Tyrosine amino acid synthesis

Herbicides also inhibit 5- (9/-pymvylshikiniate synthase, a susceptible en2yme in the pathway to the aromatic amino acids, phenylalanine, tyrosine and tryptophan, and to the phenylpropanes. Acetolactate synthase, or acetohydroxy acid synthase, a key en2yme in the synthesis of the branched-chain amino acids isoleucine and valine, is also sensitive to some herbicides. Glyphosate (26), the sulfonylureas (136), and the imida2oles (137) all inhibit specific en2ymes in amino acid synthesis pathways. 

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. 

Another hypothesis of aromatic amino acid synthesis, based on the distribution of the label in tyrosine of yeast grown on radioactive pyruvate or acetate, is that it involves the cyclic condensation of two unsym-metric 4-carbon acids, e.g., oxalacetate. The side chain of tyrosine appears to be formed from pyruvate as an intact 3-carbon unit. 

Pish protein concentrate and soy protein concentrate have been used to prepare a low phenylalanine, high tyrosine peptide for use with phenylketonuria patients (150). The process includes pepsin hydrolysis at pH 1.5 ptonase hydrolysis at pH 6.5 to Hberate aromatic amino acids gel filtration on Sephadex G-15 to remove aromatic amino acids incubation with papain and ethyl esters of L-tyrosine and L-tryptophan, ie, plastein synthesis and ultrafiltration (qv). The plastein has a bland taste and odor and does not contain free amino acids. Yields of 69.3 and 60.9% from PPG and soy protein concentrate, respectively, have been attained. 

Catecholamine biosynthesis begins with the uptake of the amino acid tyrosine into the sympathetic neuronal cytoplasm, and conversion to DOPA by tyrosine hydroxylase. This enzyme is highly localized to the adrenal medulla, sympathetic nerves, and central adrenergic and dopaminergic nerves. Tyrosine hydroxylase activity is subject to feedback inhibition by its products DOPA, NE, and DA, and is the rate-limiting step in catecholamine synthesis the enzyme can be blocked by the competitive inhibitor a-methyl-/)-tyrosine (31). 

The Dim ester was developed for the protection of the carboxyl function during peptide synthesis. It is prepared by transesterification of amino acid methyl esters with 2-(hydroxymethyl)-l,3-dithiane and Al(/-PrO)3 (reflux, 4 h, 75°, 12 torr, 75% yield). It is removed by oxidation [H2O2, (NH4)2Mo04 pH 8, H2O, 60 min, 83% yield]. Since it must be removed by oxidation it is not compatible with.sulfur-containing amino acids such as cysteine and methionine. Its suitability for other, easily oxidized amino acids (e.g., tyrosine and tryptophan) must also be questioned. It is stable to CF3CO2H and HCl/ether. - ... 

This led to the conclusion that these amino acids were essential for the resolution capability and only 6 new libraries of 18 compounds had to be synthesized with these amino acid residues to define the position 3. Surprisingly, the separation abilities of all six libraries were very similar. Therefore, tyrosine was chosen for continuing deconvolution, since it is convenient as its aromatic ring can easily be detected by UV spectrometry. The last step, defining position 5, required the synthesis and testing of 6 individual hexapeptides. 

Auxotrophic mutant lack one or more enzymes involved in the synthesis of amino acids (such as tyrosine). This prevents accumulation of the amino acid and thus avoids feedback inhibition of enzymatic steps in the L-phenylalanine pathway. 

The amino acid tyrosine is the starting point in the synthesis of the catecholamines and of the thyroid hormones tetraiodothyronine (thyroxine T4) and triiodothyronine (T3) (Figure 42-2). T3 and T4 are unique in that they require the addition of iodine (as T) for bioactivity. Because dietary iodine is very scarce in many parts of the world, an intricate mechanism for accumulating and retaining T has evolved. 

By contrast, the cytoplasmic decarboxylation of dopa to dopamine by the enzyme dopa decarboxylase is about 100 times more rapid (Am 4x 10 " M) than its synthesis and indeed it is difficult to detect endogenous dopa in the CNS. This enzyme, which requires pyridoxal phosphate (vitamin B6) as co-factor, can decarboxylate other amino acids (e.g. tryptophan and tyrosine) and in view of its low substrate specificity is known as a general L-aromatic amino-acid decarboxylase. 

The pathway for synthesis of the catecholamines dopamine, noradrenaline and adrenaline, illustrated in Fig. 8.5, was first proposed by Hermann Blaschko in 1939 but was not confirmed until 30 years later. The amino acid /-tyrosine is the primary substrate for this pathway and its hydroxylation, by tyrosine hydroxylase (TH), to /-dihydroxyphenylalanine (/-DOPA) is followed by decarboxylation to form dopamine. These two steps take place in the cytoplasm of catecholaminereleasing neurons. Dopamine is then transported into the storage vesicles where the vesicle-bound enzyme, dopamine-p-hydroxylase (DpH), converts it to noradrenaline (see also Fig. 8.4). It is possible that /-phenylalanine can act as an alternative substrate for the pathway, being converted first to m-tyrosine and then to /-DOPA. TH can bring about both these reactions but the extent to which this happens in vivo is uncertain. In all catecholamine-releasing neurons, transmitter synthesis in the terminals greatly exceeds that in the cell bodies or axons and so it can be inferred... 

The first step in the synthesis of 5-HT is hydroxylation of the essential amino acid, tryptophan, by the enzyme tryptophan hydroxylase (Fig. 9.4). This enzyme has several features in common with tyrosine hydroxylase, which converts tyrosine to /-DOPA in... 

Figure 13.7 Synthesis and structure of the trace amines phenylethylamine, /)-tyramine and tryptamine. These are all formed by decarboxylation rather than hydroxylation of the precursors of the established monoamine neurotransmitters, dopamine and 5-HT. (1) Decarboxylation by aromatic L-amino acid decarboxylase (2) phenylaline hydroxylase (3) tyrosine hydroxylase (4) tryptophan hydroxylase...

Phenoxazines — The two main types of phenoxazines are the ommochromes and the microbial phenoxazines. The biosynthesis of ommochromes occurs via the kynurenine pathway. The tryptophan amino acid is converted to formylkynurenine and then to kynurenine and 3-hydroxykynurenine. Not all the steps of ommochrome synthesis are completely elucidated yet. Ommatins are dimers and ommins are oligomers of 3-hydroxykynurenine. - The papiliochromes are derived from tyrosine as well as from the tryptophan pathway. The key intermediate in the formation of papiliochromes is N-beta-alanyldopamine (NBAD). Papiliochromes are synthesized in special wing scale cells, before melanins. " "... 

A polynucleoside with an unnatural polymeric backbone was synthesized by SBP-catalyzed oxidative polymerization of thymidine 5 -p-hydroxyphenylacetate. Chemoenzymafic synthesis of a new class of poly(amino acid), poly(tyrosine) containing no peptide bonds, was achieved by the peroxidase-catalyzed oxidative polymerization of tyrosine ethyl esters, followed by alkaline hydrolysis. Amphiphile higher alkyl ester derivatives were also polymerized in... 

In an attempt to identify new, biocompatible diphenols for the synthesis of polyiminocarbonates and polycarbonates, we considered derivatives of tyrosine dipeptide as potential monomers. Our experimental rationale was based on the assumption that a diphenol derived from natural amino acids may be less toxic than many of the industrial diphenols. After protection of the amino and carboxylic acid groups, we expected the dipeptide to be chemically equivalent to conventional diphenols. In preliminary studies (14) this hypothesis was confirmed by the successful preparation of poly(Z-Tyr-Tyr-Et iminocarbonate) from the protected tyrosine dipeptide Z-Tyr-Tyr-Et (Figure 3). Unfortunately, poly (Z-Tyr-Tyr-Et iminocarbonate) was an insoluble, nonprocessible material for which no practical applications could be identified. This result illustrated the difficulty of balancing the requirement for biocompatibility with the need to obtain a material with suitable "engineering" properties. 

The pathway of melanin synthesis starts from the amino acid tyrosine (Fig. 1). The first two reactions are catalyzed by the copper-containing enzyme tyrosinase (EC 1.14.18.1). Tyrosine is hydroxylated to 3,4-dihy-... 

Synthesis Synthesized on demand derived from cholesterol Synthesized in advance derived from amino acids Synthesized in advance stored as part of thyroglobulin Synthesized in advance derived from tyrosine... 

Precursors of phenylpropanoids are synthesized from two basic pathways the shikimic acid pathway and the malonic pathway (see Fig. 3.1). The shikimic acid pathway produces most plant phenolics, whereas the malonic pathway, which is an important source of phenolics in fungi and bacteria, is less significant in higher plants. The shikimate pathway converts simple carbohydrate precursors into the amino acids phenylalanine and tyrosine. The synthesis of an intermediate in this pathway, shikimic acid, is blocked by the broad-spectrum herbicide glyphosate (i.e., Roundup). Because animals do not possess this synthetic pathway, they have no way to synthesize the three aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), which are therefore essential nutrients in animal diets. 

Many secondary phenolic compounds are derived from the amino acids phenylalanine and tyrosine and therefore contain an aromatic ring and a three-carbon side chain (see Fig. 3.3). Phenylalanine is the primary substrate for phenylpropanoid synthesis in most higher vascular plants, with tyrosine being used to a lesser extent in some plants. Because of their common structure, compounds derived from these amino acids are collectively called phenylpropanoids. 

Dopamine synthesis in dopaminergic terminals (Fig. 46-3) requires tyrosine hydroxylase (TH) which, in the presence of iron and tetrahydropteridine, oxidizes tyrosine to 3,4-dihydroxyphenylalanine (levodopa.l-DOPA). Levodopa is decarboxylated to dopamine by aromatic amino acid decarboxylase (AADC), an enzyme which requires pyri-doxyl phosphate as a coenzyme (see also in Ch. 12). 

Consider one small molecule, phenylalanine. It is an essential amino acid in our diet and is important in protein synthesis (a component of protein), as well as a precursor to tyrosine and neurotransmitters. Phenylalanine is one of several amino acids that are measured in a variety of clinical methods, which include immunoassay, fluorometry, high performance liquid chromatography (HPLC see Section 4.1.2) and most recently MS/MS (see Chapter 3). Historically, screening labs utilized immunoassays or fluorimetric analysis. Diagnostic metabolic labs used the amino acid analyzer, which was a form of HPLC. Most recently, the tandem mass spectrometer has been used extensively in screening labs to analyze amino acids or in diagnostic labs as a universal detector for GC and LC techniques. Why did MS/MS replace older technological systems The answer to this question lies in the power of mass spectrometer. 

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