The influence of starvation and tryptophan administration on the metabolism of phenylalanine, tyrosine and tryptophan in isolated rat liver cells

Abstract

Liver cells from fed Sprague-Dawley rats metabolized phenylalanine, tyrosine and tryptophan at rates consistent with the known kinetic properties of the first enzymes of each pathway. Starvation of rats for 48 h did not increase the maximal activities of phenylalanine hydroxylase, tryptophan 2,3-dioxygenase and tyrosine aminotransferase in liver cell extracts, when results were expressed in terms of cellular DNA. Catabolic flux through the first two enzymes was unchanged; that through the aminotransferase was elevated relatively to enzyme activity. This is interpreted in terms of changes in the concentrations of 2-oxoglutarate and glutamate. Cells from tryptophan-treated animals exhibited significant increases in the catabolism of tyrosine and tryptophan, but not of phenylalanine. The activities of tyrosine aminotransferase and tryptophan 2,3-dioxygenase were also increased, although the changes in flux and enzyme activity did not correspond exactly. These results are discussed with reference to the control of aromatic amino acid catabolism in liver; the role of substrate concentration is emphasized.

Hepatic mRNAs up‐regulated by starvation: an expression profile determined by suppression subtractive hybridization

“…Numerous well-studied starvation regulated genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and those for the urea cycle enzymes and amino acid catabolism enzymes, were not identified from our subtracted cDNA library. These enzymes are regulated at different stages of starvation, with an increase in hepatic PEPCK activity at 15 h following the onset of starvation (53), while an increase in the activity of urea cycle enzymes and amino acid catabolism enzymes occurs after 72 h of starvation (54,55). Because we studied the liver after 48 h of starvation, we would not expect to detect genes up-regulated after this time.…”

PKU mutation (D143G) associated with an apparent high residual enzyme activity: Expression of a kinetic variant form of phenylalanine hydroxylase in three different systems

“…The value of L-Phe in rat hepatocytes has been reported to be partly facilitated by a carrier mediated mechanism (Salter et al, 1986). Comparison of the rates of transport with the rates of metabolism (Salter et al, 1984), indicates that the transport process has a regulatory role in this pathway. In human blood, the molar ratio of phenylalanine/tyrosine is approximately 1 and 34 (McKean and Peterson, 1970) as compared to 0.6-0.7 and 1.4-3.2 in the hepatocytes (Choo et al, 1977) of normal individuals and PKU patients, respectively.…”

Selective Inhibitors of Tryptophan 2,3‐dioxygenase and Combined Inhibitors of Tryptophan 2,3‐dioxygenase and 5‐HT Reuptake as Novel Serotonergic Antidepressants

“…L-[ring-2-I4C] tryptophan is cleaved by TDO to yield unlabelled kynurenine and [I4C] formate (29). Measurement of the production of [I4C] formate in rat plasma after the administration of L-[ring-2-I4C] tryptophan therefore represents the activity of TDO in vivo.…”