Amino acid tyrosine

Amino acid-derived hormones include the catecholamines, epinephrine and norepinephrine (qv), and the thyroid hormones, thyroxine and triiodothyronine (see Thyroid AND ANTITHYROID PREPARATIONS). Catecholamines are synthesized from the amino acid tyrosine by a series of enzymatic reactions that include hydroxylations, decarboxylations, and methylations. Thyroid hormones also are derived from tyrosine iodination of the tyrosine residues on a large protein backbone results in the production of active hormone. 

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). 

As noted previously in Section 11.10, biological dehydrations are also common and usually occur by an ElcB mechanism on a substrate in which the -OH group is two carbons away from a carbonyl group. An example occurs in the biosynthesis of the aromatic amino acid tyrosine. A base first abstracts a proton from the carbon adjacent to the carbonyl group, and the anion intermediate... 

Using curved arrows, propose a mechanism for the following reaction, one of the steps in the biosynthesis of the amino acid tyrosine. 

The amino acid tyrosine is biologically degraded by a series of steps that include the following transformations ... 

Together with dopamine, adrenaline and noradrenaline belong to the endogenous catecholamines that are synthesized from the precursor amino acid tyrosine (Fig. 1). In the first biosynthetic step, tyrosine hydroxylase generates l-DOPA which is further converted to dopamine by the aromatic L-amino acid decarboxylase ( Dopa decarboxylase). Dopamine is transported from the cytosol into synaptic vesicles by a vesicular monoamine transporter. In sympathetic nerves, vesicular dopamine (3-hydroxylase generates the neurotransmitter noradrenaline. In chromaffin cells of the adrenal medulla, approximately 80% of the noradrenaline is further converted into adrenaline by the enzyme phenylethanolamine-A-methyltransferase. 

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. 

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... 

Figure 8.5 The synthetic pathway for noradrenaline. The hydroxylation of the amino acid, tyrosine, which forms dihydroxyphenylalanine (DOPA) is the rate-limiting step. Conversion of dopamine to noradrenaline is effected by the vesicular enzyme, dopamine-P-hydroxylase (DpH) after uptake of dopamine into the vesicles from the cell cytosol...

Enzyme electrodes for the amino acids tyrosine and lysine have been... 

The most potent thrombin inhibitor is hirudin, originally isolated from the salivary glands of the medicinal leech Hirudo medicinalis. Its inhibition constant is in the femtomolar (10-15 M) range (57). It is a 65-amino-acid tyrosine-sulfated single-chain polypeptide. Recombinant hirudin differs from native hirudin by the absence of the sulfate group on tyrosine 63 (Tyr-63) and is referred to as desulfato hirudin. The loss of this sulfate group reduces the thrombin inhibitory potency by 10-fold. 

Drosophila DDC belongs to a family of pyridoxal-dependent decarboxylases that extends from prokaryotes to eukaryotic plants and animals. The members of this family show significant sequence similarity over much of their length, even though the individual proteins have quite different substrate specificities, including the amino acids tyrosine, tryptophan, phenylalanine, histidine, and glutamate, and the amino acid derivatives... 

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-... 

FIGURE 7.5 Structural domains of LHCII xanthophylls. Aromatic amino acids tyrosine in the neoxanthin domain and tryptophan and phenylalanine in the violaxanthin domain are labeled as Y, W, and F, respectively. 

Derived from the amino acid tyrosine, thyroid hormones are unique because they contain iodine. At this time, its incorporation into thyroid hormones is the only known use for iodine in the body. There are two thyroid hormones, named for the number of iodides added to the tyrosine residues of the thyroglobulin triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine). Although significantly more T4 is synthesized by the thyroid gland, T3 is the active hormone. At the target tissue, T4 is deiodoninated to form the more potent T3. 

It appears as if an axiom of stereochemistry, the absolute identity of the most important chemical and physical properties of chiral isomers, is no longer valid. Experiments using the amino acid tyrosine (Tyr) showed unexpected differences in the solubility of D-and L-Tyr in water a supersaturated solution of 10 mM L-Tyr crystallised much more slowly than that of D-Tyr under the same conditions. The saturated solution of L-Tyr was more concentrated than that of D-Tyr. Supersaturated solutions of DL-Tyr in water formed precipitates containing mainly D-Tyr and DL-Tyr, so that there was an excess of L-Tyr in the saturated solution. The experiments were carried out with extremely great care in order to exclude the possibility of contamination. Further experiments will show whether this is a particular property of tyrosine, or whether other amino acids will show similar behaviour. Possible... 

Detection and quantification of protein by measuring absorbency at 280 nm is perhaps the simplest such method. This approach is based on the fact that the side chains of the amino acids tyrosine and tryptophan absorb at this wavelength. The method is popular, as it is fast, easy to perform and is non-destructive to the sample. However, it is a relatively insensitive technique, and identical concentrations of different proteins will yield different absorbance values if their content of tyrosine and tryptophan vary to any significant extent. Hence, this method is rarely used to determine the protein concentration of the final product, but it is routinely used during downstream processing to detect protein elution off chromatographic columns, and hence track the purification process. 

In microsomes from Sinapis alba L.,33,34 Tropaeolum majus L.,35,36 and Carica papaya L.,37 the aromatic amino acids (tyrosine and phenylalanine) have been shown to be converted to the corresponding oximes by cytochrome P450-dependent monooxygenases. The conversion of tyrosine to the corresponding oxime in microsomes from S. alba was approximately 1000 fold lower than in microsomes from the cyanogenic sorghum.33 This made a biochemical approach for the isolation... 

Melanin is a complicated mixture of optically absorbing materials. chromophores), of which melanin is the most important. Melanin is a complicated mixture of optically absorbing materials, formed as an end product during the photo-assisted metabolism of the amino acid tyrosine. Both are bound covalently to the surrounding proteins within the skin, and other pigmented regions of the body. 

Tyramine (4-hydroxy-phenethylamine, para-tyramine, / -tyramine) A phenolic amine CgHnNO, a monoamine compound derived from the amino acid tyrosine. 

The fluorimetric methods often offer improved specificity and sensitivity over colorimetric procedures and the quantitative assays for the aromatic amino acids tyrosine and phenylalanine illustrate this point. 

Two amino acids, tyrosine and arginine are of particular importance as precursors of signalling molecules. As outlined in Figure 4.3, tyrosine is the amino acid precursor of thyroid hormones tri-iodothyronine (T3) and tetra-iodothyronine (T4) and also of catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine). 

In addition to their well known role in protein structure, amino acids also act as precursors to a number of other important biological molecules. For example, the synthesis of haem (see also Section 5.3.1), which occurs in, among other tissues, the liver begins with glycine and succinyl-CoA. The amino acid tyrosine which maybe produced in the liver from metabolism of phenylalanine is the precursor of thyroid hormones, melanin, adrenaline (epinephrine), noradrenaline (norepinephrine) and dopamine. The biosynthesis of some of these signalling molecules is described in Section 4.4. 

In the genetic code of human nuclear DNA, one of the codons specifying the amino acid tyrosine is UAC. Another codon specifying this same amino acid is ... 

Note that these structures are related to that for the amino acid tyrosine, from which they are derived. The adrenal glands, small pieces of tissue that ride on top of the kidneys, secrete these hormones. When they activate adrenergic receptors on the surface of muscle cells, adenylate cyclase is activated, increased cAMP results, and the cascade of events in muscle cells is started (figure 17.1). 

The pathways for synthesis of the monoamine neurotransmitters are not, at least in some neurones, saturated with precursor amino acids (tyrosine for formation of noradrenaline plus dopamine tryptophan for formation of 5-hydroxytryptamine (serotonin)). Marked increases in the blood level of these amino acids can increase their concentrations in neurones which can influence the concentration of the respective neurotransmitters in some neurones in the brain. This may result in changes in behaviour. 

Do appreciate that there is no strict convention for how you orientate the structure on paper. In fact, we will turn structures around, as appropriate, to suit our needs. For example, the amino acid tyrosine has three functional groups, i.e. a carboxylic acid, a primary amine, and a phenol. How we draw tyrosine will... 

Thyroxine is actually a simple derivative of the aromatic amino acid tyrosine (see Section 13.1), but is believed to be derived by degradation of a larger protein molecule containing tyrosine residues. One hypothesis for their formation invokes suitably placed tyrosine residues in the protein thyroglobulin being iodinated to di-iodotyrosine. These residues then react together by phenolic oxidative coupling. 

The thyroid hormone thyroxine (tetraiodo-thyronine, T4) and its active form triiodothyronine (T3) are derived from the amino acid tyrosine. The iodine atoms at positions 3 and 5 of the two phenol rings are characteristic of them. Post-translational synthesis of thyroxine takes place in the thyroid gland from tyrosine residues of the protein thyro-globulin, from which it is proteolytically cleaved before being released, iodothyronines are the only organic molecules in the animal organism that contain iodine. They increase the basal metabolic rate, partly by regulating mitochondrial ATP synthesis, in addition, they promote embryonic development. 

Feruloylated pectins have been found in the parenchymatous cell walls of many Dicotyledons (mainly in the Centrospermae and Solanaceae), but UV-fluorescence microscopy suggests that at least the epidermal cell walls of all Dicotyledons contain phenolic residues it remains to be seen whether these phenolic residues are attached to polysaccharides or to cutin, but location of even a small quantity of, say, feruloyl-pectin in the epidermal wall would be particularly significant in the control of growth because the extensibility of the epidermis controls the expansion of whole stems (23) and leaves (Fry, unpublished observations). The extensins, as already mentioned, are rich in the phenolic amino acid tyrosine (2). 

Cresols can enter your body tissues quickly if you breathe air containing cresol gas or mist (droplets of cresol-containing liquid in the air), drink water or eat food that contains cresols, or allow your skin to come into contact with substances that contain cresols. If you live near a hazardous waste site, you might come into contact with cresols by drinking water, touching substances, or breathing in air that contains cresols. Cresols may also be formed in your body from other compounds, such as toluene and the amino acid tyrosine, which is present in most proteins. Most of the cresols that enter your body are quickly changed to other substances and leave your body in the urine within 1 day. More information on how cresols enter and leave your body can be found in Chapter 2. 

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