Ornithine conjugates

In many studies it is not necessary to isolate conjugated bile acid. It is simpler to work with free bile acids and a hydrolysis can be made at different stages of the work-up procedure. One should realize, however, that the nature of conjugated bile acids is not known in all details ornithine-conjugated bile acids have been described (57), esterified bile acids occur in feces (19), and sulfates were recently found in bile (47).Information about these compounds is lost upon hydrolysis. 

The pKa values of the recently discovered ornithine conjugates of bile acids and of the sulfate esters of glyco- and taurolithocholates have not yet been determined. 

Nicotinic Add Metabolism. The sequence of reactions leading to the formation of pyridine compounds is of particular interest as a source of nicotinic acid. Nutritional, isotopic, and genetic experiments have all shown that tryptophan and its metabolic derivatives including 3-hydroxy-anthranilic acid are precursors of nicotinic acid in animals and in Neuro-spora. The terminal steps in this sequence are not known. Under certain physiological conditions an increase in picolinic carboxylase appears to reduce nicotinic acid synthesis. This implies a common pathway as far as the oxidation of 3-hydroxyanthranilic acid. Whether quinolinic acid is a precursor of nicotinic acid is still uncertain. The enzyme that forms the amide of nicotinic acid also has not been isolated. Subsequent reactions of nicotinamide include the formation of the riboside with nucleoside phosphorylase and methylation by nicotinamide methyl-kinase. In animals W-methylnicotinamide is oxidized to the corresponding 6-pyridone by a liver flavoprotein. Nicotinic acid also forms glycine and ornithine conjugates. Both aerobic and anaerobic bacteria have been found to oxidize nicotinic acid in the 6-position. ... 

Ornithine decarboxylase is a pyridoxal dependent enzyme. In its catalytic cycle, it normally converts ornithine (7) to putrisine by decarboxylation. If it starts the process with eflornithine instead, the key imine anion (11) produced by decarboxylation can either alkylate the enzyme directly by displacement of either fluorine atom or it can eject a fluorine atom to produce viny-logue 12 which can alkylate the enzyme by conjugate addidon. In either case, 13 results in which the active site of the enzyme is alkylated and unable to continue processing substrate. The net result is a downturn in the synthesis of cellular polyamine production and a decrease in growth rate. Eflornithine is described as being useful in the treatment of benign prostatic hyperplasia, as an antiprotozoal or an antineoplastic substance [3,4]. 

The major substrates for amino acid conjugation are benzoic acid and related aromatic carboxylic acids such as phenylacetic acid, phenoxyacetic acid, cinnamic acid, etc. (21). In humans, the major amino acid utilized in the conjugation is glycine however, glutamine and taurine can also be cofactors. In birds, the major amino acid utilized is ornithine. 

Similiar to albomycin and ferrichromes, the linear tripeptide of A -hydroxy-A -acetyl-ornithine can be used as the simplest chiral template for artificial siderophores. It can be used alone as a tripeptide like for 80, can be conjugated to a hydrophobic fatty acid 81132 pj. p j.j longer peptide 82, 83, and 85. ... 

A number of amino acids can be used for conjugation of aromatic acids but the most common is glycine. Others utilized are taurine, glutamine, ornithine, for example. However, the one used may depend on the species of animal. 

Amino Acid Conjugation. In the second type of acylation reaction, exogenous carboxylic acids are activated to form S-CoA derivative in a reaction involving ATP and CoA. These CoA derivatives then acylate the amino group of a variety of amino acids. Glycine and glutamate appear to be the most common acceptor of amino acids in mammals in other organisms, other amino acids are involved. These include ornithine in reptiles and birds and taurine in fish. 

Use of the preformed Z-silyl enol ether 18 results in quite substantial anti/syn selectivity (19 20 up to 20 1), with enantiomeric purity of the anti adducts reaching 99%. The chiral PT-catalyst 12 (Schemes 4.6 and 4.7) proved just as efficient in the conjugate addition of the N-benzhydrylidene glycine tert-butyl ester (22, Scheme 4.8) to acrylonitrile, affording the Michael adduct 23 in 85% yield and 91% ee [10]. This primary product was converted in three steps to L-ornithine [10]. The O-allylated cinchonidine derivative 21 was used in the conjugate addition of 22 to methyl acrylate, ethyl vinyl ketone, and cydohexenone (Scheme 4.8) [12]. The Michael-adducts 24-26 were obtained with high enantiomeric excess and, for cydohexenone as acceptor, with a remarkable (25 1) ratio of diastereomers (26, Scheme 4.8). In the last examples solid (base)-liquid (reactants) phase-transfer was applied. 

The domestic fowl has an unusual mechanism for handling benzoic acid. This acid is conjugated with ornithine, instead of glycine, and ornithuric acids are excreted after administration of many aromatic acids. Until recently, it was not known whether or not the fowl could synthesize conjugates of glucuronic acid, but this information has now been supplied by Sperber.108 He has shown that, in the hen, intramuscular injection of... 

The main amino acids used to form the conjugates are glycine, glutamine, ornithine (birds), alanine (hamsters and mice), arginine and taurine. 

Amino acid conjugation has been reported to occur with glycine, glutamine, arginine, and taurine in mammals and certain primates. In other organisms, different amino acid acceptors are utilized in peptide conjugation. Ornithine is utilized by... 

Several other amino acids arc involved in the conjugation ofcarbo.xylic acids, but these reactions occur only occasionally and appear to be highly substrate and species depen-denl. " Ornithine (in birds), aspartic acid and serine (in rals), alanine (in mouse and hamster), taurine iH NCH CH2SO]H) (in mammals and pigeon.s), and histidine (in African bats) are among these amino acids. ... 

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