Tyrosine from phenylalanine

As constituents of proteins the amino-acids are important constituents of the food of animals. Certain amino-acids can be made in the body from ammonia and non-nitrogenous sources others can be made from other amino-acids, e.g. tyrosine from phenylalanine and cystine from methionine, but many are essential ingredients of the diet. The list of essential amino-acids depends partly on the species. See also peptides and proteins. 

Two amino acids—cysteine and tyrosine—can be synthesized in the body, but only from essential amino acid ptecutsots (cysteine from methionine and tyrosine from phenylalanine). The dietary intakes of cysteine and tytosine thus affect the requirements for methionine and phenylalanine. The remaining 11 amino acids in proteins are considered to be nonessential or dispensable, since they can be synthesized as long as there is enough total protein in the diet—ie, if one of these amino acids is omitted from the diet, nitrogen balance can stiU be maintained. Howevet, only three amino acids—alanine, aspartate, and glutamate—can be considered to be truly dispensable they ate synthesized from common metabolic intetmediates (pyruvate, ox-... 

This was decided in 1882 by Erlenmeyer and Lipp who synthesised tyrosine from phenylalanine. Their first method to prepare p-sulpho-... 

Figure 9-6. Synthesis of tyrosine from phenylalanine. Hydroxylation of phenylalanine to tyrosine is one of several reactions in the body that require tetrahydrobiopterin as a cofactor to provide electrons and hydrogen as reducing equivalents.

Many biologically important routes of amino acid utilization, other than those leading to incorporation into proteins, are known. Some of these routes are distinctly anabolic pathways in which the amino acids serve as an initial substrate in an independent biosynthetic pathway. Other simple pathways involve the conversion of one amino acid to another, such as the formation of tyrosine from phenylalanine. The utilization of glycine in the formation of porphyrin derivatives occurs by very complex highly branched pathways. Some other biologically important pathways lead to the biosynthesis of small peptides as in the biosynthesis of glutathione. 

Phenylalanine hydroxylase from rat liver contains a tightly bound non-heme iron that is essential for the activity of the enzyme. The enzyme functions aerobically to produce tyrosine from phenylalanine and a tetrahydropterin.828... 

It was mentioned above that in aromatic hydroxylation an oxidant is required, and the product yields vary considerably with the oxidant used (for the reason why 02 does not serve as a typical one-electron oxidant, see Chap. 8). A typical example is the formation of tyrosines from phenylalanine (Table 3.4). Their yields are especially low in the absence of an oxidant, since dimerization usually dominates over disproportionation in these systems. The determination of the products is usually done by either HPLC or GC/MS after trimethylsilylation, and the proteins have to be hydrolyzed prior to analysis. Attention has been drawn to the fact that in vivo cytochrome P-450 enzymes hydroxylate phenylalanine to p-tyrosine (Bailey et al. 1997). 

Note that these reactions can also be used to synthesize tyrosine from phenylalanine. 

Of the 20 amino acids in proteins, the body can readily synthesize eight if an appropriate nitrogen source is available. Two others can be synthesized from other amino acids of the diet tyrosine from phenylalanine and cysteine from methionine. The rest must be provided in the diet (Chapter 17), since the body can synthesize none or an insufficient amount. The dietary requirement depends on several factors. Beside essential amino acids, the diet should provide the nitrogen required for synthesis of the nonessential amino acids. 

Individuals with PKU lack phenylalanine hydroxylase (pheny-lalanine-4-monooxygenase) activity so they cannot synthesize tyrosine from phenylalanine. Tyrosine is therefore an essential amino acid for these patients. 

Animals - Animal cells do not synthesize aromatic rings. linstead, animal cells extensively modify amino acids with aromatic rings. Examples include the synthesis of tyrosine from phenylalanine, the synthesis of pigments and hormones from tyrosine, and the use of tyrosine, tryptophan, and histidine in synthesis of biogenic amines - compounds that serve as hormones and neurotransmitters. 

Chorismate is an intermediate in the biosynthesis of the aromatic amino acids tryptophan, phenylalanine, and tyrosine. Mammals do not synthesize these amino acids bom chorismate. Instead, they obtain the essential aromatic amino acids tryptophan and phenylalanine from the diet, and they can synthesize tyrosine from phenylalanine. Glyphosate is an effective herbicide because it prevents synthesis of aromatic amino acids in plants. But the compound has no effect on mammals because they have no active pathway for de novo aromatic amino acid synthesis. 

The aromatic amino acids cannot be synthesized directly by the vertebrate organism. The vertebrates can form tyrosine from phenylalanine. ... 

A number of cyanogenic glycosides are derived from the aromatic amino acids phenylalanine and tyrosine. From phenylalanine is derived the epimeric pair of fl-glucosides known as (J()-pmnasin and (S)-sambunigrin. (J )-Passieduhn of purple passion fruit, also known as purple granadilla (Passiflora edulis, Passifloraceae),... 

The formation of the amino acids tyrosine from phenylalanine and glutamic acid from histidine. 

One of the first important derivatives of phenylpyruvic acid is the essential amino-acid phenylalanine, produced with the aid of pyridoxamine (Figure 2.17, with that reaction running in reverse). It is an essential amino-acid because all animals must have it in their diet. Tyrosine in plants is made directly from prephenic acid by oxidation concurrently with decarboxylation. Mammals can make tyrosine from phenylalanine, but insects must obtain it in food. Some other simple phenyl-Cj compounds and derivatives are shown in Figure 8.2. 

Although the formation of tyrosine from phenylalanine has been demonstrated in vitro as early as 1913 (Embden and Baldes), it is only recently that any progress has been made in describing the enzyme system which catalyzes the reaction. In 1952, Udenfriend and Cooper (1952a) reported that soluble extracts prepared from rat liver could catalyze the hydroxylation of phenylalanine. The reaction was reported to be stimulated by DPN and a variety of alcohols and aldehydes. In 1956, it was shown by Mitoma that DPNH could replace the DPN and alcohol (or aldehyde). It was also reported that the rat liver extracts could be fractionated into two crude protein fractions, both of which were required for full enzyme activity. The extreme lability of one of these fractions hampered attempts to further define the components of the system. 

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