Lysine, Ornithine, and Arginine

Little work has been done in the field of fluorinated lysines 5-fluorolysine has been prepared by fluorination of lysine with CF3OF/HF under UV irradiation, while preparation of 5,5-difluorolysine has been described by treatment of a suitable carbonyl precursor by SF4.  

In contrast, the 4-mono- and 4,4-difluoro analogues of ornithine have been the focus of many investigations. They are accessible starting from the corresponding fluoroglutamic derivatives.  

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Cystinuria is an autosomal recessive condition in which there is excessive urinary excretion of cystine because of a defect in proximal renal tubular reabsorption. In the most common form of the disease there is also excess excretion of the dibasic amino acids (lysine, ornithine, and arginine). These share the same renal tubular transporter although their presence in excess in urine appears benign. More rarely, isolated cystinuria is seen. The reader should note that cystinuria should not be confused with cystinosis, which is a condition associated with intracellular accumulation of cystine but not excess urinary excretion of cystine. 

Cystinuria is a disorder of renal and gastrointestinal tract amino acid transport that also affects lysine, ornithine, and arginine. The four amino acids share a common transport mechanism (discussed above). Clinically, it presents as urinary stone disease because of the insolubility of cystine. In cystinosis, cystine crystals are deposited in tissues because of a transport defect in ATP-dependent cystine efflux from lysosomes (discussed above). 

Cystinuria is a hereditary disease characterized by the excessive excretion of cystine, lysine, ornithine, and arginine in the urine, probably resulting from a deficiency in the renal tubular transport mechanism. Sir Archibald E. Garrod postulated that cystinuria resulted from a metabolic block involving the oxidation of cystine to sulfate. Later investigations of the pathogenesis of cystinuria demonstrated that the hereditary deficiency does not involve a metabolic block. If a metabolic impairment existed, cystine would be expected to accumulate in the plasma of cystinurics, but plasma levels of cystine are normal or low in cys-... 

However, although cystine clearance in some cystinurics equals that of inulin, clearance of lysine, ornithine, and arginine is markedly below that of inulin. These discrepancies between the reabsorption of cystine and that of the dibasic monocarboxylic acid are explained by the fact that the kidney possesses only one transport system for cystine, but it possesses two for lysine [171]. 

For identical but symmetrical reasons as those involved for the titrations of aspartic and glutamic acids, the titrations of lysine, ornithine, and arginine, which are a-amino acids bringing a supplementary amine function, can be performed with a... 

Electrolytic desalting converts some of the arginine to ornithine and causes a loss of between 10 and 30% of histidine, lysine, methionine, proline, and tyrosine (S50). Losses of certain amino acids also occur with the ion-exchange desalting procedure (C12). These include threonine, proline, methionine, leucine, isoleucine, ornithine, and arginine, and losses of between 7 and 37% occur for these amino acids when present in a synthetic mixture. 

Two major chemical modifications of proteins that occur during alkaline treatment are crosslinking and racemlzation. Lysine, ornithine (via arginine), cystine and 0-substituted serine can participate in base-catalyzed reactions forming the crossllnked amino acids lysinoalanine, ornithinoalanine and lanthionine Under the same conditions, inversion can occur when the or hydrogen of an amino acid residue is abstracted by the base, resulting in a planar, optically inactive carbanion ( ), as illustrated in Figure 1. The carbanion may be reprotonated from either face of the plane, which causes inversion when this occurs from the opposite face. 

Nicotine and anabasine are considered to be alkaloids derived firom nicotinic acid (pyridine-3-carboxylic acid).These alkaloids can be also classified as derived from ornithine and lysine, respectively. Therefore, these alkaloids are described in Chapter 10.1 (as alkaloids derived from nicotinic acid), in Chapter 3.1 (alkaloids derived from ornithine and arginine), and in Chapter 4.3 (alkaloids derived from lysine). However, such exceptions are relatively rare if the classification of alkaloids is conducted based on their biosynthetic origin. 

X 10 cm/min results. On the basis of this value, a mean transfer rate of 800 mg per 24 hours may be calculated for these amino acids we measured (glycine, aspartic acid, threonine, serine, glutamic acid, proline, valine, cystine, methionine, isoleucine, leucine, tyrosine, phenylalanine, ornithine, lysine, histidine and arginine). If and to what extent amino acids are absorbed by the... 

Major interfering substances found in the crude toxin preparation are citrulline, ethanolamine, ornithine, lysine and arginine. 

Cystinuria is a disorder of the proximal tubule s reabsorption of filtered cystine and dibasic amino acids (lysine, ornithine, arginine). 

Table 9.4. In the regions of overlapping solutes, glycine, and lysine have low relative weight responses. In addition, methionine, ornithine, histidine, arginine, tryptophan, and cysteine have significantly low responses.

Enantiomerically pure tripeptide aldehydes are typically synthesized by azide or mixed anhydride coupling of dipeptides to a-amino aldehydes or their semicarbazone derivatives. For example, Ac-Leu-Leu-Phe-H was synthesized by the azide coupling of Ac-Leu-Leu-OH with Phe-H semicarbazone, prepared by catalytic hydrogenation of Z-Phe-H semicarbazone. The tripeptide semicarbazone was deprotected with 37% HCHO/HC1 solution (Table 2)J5 C-terminal argininal, ornithinal, and lysinal peptides such as Z-Leu-Leu-Orn(Boc)-H and Z-Leu-Leu-Lys(Boc)-H were prepared by mixed anhydride coupling of Z-Leu-Leu-OH with Orn(Boc)-H semicarbazone or Lys(Boc)-H semicarbazone. 3 Z-Leu-Leu-Arg(N02)-H was prepared by mixed anhydride coupling of Z-Leu-Leu-OH with Arg(N02)-H semicarbazone trifluoroacetate, prepared from the reaction of TFA and Boc-Arg(N02)-H semicarbazone (Table 2) J31... 

Figure 8.1. Chromatograms produced on a 100 mm column of an amino acid analyser with 0.3 N sodium citrate solution (pH 7.00) as eluting agent (a) standard solution containing 1 unol/ml of each amino acid (b) 30 g of cabbage extract purified with Dowex 50-X8 in the ammonium form (0.97 mg of S-methylmethionine) and (c) the same sample as for (b) but after treatment at pH 10.0 for 30 minutes at 120 C. MMS S-methylmethionine, fils histidine, lys lysine, orn ornithine, arg arginine. From [12]...

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. 

The majority of alkaloids have been found to be derived from amino acids, such as tyrosine, phenylalanine, anthranilic acid, tryptophan/tryptamine, ornithine/arginine, lysine, histidine and nicotinic acid (Fig. 2.1). However, alkaloids maybe derived from other precursors such as purines in case of caffeine, terpenoids, which become aminated after the main skeleton has been synthesized i.e. aconitine or the steroidal alkaloids, are found in the Solanaceae and Liliaceae. Alkaloids may also be formed from acetate-derived polyketides, where the amino nitrogen is introduced as in the hemlock alkaloid, coniine. 

A-10. Many other nitrogenous compounds are formed in the intestine as a result of intestinal bacterial activity. Some have powerful pharmacological (vasopressor) effects. Intestinal bacteria convert lysine, arginine, tyrosine, ornithine and histidine to their vasopressor amines such as cadaverene, agmatine, tyramine, putrescine and histamine respectively. 

Since one of the most important, if not the most important, result of a defect of the biosynthesis of urea is an increased level of blood ammonia, it is essential to consider other conditions that might affect indirectly the urea cycle or in some other way raise the blood ammonia. For example, it has been suggested that since lysine can act as a competitive inhibitor of the conversion of arginine to ornithine and urea, an increased level of plasma lysine may therefore inhibit the urea cycle (B12). 

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