Sodium urates

The removal and reduction of the nucleic acid content of various SCPs is achieved by chemical treatment with sodium hydroxide solution or high salt solution (10%). As a result, crystals of sodium urate form and are removed from the SCP solution.16,17 The quality of SCP can be upgraded by the destruction of cell walls. That may enhance the digestibility of SCP. With chemical treatment the nucleic acid content of SCP is reduced. 

Humans catabolize purines to uric acid (pA 5.8), present as the relatively insoluble acid at acidic pH or as its more soluble sodium urate salt at a pH near neutrality. Urate crystals are diagnostic of gout. Other disorders of purine catabolism include Lesch-Nyhan syndrome, von Gierke s disease, and hypo-uricemias. 

Tophi Chalky deposits of sodium urate occurring in gout. Tophi form most often around joints in cartilage, bone, bursae, and subcutaneous tissue and in the external ear, producing a chronic, foreign-body inflammatory response. If untreated, tophi can lead to joint deformity or destruction. 

About two-thirds of the uric acid produced each day is excreted in the urine. The remainder is eliminated through the GI tract after enzymatic degradation by colonic bacteria. A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. 

The presence of sodium urate in the amorphous deposits in a jug found in 1903, but dating back to the Middle Ages, suggests that it was used to store urine, from which the urate precipitated as the urine evaporated. But why was urine stored in a jug in the Middle Ages Perhaps because drinking urine was highly recommended at this time for treatment of bubonic plague and other diseases Lancet, July 11, 1942). 

Gout increased uric acid resulting in sodium urate crystals deposited in the joints... 

Hyperuricemia and chronic or episodic joint pain due to deposition of sodium urate crystals and consequent inflammation (gouty arthritis) are the hallmarks of gout. 

The joints of the hands and feet are prone to accumulation of crystals because of reduced solubility of sodium urate at the slightly cooler temperature of the extremities. 

The excess purines are degraded to uric acid causing increased biood ieveis of this metaboiite (hyperuricemia) and deposition of sodium urate crystais in the Joints and kidneys. 

Gout. An inherited metabolic disorder occurring especially in men, characterized by a raised but variable blood uric acid level, recurrent acute arthritis of sudden onset, deposition of crystalline sodium urate in connective tissues and articular cartilage, and progressive chronic arthritis. 

If properly controlled, simple gout may have few adverse effects. However, the severe neurological symptoms of Lesch-Nyhan syndrome (Section E,2 of text)6 cannot be corrected by medication. Colchicine (Box 7-D), in a manner which is not understood, alleviates the painful symptoms of gout caused by the deposits of sodium urate in joints and tissues. It is also important to keep the dietary purine intake low and it is often necessary to inhibit xanthine oxidase. A widely used and effective inhibitor is the isomer of hypoxanthine known as allopurinol, which is taken daily in amounts of 100 -600 mg or more. 

Habib MJ, Hasker AF. Complex formation between metronidazole and sodium urate effect on photodegradation of metronidazole. Pharm Res 1989 6 58-61. 

Uric acid (Fig. 6) is the main nitrogenous waste product of uricotelic organisms (reptiles, birds and insects), but is also formed in ureotelic organisms from the breakdown of the purine bases from DNA and RNA (see Topics FI and Gl). Some individuals have a high serum level of sodium urate (the predominant form of uric acid at neutral pH) which can lead to crystals of this compound being deposited in the joints and kidneys, a condition known as gout, a type of arthritis characterized by extremely painful joints. 

Gout is a metabolic disease in which there is a overproduction of purines. It is characterized by intermittent attacks of acute arthritis produced by the deposition of sodium urate crystals in the synovial tissue of joints. Drugs used for treating gout are allopurinol, probenecid, colchicine, and NSAIDs. 

Patients with Lesch-Nyhan syndrome may also suffer from gout, which is due to an accumulation of urate in the body with deposition of crystals of sodium urate in the joints and kidneys. However, gout more commonly occurs due to failure of urate excretion by the kidneys, or due to accumulation of P-Rib-PP for reasons other than a deficiency of HG-PRTase. 

Figure 11 Zero-order photodegradation of metronidazole in phosphate buffer of pH 7. without sodium urate O with sodium urate. Source From Ref. 68.

Table 4 Effect of Source and Sodium Urate on the Photodegradation of Metronidazole...

Sodium urate, 5.3x10- M in pH 7.0 phosphate buffer. Source-. From Ref. 68. 

Uric acid in very low concentrations, very strongly absorbs UV radiation and for this reason, has been used to protect various FD C colors against fading when they will be probably exposed to direct sunlight (112). Uric acid has been found to enhance the photostability of solutions of colchicine (70) and FD C Blue No. 2 (82,113). Sodium urate, the neutral salt of uric acid, has a photoprotective effect on solutions of metronidazole (68), doxorubicin hydrochloride (77), and physostigmine sulfate (108). In addition to its photon-absorbing property, uric acid has been reported to also possess antioxidant quality (114). 

Complex formation between metronidazole and sodium urate is responsible for the photostabilization of metronidazole (68). Asker and Islam (72) found that the enhanced photostability of phenobarbital was due primarily to the complex formation between thiosulfate ion and phenobarbital. The complexation of nimodipine with cyclodextrins was found by Mielcarek (129) to significantly reduce its rate of photodegradation. 

Figure 25.18. Urate Crystals. Micrograph of sodium urate crystals. Joints and kidneys are damaged by these crystals in gout. [Courtesy of Dr. James McGuire.]...

Molecular model of uric acid. Uric acid is essential to the digestive process. If the body produces too much uric acid or if not enough is excreted, however, high levels of uric acid in the blood can lead to crystals of sodium urate being concentrated in the joints and tendons. These cause the inflammation, pressure, and severe pain associated with gouty arthritis, or gout. 

Allopurinol, which affects both the penultimate and ultimate steps in the production of uric acid, is used to lower plasma uric acid levels in conditions associated with excessive urate production (e.g., gout, hematologic disorders, and antineoplastic therapy). Sodium urate has a... 

A second aspect of the precipitation of acute attacks of gout is related to the inflammatory reaction produced by the injection of sodium urate crystals. The historical background for believing that such materials are related to the occurrence of acute attacks is reviewed by McCarty (MIO). Since synovial fluid from patients with acute attacks contains micro-crystalline sodium urate, it appeared reasonable to believe that the presence of these crystals would cause gouty attacks. A number of investigators showed that administration of a microcrystalline sodium urate resulted in attacks in normal human subjects, in dogs, and in gouty patients in a quiescent phase (FI, H12, M4). 

A condition known as pseudogout has been investigated by Kohn et al. (K12). Clinically, their patients appeared to have gouty arthritis. However, the serum urate levels were normal. When fluid from these patients was removed, it was found to contain crystals that were not sodium urate but calcium pyrophosphate. The mechanistic parallels to gout are obvious. 

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