Liver phenylalanine hydroxylase activity in relation to blood concentrations of tyrosine and phenylalanine in the rat

Abstract

The plasma concentration of phenylalanine and tyrosine decreases in normal rats during the first few postnatal days; subsequently, the concentration of phenylalanine remains more or less constant, whereas that of tyrosine exhibits a high peak on day 13. The basal concentrations of the two amino acids were not altered by injections of thyroxine or cortisol, except in 13-day-old rats, when an injection of cortisol decreased the concentration of tyrosine. In young rats (13-15 days old), treatment with cortisol increased the activity of phenylalanine hydroxylase in the liver (measured in vitro) and accelerated the metabolism of administered phenylalanine: the rate constant of the disappearance of phenylalanine from plasma and the initial increase in tyrosine in plasma correlated quantitatively with the activity of phenylalanine hydroxylase in the liver. In adult rats, the inhibition of this enzyme (attested by assay in vitro) by p-chlorophenylalanine resulted in a proportionate decrease in tyrosine formation from an injection of phenylalanine. However, the quantitative relationship between liver phenylalanine hydroxylase activity and phenylalanine metabolism within the group of young rats was different from that observed among adult rats.

Lipid Metabolism in Liver and Brain in Acute Hyperphenylalaninemia in Rats of Different Ages

“…During the developmental ages studied, phenylalanine levels held constant or increased somewhat while tyrosine levels generally decreased. The plasma levels were similar to those recently reported [26] in control rats, although the increases in plasma tyrosine in 10-to 14-day old rats, and especially in 13-day-old rats, were greater than those observed in the present study in 11-or 14-day-old control-injected rats. Cortisol injections caused a decrease in plasma tyrosine in 11-to 13-day-old rats [26].…”

“…The plasma levels were similar to those recently reported [26] in control rats, although the increases in plasma tyrosine in 10-to 14-day old rats, and especially in 13-day-old rats, were greater than those observed in the present study in 11-or 14-day-old control-injected rats. Cortisol injections caused a decrease in plasma tyrosine in 11-to 13-day-old rats [26]. The lesser magni tude and greater variability of the plasma tyrosine elevation seen in 11-dayold rats (table I) may have been the result of an adrenocortical response to the water injections the control group received.…”

The regulation of phenylalanine hydroxylase in rat tissues in vivo. The maintenance of high plasma phenylalanine concentrations in suckling rats: a model for phenylketonuria

“…The amount of hepatic phenylalanine hydroxylase (judged by its activity in an optimally fortified assay system in vitro) appears to be the primary determinant of the capacity to metabolize phenylalanine in vivo: in adult rats, this was demonstrated with the aid ofthe inhibitor p-chlorophenylalanine (Guroff, 1969); in suckling rats, as we previously reported (McGee et al, 1972b), cortisol-induced elevations of phenylalanine hydroxylase activity correlated quantitatively with increases in the rate constant of disappearance of a loading dose ofphenylalanine from plasma. However, major changes in rate constant altered by only about 30min the time-period during which the plasma phenylalanine concentration remained considerably above normal.…”

Experimental determination of the phosphorylation state of phenylalanine hydroxylase

“…However, the ability ofboth these effectors to diminish glucagon-stimulated increases in liver cell cyclic AMP concentrations may be a significant factor (Bosch et al, 1986). Analysis of the phosphorylation state of phenylalanine hydroxylase in isolated kidney tubules Although the major site of phenylalanine hydroxylase activity is the liver, there is evidence for an appreciable enzyme activity in the kidney cortex (McGee et al, 1972). There appears to be a basic similarity between the enzyme from these sources; however, there are indications that the regulation of the enzyme may show some tissue specificity (Rao & Kaufman, 1986).…”