Physiological functions and pathogenic potential of uric acid: A review (original) (raw)
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Towards the physiological function of uric acid
Free Radical Biology and Medicine, 1993
Uric acid, or more correctly (at physiological pH values), its monoanion urate, is traditionally considered to be a metabolically inert end-product of purine metabolism in man, without any physiological value. However, this ubiquitous compound has proven to be a selective antioxidant, capable especially of reaction with hydroxyl radicals and hypochlorous acid, itself being converted to innocuous products (allantoin, allantoate, glyoxylate, urea, oxalate). There is now evidence for such processes not only in vitro and in isolated organs, but also in the human lung in vivo. Urate may also serve as an oxidisable cosubstrate for the enzyme cyclooxygenase. As shown for the coronary system, a major site of production of urate is the microvascular endothelium, and there is generally a net release ofurate from the human myocardium in vivo. In isolated organ preparations, urate protects against reperfusion damage induced by activated granulocytes, cells known to produce a variety of radicals and oxidants. Intriguingly, urate prevents oxidative inactivation of endothelial enzymes (cyclooxygenase, angiotensin converting enzyme) and preserves the ability of the endothelium to mediate vascular dilatation in the face of oxidative stress, suggesting a particular relationship between the site of urate formation and the need for a biologically potent radical scavenger and antioxidant.
Regulation of uric acid metabolism and excretion
International Journal of Cardiology, 2016
Purines perform many important functions in the cell, being the formation of the monomeric precursors of nucleic acids DNA and RNA the most relevant one. Purines which also contribute to modulate energy metabolism and signal transduction, are structural components of some coenzymes and have been shown to play important roles in the physiology of platelets, muscles and neurotransmission. All cells require a balanced quantity of purines for growth, proliferation and survival. Under physiological conditions the enzymes involved in the purine metabolism maintain in the cell a balanced ratio between their synthesis and degradation. In humans the final compound of purines catabolism is uric acid. All other mammals possess the enzyme uricase that converts uric acid to allantoin that is easily eliminated through urine. Overproduction of uric acid, generated from the metabolism of purines, has been proven to play emerging roles in human disease. In fact the increase of serum uric acid is inversely associated with disease severity and especially with cardiovascular disease states. This review describes the enzymatic pathways involved in the degradation of purines, getting into their structure and biochemistry until the uric acid formation.
The Multiple Roles of Urocanic Acid in Health and Disease
Journal of Investigative Dermatology, 2020
Trans-urocanic acid (trans-UCA) is synthesized in the skin, liver, and brain. It is a major natural moisturizing factor in skin and maintains its acid pH. In skin, it isomerizes to cis-UCA following exposure to UVR. Both isomers fulfill multiple roles in health and disease. Cis-UCA has immunomodulatory properties linked with several cutaneous diseases such as skin cancer, atopic dermatitis, and urticaria and associates with systemic diseases including multiple sclerosis. The levels of UCA in the skin, brain, urine, and feces reflect some physiological processes and may be disease biomarkers. Both isomers of UCA have therapeutic potential for a range of disorders.
Functionalities of Purines in Health and Disease
2019
Purines conduct several vital cellular functions as in the production of the numericprecursors of nucleic acids, whereas excess formation of uric acid generated from purines metabolism has been expansively implicated in human disease. The physiological functions and pathogenic attributes of uric acid have been linked to the imminent presentations of cardiovascular abnormalities, diabetes and stroke. Inasmuch as the overproduction of uric acid results in gout, it is established that uric acid constitutes a potent antioxidant in the shielding of DNA from single-strand breaks due to free radicals culminating in a protective effect in neurodegenerative disorders for an extended life span. Thus, this paper describes certain contronymic effects in the functionalities of purines in health and disease.
Uric acid: from a biological advantage to a potential danger. A focus on cardiovascular effects
Vascular Pharmacology, 2019
Non-communicable diseases represent nowadays the most common cause of death worldwide, having largely overcome infectious diseases. Among them, cardiovascular diseases constitute the majority. Given these premise, great efforts have been made by scientific societies to emphasize the fundamental role of cardiovascular prevention and risk factors control. In addition to classical cardiovascular risk factors such as smoking, arterial hypertension, hypercholesterolemia and male gender, new risk factors are emerging from international literature. Among them, uric acid is the protagonist. Several evidences show a direct role of hyperuricemia in the determinism of metabolic and vascular disorders. From the other hand, some researchers have demonstrated that uric ac id is only a marker of cardiovascular damage and not a risk factor for its development. Aim of this review is to evaluate the scientific evidences on the role of uric acid in cardiovascular diseases in order to shed light on this confusing topic.
Both gout and osteoarthritis (OA) are common forms of arthritis that inflict a huge burden to an aging population with the increasing prevalence of obesity. Clinicians have long observed the link between these two conditions. In this review, we summarize the evidence from epidemiologic and immunological studies that described the possible relationship between the two conditions. The recent new understanding on monosodium uric acid crystal-induced inflammation has given insight into probable shared pathogenesis pathways for both conditions. We describe the potential therapeutic implications, particularly regarding the possibility of repurposing traditional gout medications for use in OA.
Uric Acid and Oxidative Stress
Current Pharmaceutical Design, 2005
U'c acid is the final product of purine metabolism in humans. The final two reactions of its production catalyzingthe conversion ofhypoxanthineto xanthine and the latter.to uric.acid are catalysed by the enzyme xanthine oxidoreductme, which may attaln tlvo rnter-convertible forms, namely xanthine dehydrogenase or xanthine oxidase The latter uses molecular oxygen as electron acceptor and generates superoxide anion and other reactive oxygen products The role of uric acid in conditions associated with o;idative stress is not entirely clear. Evidence mainly based on epidemiotogical studies suggests that increased serum levels of uric acid are a risk factor for cardiovascular disease where oxidative stress plays an important pathophysiological role. Also, allopurinol, a xanthine oxidoreductase inhibitor that lowers serum levels of uric acid exerts protective;ffects in situations associated with oxidative stress (e g ischaemiareperfusion in1ury, cardiovascular disease). However, there is increasing experimental and clinical evidence showing that uric acid has an important role in vivo as an antioxidant'
Review of Concepts and Controversies of Uric Acid as Antioxidant and Pro-Oxidant
Uric acid, the end product of purine catabolism in humans and is known for its crystal deposition at higher concentrations (>7 mg/dl) in gout. Less is known about its antioxidant property and the beneficial effects in various diseases. It is thought that high concentration of uric acid in humans is an evolutionary advantage and it is also hypothesized that high concentration of uric acid is to compensate the antioxidant capacity of ascorbic acid which is lost in humans during the course of evolution. In the extracelluar environment, uric acid can scavenge free radicals like hydroxyl radical, singlet oxygen and peroxynitrite radical therefore, it is considered as a powerful antioxidant. On the other hand uric acid depending upon the chemical milieu, changing its property and at times it acts as pro oxidant and is associated with the pathobiochemistry in developing various diseases like hypertension, cardio vascular diseases, ischemia reperfusion injury, diabetes mellitus, non alcoholic fatty liver disorders etc. In this review, we tried to summarize the evolutionary advantages of hyperuricaemia, effects of both antioxidant property and pro-oxidant nature of uric acid in various disease conditions.