Citrulline methyl

The interaction with both synthetic and naturally occurring amino acids has been studied extensively glycine (138, 173, 219-221), a-(173, 219) and /3-alanine (138, 220), sarcosine (219), serine (222), aspartic acid (138, 173, 222-226), asparagine (222), threonine (222), proline (219), hydroxyproline (219), glutamic acid (138, 222-225), glutamine (222), valine (219, 227), norvaline (219), methionine (222, 226), histidine (228, 229), isoleucine (219), leucine (219, 230), norleu-cine (219), lysine (222), arginine (222), histidine methyl ester (228), phenylalanine (138, 222), tyrosine (222), 2-amino-3-(3,4-dihydroxy-phenyl jpropanoic acid (DOPA) (222), tryptophan (222), aminoiso-butyric acid (219), 2-aminobutyric acid (219,231), citrulline (222), and ornithine (222). 

Figure 1.1 PTMs found on the first 30 residues of the human histone proteins. Only acetylation, methylation, deimination (formation of citrulline) and phosphorylation are shown.

Thompson, P.R. and Fast, W. (2006) Histone citrullination by protein arginine deiminase is arginine methylation a green light or a roadblock ACS Chemical Biology, 1, 433-441. 

Raijmakers R, et al. Methylation of arginine residues interferes with citrullination by peptidylarginine deiminases in vitro. J. Mol. 

Cedrangolo et al (C5) and De Lorenzo (Dl) also postulated an alternative pathway on the basis of their experimental results on rats. The animals were injected with a-methyl aspartate, a specific inhibitor for argininosuccinate synthetase. No effect on urea excretion was observed, but there was complete inhibition of urea synthesis from citrulline in liver homogenates prepared from injected animals, as well as increased susceptibility to ammonia intoxication. However, this inhibition was not confirmed by Crokaert and Baroen (C15, C16, C17), although they did confirm the lack of any effect on urea excretion. The experimental basis for this suggestion is therefore in doubt. 

DDAH catalyzes the hydrolysis of A -methyl-L-arginine (12) and asymmetric A -dimethyl-L-argtnine (13) to yield L-citrulline (1) and the corresponding alkylamine (Figure 9)." " In vertebrates, two tissue-specific... 

Arginine methylation and citrullination may be antagonistic posttranslational modifications that compete with one another. Methylation of arginine residues found in PAD substrates can block their citrullination. In vitro studies found that methylated arginines are only poor substrates of PAD and are unlikely to be significantly modified. However, in vivo experiments indicate that PAD4 can hydrolyze monomethylated (but not dimethylated) arginine. The interplay of these two posttranslational modifications is an active area of study. 

Amino-acid analogs and uncommon L-amino acids W-acetyl-aspartate, W-acetyl-serine, oi-amino-n-butyrate, 3-aminoisobutyrate, aspartate ethyl or methyl ester, citrulline, cysteate, fumarate, glutathione, homoserine, erythro- and threo-p-hydroxyaspartate, isoasparagine, isoserine, malate, a- and p-methylaspartate, methylserine, phenol, serine amide, serine methyl ester, succinate [498, 747]... 

CgH,7N304, Mr 219.24, cryst., mp. 184-188 °C (decomp.), [a] 3 +25.5° (HjO), soluble in water and methanol. C. occurs together with lyophyllin and AT-hydroxy-A,Al-dimethylurea in Lyophyllum connatum (Agaricales). The biosynthesis starts from citrulline by methylation and subsequent A-hydroxylation. C. is the biosynthetic precursor of N -hydroxy-N,N-dimethylurea (C3H8N2O2, Mr 104.11, mp. 107-109°C) which, together with C., is responsible for the blue color reaction of the fruit bodies of L. connatum with iron(lll) chloride. 

Biosynthetic studies have established that D-glycosamine is incorporated into streptozotocin, and L-citrulline and methionine furnish the amide side-chain and A -methyl group, respectively, but the source of the nitroso-group was not established. ... 

Fig. 2. The elution pattern of a standard mixture of OPA-derivatized primary amines, separated on a 5 (Jim Nucleosil C-18 column (200 X 4.6 mm id). The flow-rate was 1 mL/min employing the indicated gradient of metlianol and Na phosphate buffer (50 mA4, pH 5.25). Each peak represents 39 pmol except for those indicated below. 1, glutathione 2, cysteic acid 3, O-phosphoserine (19.5 pmol) 4, cysteine sulfinic acid 5, aspartic acid 6, asparagine (19.5 pmol) 7, glutamic acid 8, histidine 9, serine 10, glutamine 11, 3-methyl-histidine 12, a-aminoadipic acid (9.8 pmol) 13, citrulline (9.8 pmol) 14, carnosine 15, threonine,glycine 16, O-phosphoethanolamine 17, taurine (19.5 pmol) 18, p-alanine (19.5 pmol) 19, tyrosine 20, alanine 21, a-aminoisobutyric acid 22, aminoisobutyric acid 23, y-amino-ii-butyric acid 24, p-amino-u-butyric acid 25, a-amino-butyric acid 26, histamine 27, cystathione (19.5 pmol) 28, methionine 29, valine 30, phenylalanine 31, isoleucine 32, leucine 33, 5-hydroxytryptamine (5-H i ) 34, lysine. The chromatographic system consisted of a Varian LC 5000 chromatograph and a Schoeffel FS 970 fluorimeter.

In addition to more or less complete amino acid separations, suitable chromatographic systems for the rapid determination of selected amino acids [4-amino-butyric acid (GABA) [336], histidine and 3-methylhisti-dine [367] or a group of selected amino acids, such as those involved in the urea cycle (arginine, citrulline, ornithine, agmatine) [368], have been reported. Precolumn derivative formation with OPA/R-SH reagents is also suited to the automated establishment of peptide maps [369]. A number of authors have published methods for the sensitive determination of aminoglycoside antibiotics [365,370—373]. The method has also found application for the determination of histamine and its methylation products [374—376], catecholamines and serotonin [377—379] and polyamines [380]. 

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