The derivation of a quantitative model of phenylalanine metabolism in humans is described. The model is based on the kinetic properties of pure recombinant human phenylalanine hydroxylase and on estimates of the in vivo rates of phenylalanine transamination and protein degradation. Calculated values for the steady-state concentration of blood phenylalanine, rate of clearance of phenylalanine fr...

The biosynthesis of serotonin (5-hydroxytryptamine) involves, as a preliminary step, the hydroxylation of L-tryptophan to 5hydroxytryptophan, followed by decarboxylation of the 5-hydroxytryptophan formed (1). The second reaction has been demonstrated to occur in many tissues, and the enzyme responsible has been extensively studied (2). Two recent reports on the hydroxylation of tryptophan repre...

This chapter describes the aromatic L‐amino acids tryptophan and tyrosine and the effects on tyrosine metabolism of phenylalanine. Tryptophan and phenylalanine are essential amino acids and must ultimately be derived from dietary proteins; tyrosine is obtained both from dietary proteins and from the hydroxylation of phenylalanine by phenylalanine hydroxylase (PAH). The proportions of dietary tr...

Adult early treated hyperphenylalaninaemic patients can show specific deficits of prefrontal cortical functions. The development of additional therapeutic strategies for these patients requires the understanding of the mechanisms involved in phenylalanine-dependent impairment of fronto-cortical functions. We tested the hypothesis of phenylalanine interference with aminergic neurotransmission in...

Rhodamine-conjugated antibodies specific for phenylalanine hydroxylase and serum albumin were employed as cytochemical probes to identify these two proteins in H4 hepatoma cells and in isolated rat hepatocytes . Each fluorescent antibody stained the cells specifically and in a distinctive manner . In both cell types, albumin staining was discretely localized in cytoplasmic "bundles," whereas, p...

Phenylalanine hydroxylase that is essentially pure contains 1 to 2 moles of iron per mole of enzyme (assuming a molecular weight of 100,000). Electron spin resonance (ESR) studies have shown that the iron is present in the high spin ferric form. The addition of substrates (i.e. phenylalanine and dimethyltetrahydropterin) causes the signal for this form to disappear. The iron, 50 to 80%, can be ...

Maximum inhibition of phenylalanine hydroxylase activity in the liver (85%) and in the kidney (50%) of suckling rats required the administration of over 9 mumol of p-chlorophenylalanine/10g body weight. Despite the decrease in the total activity from 184 to 34 units per 10g body weight, the injection of as much as 26 mumol of phenylalanine was required for its concentration in plasma to be stil...

Higher serum neopterin is associated with increased mortality in patients with coronary artery disease (CAD). Preferentially Th1-type cytokine interferon- γ stimulates neopterin production by GTP cychlohydrolase I (GCH-I) in parallel in monocyte-derived macrophages and dendritic cells. In other cells, activation of GCH-I leads to the formation of 5,6,7,8-tetrahydrobiopterin (BH4), the necessary...

A patient with atypical phenylketonuria (defective BH2 synthesis), detected at age 6 months because of severe muscle hypotonia and serum phenylalanine of 20 mg/100 ml, had normal activities of phenylalanine-4-hydroxylase and DHPR in liver biopsy, but only 2% activity in the phenylalanine-4-hyroxylase in vivo test using deuterated phenylalanine. After IV administration of 2.5 mg/kg chemically pu...