equivalent free amino acid mixture there was no difference in the case of lysine but rise of serum arginine was higher in three cystinuric patients after the whole protein than after the amino acids. 4. Studies of urinary piperidine and pyrrolidine output in a single cystinuric patient supported the results of the tolerance tests. 5. Absorption rates of the dipeptides l-lysylglycine and l-arginyl-l-aspartate from an isolated loop of rat gut are compared with those of an equivalent free amino acid mixture. No difference was found for the former peptide, but in the latter absorption rates of arginine were higher after the amino acid mixture.