Phenylalanine hydroxylase and

The following is review on the molecular and physical properties of this class of monooxygenases, which are also known as hydroxylases. A typical monooxygenase reaction is the hydroxylation of an alkane to an alcohol which involves a reduced cosubstrate that reduces a second atom within the O2 molecule to form water. Flavin-containing monooxygenases include lysine oxygenase and 4-hydroxybenzoate hydroxylase. Reduced pteri-dines are involved in the phenylalanine hydroxylase and tryptophan hydroxylase reactions. See also Cytochrome P-450... 

This iron-dependent enzyme [EC 1.14.16.1], more widely known as phenylalanine hydroxylase and phenylalani-nase, catalyzes the reaction of L-phenylalanine with tetra-hydrobiopterin and dioxygen to produce L-tyrosine, di-hydrobiopterin, and water. 

Today aspartame is used in more than 6,000 food products. Aspartame is 160 times as sweet as sucrose based on mass equivalents. Approximately 16,000 tons are consumed annually on a global basis, with approximately 8,000 tons used in the United States and 2,500 tons in Europe. In the body aspartame is metabolized into its three components aspartic acid, phenylalanine, and methanol (Figure 11.1). Aspartic acid is a nonessential amino acid and phenylalanine is an essential amino acid. The condition called phenylketonuria (PKU) is a genetic disorder that occurs when a person lacks the enzyme phenylalanine hydroxylase and cannot process phenylalanine. This results in high phenylalanine blood levels that are metabolized into products one of these is phenylpyruvate, which contains a ketone group and... 

The reductant here is tetrahydrohiopterin, an electron carrier that has not been previously discussed and is derived from the cofactor biopterin. Because biopterin is synthesized in the body, it is not a vitamin. Tetrahydrohiopterin is initially formed by the reduction of dihydrobiopterin by NADPH in a reaction catalyzed by dihydrofolate reductase (Figure 23.28). NADH reduces the quinonoid form of dihydrobiopterin produced in the hydroxylation of phenylalanine back to tetrahydrohiopterin in a reaction catalyzed by dihydropteridine reductase. The sum of the reactions catalyzed by phenylalanine hydroxylase and dihydropteridine reductase is... 

F. Fusetti, H. Erlandsen, T. Flatmark, and R.C. Stevens. 1998. Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria J. Biol. Chem. 273 16962-16967. (PubMed)... 

In about 2% of cases, hyperphenylalaninemia is due to a deficiency of either biosynthesis or recycling of BH4, the cofactor of phenylalanine hydroxylase and related enzymes (see Figure 55-5). These infants could be diagnosed with PKU at first, but they deteriorate neurologically despite adequate dietary control. BH4 is a cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases. The latter two enzymes are involved in the synthesis of the neurotransmitters dopamine and serotonin, BH4 is also a cofactor for nitric... 

PKU can be caused by deficiencies in phenylalanine hydroxylase and by enzymes catalyzing the formation and regeneration of 5,6,7,8-tetrahydrobiopterin. How can this second defect cause the symptoms of PKU ... 

Figure 21.18 The phenylalanine hydroxylase and dihydropteridine reductase reactions. 

The pathway for the synthesis of serotonin from tryptophan is very similar to the pathway for the synthesis of norepinephrine from tyrosine (Fig. 48.7). The first enzyme of the pathway, tryptophan hydroxylase, uses an enzymic mechanism similar to that of tyrosine and phenylalanine hydroxylase and requires BH4 to hydroxylate the ring structure of tryptophan. The second step of the pathway is a decarboxylation reaction... 

The first evidences related to gene, nutrient, and disease interaction are emerged from single gene mutation originated metabolic diseases like phenylketonuria. Phenylketonuria is an inborn error of metabolism resulting from a deficiency of phenylalanine hydroxylase and characterized by mental retardation and is treatable by a low phenylalanine diet [71]. 

Fig. 1.2 A short segment of the gene for phenylalanine hydroxylase and the amino acid sequence of the protein generated from the gene. The successive triplet letter codons specify which amino acid is to be incorporated...

Classic PKU Classic PKU is an autosomal recessive disease due to deficiency of phenylalanine hydroxylase and is treated with a low phenylalanine diet. Since phenylalanine is present in most food, dietary management is not easy, especially for a growing child. However, conscientious compliance is rewarded with a lifetime of normal achievement (Fig. 48.2). 

Both the absence of phenylalanine hydroxylase and the block of the 5-hydroxytryptophan decarboxylase could account for the low plasma and brain serotonin observed in patients with phenylketonuria. 

Fusetti F, Erlandsen H, Flatmark T, Stevens RC. Structure of Tetrameric Human Phenylalanine Hydroxylase and Its Implications For Phenylketonuria. J Biol Chem 1998 273(27) 16962-16967. 

Sidney Velick to amino acid metabolism. By 19561 had become heavily involved in hydroxyl-ation mechanisms, having discovered tryptophan hydroxylase, phenylalanine hydroxylase, and tyrosine hydroxylase and having purified and studied the last two enzymes. 

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