Doris Doeden

Tryptophan Metabolism in Man

The amino acid tryptophan is unique because it contains the indole nucleus and because it is metabolized in man through several different biochemical pathways to a number of specific products. It is the precursor of serotonin and 5-hydroxyindoleacetic acid. In addition, after cleavage of the indole ring, it may be metabolized by way of the kynurenine pathway to 3-hydroxyanthranilic acid and ultimately to nicotinamide. In mammalian liver the benzene ring is oxidized and metabolized through a number of intermediate reactions to glutarate, acetate, and carbon dioxide (1, 2). Tryptophan is also the precursor of indolic acids, such as 3-indoleacetic acid. In man this compound is formed both by tissue enzymes and by bacteria in the gut (3). In the intestinal tract, bacteria that contain tryptophanase (4) reductively cleave the side chain of tryptophan and form indole, which is absorbed, conjugated in the liver, and excreted as indican (sulfated potassium ester of indoxyl). In addition to the various reactions involving the indole ring or side chain, tryptophan, like other amino acids, is incorporated into protein. These pathways are schematically shown in Figure 1. The many different enzyme systems and important cofactors, such as pyridoxal phosphate, that take part in these reactions have been ably reviewed (5-7) and will not be discussed here. In the investigation of tryptophan metabolism in man, a number of variables must be considered. These include not only these enzymes and cofactors, but

Homotransplantation of the liver in a patient with hepatoma and hereditary tyrosinemia

A girl with hereditary tyrosinemia, diagnosed at 6 months of age, was treated with a diet restricted in phenylalanine and tyrosine. At 9 1/2 years of age she developed an acutely enlarged liver and spleen, and the diagnosis of hepatocarcinoma was made. The patient received a liver transplant and tyrosine metabolites became normal while she was receiving a regular diet. Three months later, an infected thrombosis of the portal vein caused her death. Liver transplant appears to be an effective method of enzyme replacement in tyrosinemia and should be considered for prevention of hepatoma.

Labeled Methionine as an Indicator of Protein formation in Children with Lipoid Nephrosis.

Summary 1. The rate of serum protein formation as indicated by the incorporation of methionine labeled with S35 was determined in 4 patients with lipoid nephrosis and in two control subjects. 2. The rate of serum protein formation thus determined would appear to be greater in the nephritic patients than in the control subjects.

Atypical phenylketonuric heterozygote. Deficiency in phenylalanine hydroxylase and transaminase activity.

A child with an elevated serum level of phenylalanine, a typical phenylketonuria phenylalanine tolerance test, an absence of increased urinary concentrations of phenylketones, ortho- and parahydroxyphenyl acids, and phenolic acids, as well as no abnormality in urinary excretion of 5-hydroxyindoleacetic acid or in indole-3-acetic acid is reported. It appears that this child has marked limitation in phenylalanine transaminase activity and, as a consequence, the characteristic associated biochemical abnormalities related to limited activity of this enzyme were not expressed and could not be evoked.

Fecal pseudomonas aeruginosa as a cause of the blue diaper syndrome

Summary A 9-day-old infant presented with blue-green discoloration of the stools due to a pigment elaborated by Pseudomonas aeruginosa . The child had no evidence of systemic disease; however, as the stool is the major source of potential gram-negative pathogens, a course of oral antibiotic therapy was given to eradicate the organism and the stools returned to normal color.