3-Hydroxy-a-methyl-L-tyrosine

Therapeutic Function Antihypertensive Chemical Name 3 hydroxy-a-methyl-L-tyrosine Common Name L-0 -methyl-3,4-dihvdroxyphenvlalanine Structural Formula oh... 

RN 2544-09-4 MF C,2H,7N04 MW 239.27 EINECS 219-821-2 CN 3-hydroxy-a-methyl-L-tyrosine ethyl ester... 

Synonyms. 3-Hydroxy-a-methyl-L-tyrosine L-3-(3, 4-dihydrox3rphenyl)-2-methylalanine a-Methyldopa L-2-amino-2-methyl-3-(3, 4-dihydrox3rphenyl) propionic acid ... 

Synonyma 3-Hydroxy-a-methyl-L-tyrosine ethyl eater... 

L-3-(3, 4-Dihydroxyphenyl)-2-methylalanine sesquihydrate L-Tyrosine, 3-hydroxy-a-methyl-, sesquihydrate BP USP ... 

Dopamine may alternatively be formed from tyrosine via hydroxylation of L-dopa which is decarboxylated. However, inverse isotope dilution experiments to study the formation of dopamine and dopa have shown that this is probably a minor pathway in peyote (176). It has been shown that L-tyrosine is incorporated into alkaloids in peyote three times more efficiently than into protein (344). 4-Hydroxy-3-methoxyphenethylamine can be methylated to 3,4-dimethoxy-phenethylamine (homoveratrylamine), which may be viewed as a dead-end product in Scheme 2 (10, 203). Phenylalanine is probably not a precursor of the... 

SYNTHESIS, STORAGE, AND RELEASE OF CATECHOLAMINES Synthesis—The steps in the synthesis of DA, NE (known outside the U.S. as noradrenaline), and Epi (known as adrenahne) are shown in Eigure 6-A. Tyrosine is sequentially 3-hydroxylated and decarboxylated to form DA. DA is 3-hydroxylated to yield NE (the transmitter in postganglionic nerves of the sympathetic branch of the ANS), which is N-methylated in chromaffin tissue to give Epi. The enzymes involved are not completely specific consequently, other endogenous substances and some drugs are also substrates. 5-hydroxytryptamine (5-HT, serotonin) can be produced from 5-hydroxy-L-tryptophan by aromatic L-amino acid decarboxylase (AAD or dopa decarboxylase). AAD also converts dopa into DA, and methyldopa to a-methyl-DA, which is converted to a-methyl-NE by dopamine /3-hydroxylase (Dj3H Table 6-4). 

The difficulties which may be encountered in establishing well-known pathways in a new plant are illustrated by feeding experiments with [2 - " C]tyrosine, [l, 2 - H2]dopamine, and 3-hydroxy-4-methoxy[ar- H]phenylethylamine in E. merkei The conversion of tyrosine into hordenine (63), established in barley could not be demonstrated. Nor were tyrosine and dopamine incorporated into salsoline (55), but all three of the labelled compounds were converted into 3,4-dimethoxyphenylethylamine. These results were rationalized as indicating a pathway that diverged after dopamine with appropriate methylation, giving either salsoline (55) or 3,4-dimethoxyphenylethylamine (a similar branch point is observed in L. williamsii for the biosynthesis of mescaline and tetrahydroiso-quinolines). Further, at the time of the experiments the required methyl-transferases for salsoline and hordenine biosynthesis were apparently blocked. In any event the pathway to 3,4-dimethoxyphenylethylamine is manifestly the dominant one, as this alkaloid and its iV-methyl derivatives are major constituent bases of this plant. 

Some properties of purified endo-(l- -4)- 3-D-xylanase from the ligniperdous fungus Trametes hirsuta have been investigated. The enzyme was stable between pH 4.0 and 8.0 with optimum activity at pH 5.0-5.5. The temperature optimum was 50 C and the enzyme was stable for up to 30 min at 45 C however, it was denatured at higher temperatures. The for 4-0-methyl-D-glucurono-D-xylan was 6.36 X10" equivalents of D-xylose per litre, the activation energy was 28 kj moF The enzyme (mol. wt. 2.2-2.4X 10 by gel chromatography) was activated by Ca " and inhibited by Ag and Hg. On the basis of the effects of 2-hydroxy-5-nitrobenzyl bromide, iV-bromosuccinimide, and A-acetylimidazole it was assumed that L-tryptophan and possibly L-tyrosine residues influence the enzyme catalysts. 

Ala = Alanine, 6-Br-Trp = 6-bromotryptophan, Dide-Phe = a,P-dide-hydro-3,4,5-trihydroxyphenylalanine, Dide-Val = a,P-didehydro-valine, diOH-Sty = 3,4-dihydroxy-trans-styrylamine = [( )-l-amino-2-(3,4-dih-ydroxyphenyl)ethene], Gly = Glycine, lieu = Isoleucine, Leu = Leucine, N-Me = A-methyl, N,N-diMe = A,A-dimethyl-, P-OH = P-hydroxy, OH-Sty = 4-hydroxy-tra s-styrylamine = [( )-l-amino-2-(4-hydroxypheny-l)ethene], Phe = Phenylalanine, Phe-Et = Phenylethylamine, Pro= Proline, Sty = Styrylamine, Trp = Tryptophan, Tyr = Tyrosine, Val = Valine. 

The biosynthetic work on mescaline in the peyote cactus L. williamsii and in the Peruvian cactus T. pachanoi has led to the formulation of biosynthetic pathways according to Scheme 2. A major pathway probably involves decarboxylation of tyrosine followed by hydroxylation to yield dopamine. Dopamine is methylated on the meta hydroxy group to 4-hydroxy-3-methoxyphenethylamine (3-methoxytyramine) which then undergoes hydroxylation to the key intermediate 4,5-dihydroxy-3-methoxyphenethylamine (20). Para-O-methylation of 20 yields 3,4-dimethoxy-5-hydroxyphenethylamine (21), which is the immediate precursor of the main phenolic tetrahydroisoquinolines of peyote. Alternatively, meta-O-methylation yields 3,5-dimethoxy-4-hydroxyphenethylamine (19), which is further efficiently methylated to mescaline. Parallel pathways involving N-methylated compounds probably exist in these cacti (10). 

The following were administered separately to P. cyclopium [carboxyl- and [ N]-anthranilic acid, phenylalanine with labels at positions 1,2, and 3, and also N-labelled phenylalanine and [methyl- C]methiomne. The results show an intact incorporation of all the atoms of phenylalanine and anthranilic acid into both (49) and (50), with L-phenylalanine preferred over the D-isomer. The iV-methyl group originates from the S-methyl group of methionine. The cyclic dipeptide formed from these two amino-acids is presumably an intermediate on the pathway to the alkaloids. As phenylalanine serves as a precursor for cyclopenol, the origin of the hydroxy-group is by meta-hydroxylation of phenylalanine. Further, m-tyrosine and tyrosine are only unspecific precursors. 

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