Physiological functions and pathogenic potential of uric acid: A review

Abstract

Uric acid is synthesized mainly in the liver, intestines and the vascular endothelium as the end product of an exogenous pool of purines, and endogenously from damaged, dying and dead cells, whereby nucleic acids, adenine and guanine, are degraded into uric acid. Mentioning uric acid generates dread because it is the established etiological agent of the severe, acute and chronic inflammatory arthritis, gout and is implicated in the initiation and progress of the metabolic syndrome. Yet, uric acid is the predominant anti-oxidant molecule in plasma and is necessary and sufficient for induction of type 2 immune responses. These properties may explain its protective potential in neurological and infectious diseases, mainly schistosomiasis. The pivotal protective potential of uric acid against blood-borne pathogens and neurological and autoimmune diseases is yet to be established.

Keywords: Arachidonic acid; Gout; Metabolic syndrome; Schistosomiasis vaccine; Type 2 cytokines; Uric acid.

Graphical abstract

Fig. 1

The most alarming step . Uric acid, C₅H₄N₄O₃, 7,9-dihydro-1 H-purine-2,6,8(3 H)-trione, molecular mass 168 Da, is a product of the metabolic breakdown of purine nucleotides (adenine and guanine). Crystals of monosodium urate (MSU) in the joints stimulate the inflammasome, NLRP3. The leucine rich repeat (LRR) at the carboxyl end of NLRP3 is the sensor for pathogen- (PAMP), or danger (DAMP)-associated molecular patterns generated by exposure to MSU. Ligand binding leads to the receptor oligodimerization and allows the amino terminal pyrin (PYD) domain to interact with adaptor ASC, which recruits pro-caspase-1 via its card domain and autoactivates it. The active cysteine peptidase processes the IL-1β precursor (pro-IL-1β), which is then ready to exit the cell as biologically active proinflammatory, 17 kDa IL-1β.