Amino acids precursors

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 synthesis and metabolism of trace amines and monoamine neurotransmitters largely overlap [1]. The trace amines PEA, TYR and TRP are synthesized in neurons by decarboxylation of precursor amino acids through the enzyme aromatic amino acid decarboxylase (AADC). OCT is derived from TYR. by involvement of the enzyme dopamine (3-hydroxylase (Fig. 1 DBH). The catabolism of trace amines occurs in both glia and neurons and is predominantly mediated by monoamine oxidases (MAO-A and -B). While TYR., TRP and OCT show approximately equal affinities toward MAO-A and MAO-B, PEA serves as preferred substrate for MAO-B. The metabolites phenylacetic acid (PEA), hydroxyphenylacetic acid (TYR.), hydroxymandelic acid (OCT), and indole-3-acetic (TRP) are believed to be pharmacologically inactive. 

Trace Amines. Figure 1 The main routes of trace amine metabolism. The trace amines (3-phenylethylamine (PEA), p-tyramine (TYR), octopamine (OCT) and tryptamine (TRP), highlighted by white shading, are each generated from their respective precursor amino acids by decarboxylation. They are rapidly metabolized by monoamine oxidase (MAO) to the pharmacologically inactive carboxylic acids. To a limited extent trace amines are also A/-methylated to the corresponding secondary amines which are believed to be pharmacologically active. Abbreviations AADC, aromatic amino acid decarboxylase DBH, dopamine b-hydroxylase NMT, nonspecific A/-methyltransferase PNMT, phenylethanolamine A/-methyltransferase TH, tyrosine hydroxylase. 

These are four monoamines synthesized and seereted within many mammalian tissues, ineluding various regions in the brain, sympathetic nervous system, enlero-chromafhn cells of the digestive tract, and adrenal mednlla. These biogenic amines (indoleamine and catecholamines — dopamine, norepinephrine, and epinephrine) are synthesized within the cell from their precursor amino acids and have been associated with many physiological and behavioral functions in animals and humans. 

Celluloses (native or microcrystalline) are organic sorbents. They have a low specific surface area and are applied mainly in partition chromatography, especially for the separation of relatively polar compounds. Works on the topic include those by Whitton and coworkers [8], who examined biosynthetic pathways for the formation of taurine in vertebrates. Taurine and its precursor amino acids were extracted from tissues, and the purified supernatant was spotted onto cellulose plates. The... 

However, on a lightly cross-linked hydroxyethylmethacrylate/styrene polymer that swells in polar solvents (22, 365), or on a silica-gel support (366), catalyst performance matches that of the soluble one for the precursor amino acid substrates. A rhodium-DIOP analog has also been supported on a polymer containing pendent optically active alcohol sites [incidentally, formed via hydrosilylation and hydrolysis of a ketonic polymer component using an in situ rhodium(I)-DIOP catalyst]. The supported catalyst in alcohol again matched that of the soluble catalyst for... 

Glucosinolates are derived from amino acids. The precursor amino acids comprise seven protein amino acids (alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, and tryptophan), a number of chain-elongated methionines (CH3-S-(CH2)2-(CH2)n-CH(NH2)-COOH, n = 1-9), and chain-elongated... 

Tyrosine (Tyr or Y) (4-hydroxyphenylalanine ((5)-2-amino-3-(4-hydroxyphenyl)-propanoic acid)) is a polar, neutral, aromatic amino acid with the formula H00CCH(NH2)CH2C6H50H and is the precursor of thyroxin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and the pigment melanin. Being the precursor amino acid for the thyroid gland hormone thyroxin, a defect in this may result in hypothyroidism. Tyr is extremely soluble in water, a property that has proven useful in isolating this amino acid from protein hydrolysates. The occurrence of tyrosine- 0-sulfate as a constituent of human urine and fibrinogen has been reported. ... 

Martelli, A., Arlorio, M. and Tourn, M.L. (1993). Determination of amines and precursor amino acids in gorgonzola cheese by ion pair HPLC without derivation, Li Rivista di Scienza delValimentazione, 3, 261. 

Measurement of arteriovenous differences across the brain shows that it does take up the precursor amino acids for formation of the neurotransmitters including tryptophan and tyrosine. It also takes up the branched-chain amino acids for formation of glutamine. 

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. 

The neurotransmitter serotonin is derived from which precursor amino acid ... 

Meyer JS, Welch KM, Deshmukh VD Neurotransmitter precursor amino acids in the treatment of multi infarct dementia and Alzheimer s disease. J Am Geriatr Soc 25 289-298, 1977... 

T There is a relatively rare genetic disease in which the three branched-chain a-lceto acids (as well as their precursor amino acids, especially leucine) accumulate in the blood and spill over into the urine. This condition, called maple syrup urine disease because of the characteristic odor imparted to the urine by the a-lceto acids, results from a defective branched-chain a-lceto acid dehydrogenase complex. Untreated, the disease results in abnormal development of the brain, mental retardation, and death in early infancy. Treatment entails rigid control of the diet, limiting the intake of valine, isoleucine, and leucine to the minimum required to permit normal growth. ... 

Two types of pathways lead to nucleotides the de novo pathways and the salvage pathways. De novo synthesis of nucleotides begins with their metabolic precursors amino acids, ribose 5-phosphate, C02, and NH3. Salvage pathways recycle the free bases and nucleosides released from nucleic acid breakdown. Both types of... 

T Bauza, A Blaise, F Daumas, JC Cabanis. Determination of biogenic amines and their precursor amino acids in wines of the Vallee du Rhone by high-performance liquid chromatography with precolumn derivatization and fluorimetric detection. J Chromatogr A 707 373-379, 1995. 

FIGURE 8—16. Gamma-aminobutyric acid (GABA) is produced by synthesis from the precursor amino acid glutamate by the enzyme glutamic acid decarboxylase (Glu-AD). 

Nicotine.—The pyrrolidine ring of nicotine (6) derives from ornithine (1), label from, e.g., C-2 appearing equally spread over C-2 and C-5. This symmetrical incorporation of the precursor amino-acid is accounted for by the intermediacy of the symmetrical diamine putrescine (4), which is supported by other evidence too.1,2 The symmetrical incorporation of ornithine into nicotine (6) and into nornicotine (7) has been confirmed by the results4 of experiments with [2,3-13C2]ornithine [as (1)], thus reinforcing earlier 14C and 13C results (cf. Vol. 8, p. 5 Vol. 10, p. 14). Equal labelling of C-2, C-3 and of C-4, C-5 was observed. 

Pyrrolizidine Alkaloids.—The necic acid component of senecionine (8) derives from two molecules of isoleucine, radioactivity from precursor amino-acid being equally incorporated into both halves of the necic acid fragment, as shown in Scheme 2 (c/. Vol. 9, p. 4). It has now been shown that biotransformation of isoleucine into the necic acid involves loss of half of a tritium label from C-4 in each of the two amino-acid fragments.6 Removal of a proton is, therefore, stereospecific, and oxidation at C-4 does not proceed beyond the two-electron level i.e., a higher intermediate oxidation level, corresponding to a ketone, is excluded. Further results indicate that for each molecule of isoleucine it is the 4-pro-S proton [see (14)] which is lost. 

Banko et al. [11] speculated that the putative dual-enzyme process was instead catalyzed by a single, multifunctional enzyme. Their data clearly showed that in cell-free extracts of C. acremonium the rate of ACV synthesis was significantly greater when the precursor amino acids were provided than it was when AC and valine were used as substrates for the reaction [11], Jensen and her coworkers [12] demonstrated a similar result using cell-free extracts of S. clavuli-gerus. 

The 10 amino acids essential in the human diet (Arg, His, He, Leu, Lys, Met, Phe, Thr, Trp, Val) are synthesized by non-human organisms by multistep pathways starting from simple metabolic precursors. Amino acid biosynthesis is controlled by feedback inhibition and suppression of synthesis of biosynthetic enzymes. The ability of an amino acid analogue to block biosynthesis of the parent amino acid often contributes to the toxicity of the analogue. Mutants resistant to the toxic effects of the analogue can be valuable tools for studying various aspects of cellular mechanism (examples to be given below). 

Benzodiazepine Bases.—It is known that phenylalanine is an intact precursor for the benzodiazepine bases cyclopenin (124) and cyclopenol (125), via (122) and (123), in Penicillium cyclopium cultures.102 Examination of the stereochemical course of the necessary tritium loss from C-3 of the precursor amino-acid on formation of (124) has given a surprising result more than half of the tritium was... 

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