Aims/introduction: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue.

Materials And Methods: The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 participants (men/women: 224/260) of the Tanno-Sobetsu Study.

Results: Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in men than in women. In 59 participants with hyperuricemia, 11 (men/women: 11/0) participants were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in participants without treatment. In all of the participants, hypoxanthine concentration in smokers was significantly higher than that in non-smokers. Stepwise and multivariate regression analyses showed that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity.

Conclusions: The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378426PMC
http://dx.doi.org/10.1111/jdi.13207DOI Listing

Publication Analysis

Top Keywords

hypoxanthine xanthine
24
plasma xor
20
xor activity
20
independent predictors
12
hypoxanthine
11
xanthine
11
differential regulation
8
regulation hypoxanthine
8
general population
8
xor
8

Similar Publications

: Current urate-lowering therapies may cause serious side effects in patients. Thus, alternative treatments are needed to regulate uric acid (UA) levels in patients with hyperuricemia associated with kidney injury, and natural antioxidant sources have demonstrated utility in this field. For the first time, our study evaluated the effects of an extract of insects on the levels of xanthine oxidase (XO) enzymes and synthetic free radicals in vitro and in vivo.

View Article and Find Full Text PDF

Background: Urate transporter 1 (URAT1) is a well-known therapeutic target for reducing urate levels in the treatment of hyperuricemia and gout. However, current pharmacological studies have failed to evaluate the efficacy of URAT1 inhibitors in non-primate animal models. We established a human URAT1 (hURAT1) transgenic knock-in (KI) mouse model to assess uricosuric agents' effectiveness and characterize URAT1-caused pathogenesis.

View Article and Find Full Text PDF

A patent review of xanthine oxidase inhibitors (2021-present).

Expert Opin Ther Pat

December 2024

Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.

Introduction: Xanthine oxidase (XO) catalyzes the oxidation of both hypoxanthine and xanthine in the last two steps of the purine metabolic pathway, serving as a rate-limiting enzyme for uric acid production as well as a key target for the treatment of gout and other hyperuricemia-related conditions.

Areas Covered: This paper reviews XO inhibitors in patents from 2021 to the present. We summarize in detail the structural classes and characteristics, in vitro and in vivo biological results, and structure‒activity relationships of synthetic inhibitors, as well as the sources, specific structures, research methods, and biological activities of XO inhibitors from natural products.

View Article and Find Full Text PDF

Serum metabolic profiles in quails: Effects of age, breed, and sex.

Poult Sci

January 2025

Jiangxi Provincial Key Laboratory of Poultry Genetic Improvement, Nanchang Normal University, Nanchang, Jiangxi 330032, China. Electronic address:

Over the past decade, metabolomic research in livestock and poultry has gained considerable momentum; however, quail metabolomics still lags behind that of livestock species such as chickens, pigs, and cattle. Quails are important models due to their low-cost protein sources-both eggs and meat-and practical benefits such as minimal space requirements, high egg production, disease resistance, and rapid reproduction. Therefore, it is necessary to systematically understand the effects of various factors on quail metabolism to provide a theoretical basis for accurate feeding and breeding practices.

View Article and Find Full Text PDF

Identification of new inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine Phosphoribosyltransferase (HG(X)PRT): An outlook towards the treatment of malaria.

Int J Biol Macromol

January 2025

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center of Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 22252, Saudi Arabia. Electronic address:

Article Synopsis
  • Plasmodium, the parasite causing malaria, relies on the purine salvage pathway for survival, making its enzymes, like HGXPRT, potential targets for new antimalarial drugs.
  • The study focused on inhibiting HGXPRT to disable the parasite's nucleotide synthesis, optimizing assays to evaluate over 200 compounds for their inhibitory effects.
  • Fourteen compounds were identified as effective inhibitors, with promising interactions at the enzyme's binding site, and they were shown to be non-toxic to human cells, setting the stage for further drug development.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!