Purine Metabolism: Uric Acid Synthesis, Degradation, and Associated Disorders, Study Guides, Projects, Research of Biochemistry

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 The end product of purine metabolism in humans is uric acid.  The nucleotide monophosphates (AMP, IMP & GMP) are converted to their respective nucleoside forms (adenosine, inosine & guanosine) by the action of nucleotidase.  The amino group, either from AMP or adenosine, can be removed to produce IMP or ionosine.

 Xanthine oxidase converts hypoxanthine to xanthine & xanthine to uric acid.  This enzyme contains FAD, molybdenum & iron.  It is exclusively found in liver & small intestine.  Xanthine oxidase liberates H2O2 which is harmful to the tissues.  Catalase cleaves H2O2 to H2O & O2.

 It is final excretory product of purine metabolism in humans.  Uric acid can serve as an important antioxidant by getting itself converted (non-enzymatically) to allantoin.  It is believed that the antioxidant role of ascorbic acid in primates is replaced by uric acid.

 Most animals (other than primates) oxidize uric acid by the enzyme uricase to allantoin, where the purine ring is cleaved.  Allantoin is then converted to allantoic acid & excreted in some fishes.  Further degradation of allantoic acid may occur to produce urea (in amphibians, most fishes & some molluscs) & to ammonia (in marine invertebrates).

Uric Acid Allantoin Allantoic acid Urea Ammonia Uricase Allantoinase Allantoicase Urease Glyoxylate

 Hyperuricemia refers to an elevation in the serum uric acid concentration.  This is sometimes associated with increased uric acid excretion (uricosuria).

 It is a metabolic disease associated with overproduction of uric acid.  At the physiological pH, uric acid is found in a more soluble form as sodium urate.  In severe hyperuricemia, crystals of sodium urate get deposited in the soft tissues, particularly in the joints.  Such deposits are commonly known as tophi.

 PRPP synthetase:  In normal circumstances, PRPP synthetase is under feedback control by purine nucleotides (ADP & GDP).  A variant forms of PRPP synthetase-which are not subjected to feedback regulation-leads to the increased production of purines.

 PRPP glutamylamidotransferase:  The lack of feedback control of this enzyme by purine nucleotides also leads to their elevated synthesis.  Deficiency of enzymes of salvage pathway:  HGPRT enzyme of purine salvage pathway & its defect causes Lesch-Nyhan syndrome.  It is associated with increased synthesis of purine nucleotides.

 Glucose- 6 - phosphatase deficiency:  This condition is known as von Gierke's disease (glycogen storage disease, type I)  When this enzyme is deficient, glucose- 6 - phosphate cannot be converted to glucose.  More glucose is channelled into the HMP shunt, resulting in increased availability of ribose- 5 - phosphate.

 This leads to increased formation of PRPP & purine over production.  Elevation of glutathione reductase:  Increased glutathione reductase generates more NADP

which is utilized by HMP shunt.  This causes increased ribose 5 - phosphate & PRPP synthesis