Xanthine

About: Xanthine is a research topic. Over the lifetime, 4046 publications have been published within this topic receiving 129820 citations. The topic is also known as: Xanthine.

A Leishmania major nucleobase transporter responsible for allopurinol uptake is a functional homolog of the Trypanosoma brucei H2 transporter.

Abstract: Nucleobase transporters play an important role in the physiology of protozoan parasites, because these organisms are purine auxotrophs and rely entirely on salvage of these vital compounds. Purine transporters have also been shown to mediate the uptake of important antiparasitic drugs. In the current study, we investigated the uptake of [3H]adenine, [3H]hypoxanthine, and [3H]allopurinol, an antileishmanial hypoxanthine analog, by Leishmania major. These compounds were all taken up by a single high-affinity transporter, LmNBT1, withKm values of 4.6 ± 0.9, 0.71 ± 0.07, and 54 ± 3 μM, respectively. Guanine and xanthine fully inhibited [3H]adenine transport, withKi values of 2.8 ± 0.7 and 23 ± 8 μM. Using purine analogs, an inhibitor profile for LmNBT1 was obtained, which allowed the construction of a quantitative model for the interactions between the transporter binding site and the permeant. The model predicts that hypoxanthine was bound through hydrogen bonds to N(1)H, N3, N7, and N(9)H of the purine ring, with a total Gibbs free energy of −39.5 kJ/mol. The interactions with adenine were similar, except for a weak hydrogen bond to N1 (unprotonated in adenine). The predicted mode of substrate binding for LmNBT1 was almost identical to that for the Trypanosoma brucei H2 (TbH2) transporter. It is proposed that the architecture of their respective binding sites is very similar and that LmNBT1 can be named a functional homolog of TbH2.

Antioxidant defences in rat, pig, guinea pig, and human hearts: comparison with xanthine oxidoreductase activity

Abstract: Objective: Cardiac injury, related to ischaemia and reperfusion, may be caused by the action of oxygen free radicals. Xanthine oxidoreductase activity may be an important free radical source. During cardiac ischaemia, the native dehydrogenase form may be converted to the oxidase form, which uses molecular oxygen to form superoxide radicals. Superoxide dismutase converts the radicals to H2O2, which is detoxified by catalase and glutathione peroxidase. In view of the large differences in xanthine oxidoreductase in various species, the activity of these antioxidant enzymes was investigated. Methods: Normal rodent and porcine as well as explanted human hearts were perfused according to Langendorff. After a 30 minute stabilisation period, hypoxanthine was added to the perfusion buffer to estimate xanthine oxidoreductase. Hearts or biopsies were freeze clamped after 90 minutes. Effluent xanthine and urate were assayed with high performance liquid chromatography; tissue reduced glutathione content and the activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were determined spectrophotometrically. Apparent xanthine oxidoreductase was calculated as xanthine + 2 × urate production. Results: Xanthine oxidoreductase was (mU·g-1 protein, mean(SEM), n = 5-7): rat, 470(40); Guinea pig, 270(41); pig < 1.5; and human, 5.4(1.0). Superoxide dismutase activities were (U·g-1 protein): rat, 13 370(1030); Guinea pig, 10 100(1110); pig, 12 800(450); and human, 7400(450). Catalase activity (k ≤ 10·g-1 protein) was low in all species studied. Glutathione peroxidase activity was 93(7) U·g-1 protein in rat heart, and 10 × lower in the other species. Glutathione reductase activity was (U·g-1 protein): rat, 15.0(1.6); Guinea pig. 10.4(1.3); pig, 16.0(1.5); and human, 26.6(2.0). Tissue reduced glutathione concentrations were (μmol·g-1 protein): rat, 13.5(0.8); Guinea pig, 18.5(0.9); pig, 11.1(2.9); and human 17.2(1.7). Conclusions: Considerable species differences in xanthine oxidoreductase activity exist, contrasting with the smaller variations in antioxidant enzyme activities. In the species examined catalase activities were very low. Rat hearts are far better protected against H2O2 than the other three species. Xanthine oxidoreductase induced free-radical damage probably plays a minor role in pig and human hearts. Human myocardium seems less protected against superoxide radicals.Cardiovascular Research 1993;27:2052-2057.

Xanthine dehydrogenase: An old enzyme with new knowledge and prospects.

Abstract: Xanthine dehydrogenase (EC 1.17.1.4, XDH) is a typical and complex molybdenum-containing flavoprotein which has been extensively studied for over 110 years. This enzyme catalyzes the oxidation of purines, pterin and aldehydes with NAD+ or NADP+ as electron acceptor, and sometimes can be transformed to xanthine oxidase (EC 1.17.3.2, XOD) capable of utilizing oxygen as the electron acceptor. XDHs are widely distributed in all eukarya, bacteria and archaea domains, and are proposed to play significant roles in various cellular processes, including purine catabolism and production of reactive oxygen species (ROS) and nitric oxide (NO) in both physiological and pathological contexts. The recent applications of XDHs include clinical detections of xanthine and hypoxanthine content in body fluidics, and other diagnostic biomarkers like inorganic phosphorus, 5'-nucleotidase and adenosine deaminase. XDHs can also find applications in environmental degradation of pollutants like aldehydes and industrial application in nucleoside drugs like ribavirin. In this commentary, we would outline the latest knowledge on occurrence, structure, biosynthesis, and recent advances of production and applications of XDH, and highlighted the need to develop XDHs with improved performances by gene prospecting and protein engineering, and protocols for efficient production of active XDHs in response to the increasing demands.