Rhodoquinone (RQ) is an important cofactor used in the anaerobic energy metabolism of Rhodospirillum rubrum. RQ is structurally similar to ubiquinone (coenzyme Q or Q), a polyprenylated benzoquinone used in the aerobic respiratory chain. RQ is also found in several eukaryotic species that utilize a fumarate reductase pathway for anaerobic respiration, an important example being the parasitic helminths. RQ is not found in humans or other mammals, and therefore inhibition of its biosynthesis may provide a parasite-specific drug target. In this report, we describe several in vivo feeding experiments with R. rubrum used for the identification of RQ biosynthetic intermediates. Cultures of R. rubrum were grown in the presence of synthetic analogs of ubiquinone and the known Q biosynthetic precursors demethylubiquinone, demethoxyubiquinone, and demethyldemethoxyubiquinone, and assays were monitored for the formation of RQ 3 . Data from time course experiments and S-adenosyl-L-methionine-dependent O-methyltransferase inhibition studies are discussed. Based on the results presented, we have demonstrated that Q is a required intermediate for the biosynthesis of RQ in R. rubrum.Rhodospirillum rubrum is a well-characterized and metabolically diverse member of the family of purple nonsulfur bacteria (29, 61). R. rubrum is typically found in aquatic environments and can adapt to a variety of growth conditions by using photosynthesis, respiration, or fermentation pathways (28, 70). In the light, R. rubrum exhibits photoheterotrophic growth using organic substrates or photoautotrophic growth using CO 2 and H 2 (15, 70). In the dark, R. rubrum can utilize either aerobic respiration (70,73) or anaerobic respiration with a fumarate reduction pathway or with nonfermentable substrates in the presence of oxidants such as dimethyl sulfoxide (DMSO) or trimethylamine oxide (15,58,73). R. rubrum can also grow anaerobically in the dark by fermentation of sugars in the presence of bicarbonate (58). The focus of this work was the biosynthesis of quinones used by R. rubrum for aerobic and anaerobic respiration.Rhodoquinone (RQ; compound 1 in Fig. 1) is an aminoquinone structurally similar to ubiquinone (coenzyme Q or Q [compound 2]) (44); however, the two differ considerably in redox potential (that of RQ is Ϫ63 mV, and that of Q is ϩ100 mV) (2). Both RQ and Q have a fully substituted benzoquinone ring and a polyisoprenoid side chain that varies in length (depending on the species; see Fig. 1 for examples). The only difference between the structures is that RQ has an amino substituent (NH 2 ) instead of a methoxy substituent (OCH 3 ) on the quinone ring. While Q is a ubiquitous lipid component involved in aerobic respiratory electron transport (9, 36, 60), RQ functions in anaerobic respiration in R. rubrum (19) and in several other phototrophic purple bacteria (21,22,41) and is also present in a few aerobic chemotrophic bacteria, including Brachymonas denitrificans and Zoogloea ramigera (23). In these varied species of bacteria, RQ has been ...
Gastroesophageal reflux disease (GERD) has been hypothesized as a risk factor for development of laryngeal cancer. A case-control study was performed to assess the association of laryngeal neoplasia with GERD. Cases consisted of patients with a history of laryngeal cancer or carcinoma in situ. Controls were patients without neoplasia who matched cases 2:1 on age, sex, race, and smoking history. Univariate and multivariate analyses were performed to assess risk of laryngeal neoplasia and GERD. In total, 2094 patients were included. Cases had higher rates of GERD. Univariate analysis demonstrated a positive association between GERD and laryngeal neoplasia (odds ratio, 1.33; 95% CI, 1.07-1.64). Multivariate analysis controlling for alcohol use history also demonstrated a positive association between GERD and laryngeal neoplasia (adjusted odds ratio, 1.29; 95% CI, 1.04-1.59). These results suggest increased odds of laryngeal carcinoma and carcinoma in situ in patients with GERD when controlling for smoking and drinking history.
aerodigestive tract impairments. GERD and LPR are different pathophysiological conditions and involve different pH study findings. 2 Many patients with GERD have no LPR and vice versa. According to the ProGERD Study, Jaspersen et al 3 showed that laryngopharyngeal complaints were present among 32.8% of patients with GERD. In fact, patients with severe GERD may have a higher probability of having LPR, but most GERD patients have no LPR and, consequently, no gastric contents coming up into the upper aerodigestive tract mucosa. 4 The difference between GERD and LPR is important when the aim of the study is to investigate the potential impact of reflux on the development of neoplasia. Indeed, the diagnosis of LPR includes the objectification of laryngopharyngeal reflux episodes, meaning the reflux of gastric content into the upper aerodigestive tract. 2 With regard to basic science studies, 5 the carcinogenesis potential of reflux is probably due to irritation of gastric contents (ie, pepsin, bile salts) into the laryngeal and vocal fold mucosa, which may induce cell proliferation through modulation of signaling pathways. 5
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