Purine Metabolism Essay
Purine metabolism is central to the production of nucleotides in the body. Imbalances in this process can lead to hyperuricemia which is abnormally high levels of uric acid in the blood [>360μmol/L in females and >400μmol/L in males]. Hyperuricemia can lead to uric acid crystals precipitating in the joints, skin, vessels and other tissues, this is a form of inflammatory arthritis known as gout. Uric acid is a metabolite of purine metabolism therefore gout can aptly be characterized as a disorder of purine metabolism.
The disorder has a myriad of causes including those relating to both genetics and diet.
In terms of diet, the excessive consumption of purine-rich foods can lead to and increased production of uric acid due to increased purine metabolism, …show more content…
Since there is a reduced salvage of guanine and hypoxanthine, it leads to increased uric acid production, hyperuricemia and eventually gout.
PRPP synthetase is an enzyme responsible for the synthesis of activated ribose, this enzyme is used during the de novo synthesis of purines and pyrimidines. This enzyme is allosterically regulated and its activity is affected by three distinct genes: PRPS1, PRPS2 and PRPS1L1. Mutations in these genes leads to increased production of PRPP. Thus, excess purine nucleotides are being formed which leads to increased purine metabolism resulting in enhanced production of uric acid and as a consequence hyperuricemia and gout.
A glucose 6- phosphatase deficiency can result in Von Gierke disease. The inability to dephosphorylate glucose 6-phosphate leads to an increased activity in the pentose phosphate pathway. Enchanced production of ribose 5 phosphate results in substrate level activation of PRPP synthase. This in turn, as described above, can lead to hyperuricemia and
The disorder has a myriad of causes including those relating to both genetics and diet.
In terms of diet, the excessive consumption of purine-rich foods can lead to and increased production of uric acid due to increased purine metabolism, …show more content…
Since there is a reduced salvage of guanine and hypoxanthine, it leads to increased uric acid production, hyperuricemia and eventually gout.
PRPP synthetase is an enzyme responsible for the synthesis of activated ribose, this enzyme is used during the de novo synthesis of purines and pyrimidines. This enzyme is allosterically regulated and its activity is affected by three distinct genes: PRPS1, PRPS2 and PRPS1L1. Mutations in these genes leads to increased production of PRPP. Thus, excess purine nucleotides are being formed which leads to increased purine metabolism resulting in enhanced production of uric acid and as a consequence hyperuricemia and gout.
A glucose 6- phosphatase deficiency can result in Von Gierke disease. The inability to dephosphorylate glucose 6-phosphate leads to an increased activity in the pentose phosphate pathway. Enchanced production of ribose 5 phosphate results in substrate level activation of PRPP synthase. This in turn, as described above, can lead to hyperuricemia and