Association of plasma xanthine oxidoreductase activity with vascular endothelial function independent of serum uric acid level: MedCity21 health examination registry

Kurajoh, Masafumi; Fukumoto, Shinya; Akari, Seigo; Murase, Takayo; Nakamura, Takashi; Ihara, Yasutaka; Imai, Takumi; Nagata, Yuki; Morioka, Tomoaki; Mori, Katsuhito; Imanishi, Yasuo; Watanabe, Toshio; Emoto, Masanori

doi:10.1016/j.ijcha.2023.101264

Cited by 1 publication

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“…The XO form produces superoxide ion (O2 •− ) and hydrogen peroxide (H 2 O 2 ) by monovalent and divalent electron transfer to O 2 , respectively, whereas the XDH form produces these ROSs at the FAD site by acting as a nicotinamide adenine dinucleotide hydrate (NADH) oxidase [7]. Plasma XOR activity has been reported to affect blood pressure [41], glycemic control [42], renal function [43], coronary artery spasm [44], vascular endothelial function [45], and carotid atherosclerosis [46], suggesting that ROS production by XOR is involved in these pathologies.…”

Section: Production Of Uric Acid and Dysuricemiamentioning

confidence: 99%

Dysuricemia

Nakayama,

Kurajoh,

Toyoda

et al. 2023

Biomedicines

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Gout results from elevated serum urate (SU) levels, or hyperuricemia, and is a globally widespread and increasingly burdensome disease. Recent studies have illuminated the pathophysiology of gout/hyperuricemia and its epidemiology, diagnosis, treatment, and complications. The genetic involvement of urate transporters and enzymes is also proven. URAT1, a molecular therapeutic target for gout/hyperuricemia, was initially derived from research into hereditary renal hypouricemia (RHUC). RHUC is often accompanied by complications such as exercise-induced acute kidney injury, which indicates the key physiological role of uric acid. Several studies have also revealed its physiological role as both an anti-oxidant and a pro-oxidant, acting as both a scavenger and a generator of reactive oxygen species (ROSs). These discoveries have prompted research interest in SU and xanthine oxidoreductase (XOR), an enzyme that produces both urate and ROSs, as status or progression biomarkers of chronic kidney disease and cardiovascular disease. The notion of “the lower, the better” is therefore incorrect; a better understanding of uric acid handling and metabolism/transport comes from an awareness that excessively high and low levels both cause problems. We summarize here the current body of evidence, demonstrate that uric acid is much more than a metabolic waste product, and finally propose the novel disease concept of “dysuricemia” on the path toward “normouricemia”, or optimal SU level, to take advantage of the dual roles of uric acid. Our proposal should help to interpret the spectrum from hypouricemia to hyperuricemia/gout as a single disease category.

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