Citrulline solubility

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. 

Cohen and Grisolia then concentrated on the first step in the reaction, obtaining citrulline from ornithine. The reaction appeared to depend on oxygen, a requirement traced to the need for high concentrations of ATP. Physiologically the formation of urea occurs at very low levels of ammonia, which is extremely toxic as it is also lipid soluble and enters cells very easily. Cells are not very effectively buffered against OH. ... 

There are cytosolic and membrane-bound isoforms of NO synthase. Certain soluble and particulate isoforms are constitutive and other soluble isoforms are inducible. The constitutive enzyme is, by definition, present in the catalytically active form and needs only to be stimulated by an appropriate chemical species, following which there is immediate formation of NO plus L-citrulline. This form of NO synthase requires calcium, and for the most part calmodulin, for stimulation of enzymatic activity. It is likely that an increase in intracellular free calcium in the presence of calmodulin is the signal for stimulation of NO synthase, and therefore, the production of NO. This view is consistent with the general understanding that, in vascular tissue, all endothelium-dependent vaso-... 

This observation led to the finding that a soluble enzyme from rat forebrain catalyzes the NADPH-dependent formation of NO and L-citrulline from L-ar-ginine by calcium-dependent mechanisms (Knowles et al., 1989). A subsequent study revealed that glutamate and NMDA stimulate NO and L-citrulline formation in rat cerebellar slices and that this is associated with a concomitant stimulation of cyclic GMP formation (Bredt and Snyder, 1989), thus establishing a link between NMDA-receptor activation and cyclic GMP formation (Fig. 4). These investigators went on to purify and characterize NO synthase from cerebellum (Bredt and Snyder, 1990 Bredt et al., 1991) and to show the localization of NO synthase in the brain to discrete neuronal populations (Bredt et al., 1990). 

A number of amino acid transport disorders may be associated with one or several of the systems described in Table 20.4. These are characterized by the excretion of amino acids in the urine but no increase in amino acid levels in the bloodstream. They are usually of hereditary origin. The most common disorder is cystinuria, characterized by the excretion of cystine. Because cystine is only slightly water soluble, cystinuria is often accompanied by the deposition of cystine-containing stones in the genitourinary tract. Cystinuria is apparently caused by a defect in the cationic amino acid transport system. Another disease that affects this system is lysinuric protein intolerance, which is associated with a failure to transport lysine, ornithine, arginine, and citrulline across membranes. Citrulline and ornithine are urea cycle intermediates (see later), and a disruption of their interorgan traffic results in hyperammonemia. 

Nitric oxide is synthesized from the amino acid arginine in a reaction catalysed by NOS I-arginine + 02 + NADPH — citrulline + NADP+ + NO (thiol, tetrahydrobiopterin, FMN and FAD being requisite cofactors in this process). NO subsequently acts by activating soluble GC, thereby successively causing elevation of cGMP and PKG activation. NO can also act by activating Ca2 1 -dependent K+ channels. 

Nitric oxide is a molecule with pleiotropic effects on the cardiovascular system. Figure 15. Nitric oxide (NO) is produced when NO synthase (NOS) converts L-ar-ginine to citrulline. The major target of NO in the cardiovascular system is the NO sensitive soluble guanyl cyclase that converts guanosine triphosphate (GTP) to c-GMP. 

NO has a short half-life (2-30 s) and therefore the direct measurement of NO production is impractical. In aqueous solutions, however, it rapidly reacts with oxygen to form the stable water-soluble metabolites nitrite and nitrate (Figure 1). The concentration of these ions, which can be measured via a variety of methods, is used as a measure of the tissue content of NO and/or the synthesis of NO by cultured cells (Hevel and Marietta, 1994 Archer, 1993). An alternative method used to quantify NOS activity is to directly measure the catalytic activity of a cell or tissue extract (i.e., the conversion of radioactive arginine to citrulline Hevel and Marietta, 1994 Archer, 1993). While both methods are sensitive measurements of the overall capacity of a cell or tissue extract to synthesize NO, neither one provides a true kinetic... 

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. 

After its activation, eNOS converts its substrate l arginine into NO and l citrulline. NO can diffuse freely in the vascular wall and reach the smooth muscle cells where it activates soluble guanylyl cyclase, an enzyme-transforming guanosine-5 -triphosphate (GTP) into guanosine 3, 5 -cyclic monophosphate (cGMP). 

Citrulline Synthesis. The first syntheses of citrulline and arginine by the addition of NHa and CO2 to ornithine were achieved in the laboratory of Cohen, where soluble enzymes of liver supplemented with cell particles were found to carry out these syntheses. The soluble extract was found to contain the several activities involved in the reactions of the urea cycle, while the particles were found to function solely as a source of ATP. The synthesis of citrulline was found to require ornithine, CO2, NH3, and... 

Soluble Enzymes. Very many enzymes appear to be present in solution in cytoplasm. The glycolytic enzymes are all found in the soluble fraction of homogenates. The report that glycolysis is stimulated by the addition of other components cannot be evaluated now it may be that glycolysis does involve additional elements of the cell, or it may be that some enzymes are adsorbed to particles. The enzymes of many ATP-requiring reactions are found in the soluble fraction. Early work on many of these systems, such as those that form citrulline and arginine, showed a requirement for mitochondria, but this requirement was eventually found to be related only to the ability of mitochondria to form ATP. 

Oenersl Properties of the Amino Acids.— All the natural acids are colourless crystalline solids. All, except cystine, leucine, and tyrosine, are readily soluble in water and all, except proline and hydroxyproline, are sparingly soluble in alcohol. AU are optically active, except glycine, the a-carbon of which is not asymmetric. The dextro acids are alanine, valine, iso-leucine, glutamic acid, hydroxyglutamic acid, aspartic acid, arginine, citrulline, and lysine. The others are IsBvo-rotatory. 

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