Feedback Control of Rat Liver Tryptophan Pyrrolase

• Published in: The Journal of biological chemistry Vol. 242; no. 6; pp. 1192 - 1198
• Main Authors: Cho-Chung, Yoon Sang, Pitot, Henry C.
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 25.03.1967
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)96163-6

The enzyme tryptophan pyrrolase, which catalyzes the first irreversible step in the degradative metabolism of tryptophan in mammalian liver, has been purified by a new procedure which is simple and affords relatively high yields. The highly purified enzyme has been found to be strongly inhibited by reduced nicotinamide adenine dinucleotide phosphate, which may be considered as the ultimate distal product of the conversion of tryptophan to functional nicotinyl derivatives. Kinetic analysis of the inhibition of tryptophan pyrrolase by NADPH indicates a type of "allosteric" inhibition. Other nicotinyl derivatives such as NADH, nicotinamide mononucleotide, nicotinamide, or nicotinic acid, are inhibitory to the enzyme, but only at considerably higher concentrations. Mild heating of purified tryptophan pyrrolase in the presence of tryptophan results in an enzyme which is no longer inhibited by NADPH but which still possesses a significant degree of tryptophan pyrrolase activity. Two fractions of tryptophan pyrrolase have been separated from each other on Sephadex G-200 columns. The highly active form of the enzyme, which is eluted with the void volume, is sensitive to NADPH inhibition, whereas the relatively inactive form, eluting well after the void volume, appears to be virtually insensitive to this inhibitor. On the basis of these studies the effect of NADPH upon tryptophan pyrrolase is postulated as conversion of a polymeric form of the enzyme to the monomeric, or relatively inactive, form by its action at a specific inhibitory site on the enzyme.