Deoxycholate oxidation

Irradiation in air of the deoxycholic acid (DCA, 157) complex of indanone leads to oxidation of both the steroid and the guest, yielding 5- 3-hydroxy-DCA, 158, and optically active 3-hydroxyindanone (241). In the presence of air, irradiation of the DCA clathrates of isochromane, 159, and indene, 161, leads to reaction with oxidation of the host and of the allylic position of the guest to a keto group (e.g., 159 — 160 and 161 — 162).The detailed mechanisms of these oxidations remain to be elucidated. 

Micromolar quantities of RNS are generated primarily by nitric oxide synthase 2 (NOS2), an enzyme that is up-regulated during colon-cancer progression. As discussed below, deoxycholate (DOC), a hydrophobic secondary bile acid, activates the redox-sensitive transcription factor NF-kB, resulting in increased levels of NOS2 and enhanced S-nitrosylation of proteins. Additional sources of bile-acid-induced ROS and RNS are also likely. ... 

H. Bernstein, C. M. Payne, C. Bernstein, J. Schneider, S. E. Beard and C. L. Crowley, Activation of the promoters of genes associated with DNA damage, oxidative stress, ER stress and protein malfolding by the bile salt, deoxycholate, Toxicol. Lett., 1999, 108(1), 37. 

C. M. Payne, C. Weber, C. Crowley-Skillicorn, K. Dvorak, H. Bernstein, C. Bernstein, H. Holubec, B. Dvorakova and H. Garewal, Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB through multiple mechanisms in HCT-116 colon epithelial cells, Carcinogenesis, 2007, 28(1), 215. 

The oxidation of L-glycerol 3-phosphate to dihydroxyacetone phosphate is catalyzed by two different enzymes. One is the cytoplasmic NAD-linked a-glycerophosphate dehydrogenase, and the other is the mitochondrial enzyme, which appears to contain flavin and iron. The latter enzyme was first studied by Green in 1936 (223). It was shown to be associated with respiratory particles, and widely distributed in animal tissues. The highest concentration of the enzyme was found in the brain. Lardy and co-workers (234) studied the enzyme in deoxycholate-solubilized particles obtained from skeletal muscle, confirmed the finding... 

Bile-acid formation in rats involves hydroxylation to give 7a- and 6j8-hydroxy-derivatives. In many cases, no isotope effect was observed on hydroxylation of the appropriate labelled sterol. These examples involve cytochrome P-450 in the oxidation. However, oxidation of [7a- H,24- C]deoxycholic acid or tauro-deoxycholic acid to the corresponding cholic acid showed an isotope effect of 3.8 on examination of recovered starting material. 

The intestinal microflora of man and animals can biotransform bile acids into a number of different metabolites. Normal human feces may contain more than 20 different bile acids which have been formed from the primary bile acids, cholic acid and chenodeoxycholic acid [1-5], Known microbial biotransformations of these bile acids include the hydrolysis of bile acid conjugates yielding free bile acids, oxidation of hydroxyl groups at C-3, C-6, C-7 and C-12 and reduction of oxo groups to give epimeric hydroxy bile acids. In addition, certain members of the intestinal microflora la- and 7j8-dehydroxylate primary bile acids yielding deoxycholic acid and lithocholic acid (Fig. 1). Moreover, 3-sulfated bile acids are converted into a variety of different metabolites by the intestinal microflora [6,7]. 

Humans do not oxidize cholesterol for energy. Instead, cholesterol is converted to bile acids such as cholic acid and deoxycholic acid in liver tissue. Bile acids and salts are secreted into bile, which passes into the intestine and emulsifies fats for digestion. Although some bile acids may be reabsorbed in the intestine along with lipids, much cholesterol leaves the body in feces in the form of metabolites such as bile acids and salts. 

When denitrifying bacteria are grown anaerobically on nitrite, nitrogen gas is usually released. However, if cell-free extracts are incubated under anaerobic conditions with nitrite, nitrous oxide and nitric oxide are produced in addition to nitrogen. The reduction of nitrite to nitrogen requires the participation of both soluble and particulate components and NADH or respiratory intermediates such as succinate or lactate (Naik and Nicholas, 1966 Lam and Nicholas, 1969 Payne et al., 1971 Cox and Payne, 1973). When deoxycholate solubilized preparations are used, artificial electron carriers such as reduced viologen dyes or flavins must be used (Radcliffe and Nicholas, 1%8). 

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