Citrulline

M.p. 222 C. Soluble in water, insoluble in alcohol. Citrulline is an intermediate in the urea cycle in the excretion of excess nitrogen from the body. 

Three years later Robert F Furchgott discov ered that the relaxing of smooth muscles such as blood vessel walls was stimulated by an unknown substance produced in the lining of the blood vessels (the endothelium) He called this substance the endothelium-dependent relaxing factor or EDRF and in 1986 showed that EDRF was NO Louis J Ignarro reached the same conclusion at about the same time Further support was provided by Salvador Moncada who showed that endothelial cells did in deed produce NO and that the l arginine to l citrulline conversion was responsible... 

S-Citrulline (2>amino-5-ureidopentanoic acid) [372-75-8] M 175.2, m 222°, [o] +24.2° (in 5M HCl), pK 9.71. Likely impurities are arginine, and ornithine. Crystd from water by adding 5 volumes of EtOH. Also crystd from water by addn of MeOH. 

Likely impurities are citrulline, arginine and D-omithine. Crystd from water by adding 4 volumes of EtOH and dried in a vacuum desiccator over fused CaCl2. 

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. 

Antibodies to Cyclic-citrullinated Peptides (Anti-CCPs)... 

QH,4N402 74-79-3) see Arginine aspartate Arginine pidolate Cetrorelix l arginine monohydrochloride (QH15CIN4O2 1119-34-2) see Citrulline D-Arg(Tos)-Gly-OEt... 

Carbamoyl Phosphate Plus Ornithine Forms Citrulline... 

L-Ornithine transcarbamoylase catalyzes transfer of the carbamoyl group of carbamoyl phosphate to ornithine, forming citrulline and orthophosphate (reaction 2, Figure 29-9). While the reaction occurs in the mitochondrial matrix, both the formation of ornithine and the subsequent metabolism of citmlline take place in the cytosol. Entry of ornithine into mitochondria... 

Argininosuccinate synthase links aspartate and citrulline via the amino group of aspartate (reaction 3, Figure 29-9) and provides the second nitrogen of urea. The reaction requires ATP and involves intermediate formation of citrullyl-AMP. Subsequent displacement of AMP by aspartate then forms citrulline. 

All defects in urea synthesis result in ammonia intoxication. Intoxication is more severe when the metabolic block occurs at reactions 1 or 2 since some covalent linking of ammonia to carbon has already occurred if citrulline can be synthesized. Clinical symptoms common to all urea cycle disorders include vomiting, avoidance of high-protein foods, intermittent ataxia, irritability, lethargy, and mental retardation. The clinical features and treatment of all five disorders discussed below are similar. Significant improvement and minimization of brain damage accompany a low-protein diet ingested as frequent small meals to avoid sudden increases in blood ammonia levels. 

Arginine deiminase (ADI) pathway (Mercenier et al. 1980) arginine —> citrulline ornithine + carbamoyl phosphate... 

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