Histidine and derivatives

Although analyses for histidine after acid hydrolysis are usually satisfactory, the values found may be slightly low, particularly after chemical modification of other residues. This has often led to estimates of the number of residues in a protein that are too high, when histidine has been used to calculate a one-residue value. 

Naturally-occurring derivatives of histidine (methylhistidines and phosphohistidines) are described in 2.12.2. The carboxymethyl-histidines are the best characterized derivatives of histidine formed in proteins in vitro. 

Nitrogens 1 and 3 in the imidazole ring of histidyl residues in proteins may be alkylated with iodoacetic acid (generally in a much slower reaction than alkylation of cysteinyl residues) to give three carboxy-methyl derivatives 1-carboxymethylhistidine, 3-carboxymethyl-histidine and 1,3-dicarboxymethylhistidine ( 3.4). In general, the 3-carboxymethyl derivative is formed most rapidly. These derivatives are stable to acid hydrolysis under the usual conditions (but excess reagent must be removed) and may be analyzed on the long column of most analyzers as described below. 

Using the 150 cm column of Spademan et al. (1958), Crestfield et al. (1963) showed that 1,3-dicarboxymethylhistidine elutes about 55 ml before aspartic acid (124 ml), 1-carboxymethylhistidine elutes about 9 ml after glutamic acid (177 ml) and 6 ml before proline (193 ml), and 3-carboxymethylhistidine elutes about 16 ml after alanine (264 ml). The color values of the dicarboxymethyl- and monocarboxymethyl-derivatives were determined as 96 % and 99 % that of serine respectively, and 97% and 100% that of glycine respectively. 

The dicarboxymethyl derivative has been characterized in electrophoretic and chromatographic systems, and all three derivatives were separated by ion exchange chromatography in pyridine-formic acid buffer at pH 3.25 (Banaszak and Gurd 1964). 

---

Annular tautomerism of azoles and benzazoles [the nonaromatic tautomers of imidazole 17, 2H and 4(5)H have been calculated at the MP2/6-31G level to be about 15 kcal mol less stable than the IH tautomer (95JOC2865)]. We present here the case of 4(5)-substituted imidazoles, different from the histamine, histidine, and derivatives already discussed. By analogy with these histamines, 4-methylimidazole 17a is often named distal [N(t)H] and 5-methylimidazole 17b, proximal [N(7t)H] (Scheme 9). 

M. Malfoy and J. A. Renaud J. Electroanal., Electrochemical investigations of amino acids at solid electrodes. Part II. Amino acids containing no sulfur atoms tryptophan, tyrosine, histidine and derivatives, Chem. Interfacial Electrochem, 114,213,1980. 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

Interactions of histidine and other imidazole derivatives with transition metal ions in chemical and biological systems. R. J. Sundberg and R. B. Martin, Chem. Rev., 1974, 74, 471-517 (517). 

Decarboxylation of histidine forms histamine, and several dipeptides are derived from histidine and P-alanine. 

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... 

As early as 1905 Abderhalden (Al) isolated from the hydrolyzate of the nondiffusible fraction of human urine four amino acids, i.e., leucine, alanine, glycine, and glutamic acid, and detected two others phenylalanine and aspartic acid. Some amino acids derived from this fraction have been quantitatively determined by Albanese et al. (A3) who found in the amount of the nondiffusible fraction corresponding to one liter of urine as much as 32.8 mg tryptophan, 18.0 mg phenylalanine, 16.2 mg methionine, 15.2 mg cystine, 13.1 mg arginine, 6.7 mg histidine, and 3.9 mg tyrosine. 

The most successful modifier is cinchonidine and its enantiomer cinchonine, but some work in expanding the repertoire of substrate/modifier/catalyst combinations has been reported (S)-(-)-l-(l-naphthyl)ethylamine or (//)-1 -(I -naphth T)eth Tamine for Pt/alumina [108,231], derivatives of cinchona alkaloid such as 10,11-dihydrocinchonidine [36,71], 2-phenyl-9-deoxy-10, 11-dihydrocinchonidine [55], and O-methyl-cinchonidine for Pt/alumina [133], ephedrine for Pd/alumina [107], (-)-dihydroapovincaminic acid ethyl ester (-)-DHVIN for Pd/TiOz [122], (-)-dihydrovinpocetine for Pt/alumina [42], chiral amines such as 1 -(1 -naphtln I)-2-(I -pyrro 1 idiny 1) ethanol, l-(9-anthracenyl)-2-(l-pyrrolidinyl)ethanol, l-(9-triptycenyl)-2-(l-pyrrol idi nyl)cthanol, (Z )-2-(l-pyrrolidinyl)-l-(l-naphthyl)ethanol for Pt/alumina [37,116], D- and L-histidine and methyl esters of d- and L-tryptophan for Pt/alumina [35], morphine alkaloids [113],... 

The number of known or presumed mononuclear, non-heme iron oxygenases and related enzymes continues to grow. This is due to intensive biochemical research and especially based on sequence data derived from genome research projects i.14). For several of these enzymes structural data are available by now from protein crystallography (12-14). In many of the iron oxygenases the iron is facially bound by two histidines and one carboxylate donor, either glutamic acid or aspartic acid. Thus, the term 2-His-l-carboxylate facial triad has been introduced by L. Que Jr. for this motif (19). 

Orioli, M., Aldini, G., Benfatto, M. C., Facini, R. M., and Carini, M. (2007). HNE Michael adducts to histidine and histidine-containing peptides as biomarkers of lipid-derived carbonyl stress in urines LC-MS/MS profiling in Zucker obese rats. Anal. Biochem. 79, 9174-9184. 

The occurrence of alanine in proteins was first shown by Schutzen-berger, who did not actually identify his product with the synthetical one Weyl in l88i obtained it as a decomposition product of silk and showed that his preparation was similar in properties to Strecker s synthetical alanine. He thus established it as a constituent of a protein molecule. The researches of Emil P ischer have shown that alanine is a constant constituent of all proteins. It is worthy of note that of the eighteen definitely determined units of a protein molecule, six of them, namely, isoleucine, phenylalanine, tyrosine, serine, histidine and tryptophane, are derivatives of a-aminopropionic acid. 

The unstable thiazolinones are converted into stable hydantoines in order to facilitate their identification. Conversion and identification are carried out outside the instrument after extraction of the thiazolinones with butylchlor-ide. The conversion reaction as well as the problems associated with identification of the PTH-amino acids were studied in detail by Edman and described explicitly in Needleman s book on Protein Sequence Determination Conversion is generally carried out in 1 N HCl at 80 °C within 10 min. The PTH-derivatives are extracted from the aqueous phase with ethyl acetate with the exception of PTH-arginine, PTH-histidine and PTH-cysteine which remain in the aqueous phase. 

Tomita M, Irie M, Ukita T. Sensitized photooxidation of histidine and its derivatives. Products and mechanism of the reaction. Biochemistry 1969 8(12) 5149—5160. 

---