Purine Degradation and Salvage (Gout, Lesch-Nyhan) - CRASH! Medical Review Series

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(Disclaimer: The medical information contained herein is intended for physician medical licensing exam review purposes only, and are not intended for diagnosis of any illness. If you think you may be suffering from any medical condition, you should consult your physician or seek immediate medical attention.)

[@woloabel]

In the Matter of Purine Degradation and Salvage (Recycle of Nucleotides of Purine): 1) Purine Degradation is the kinetics of Amino Acids and Precursors or Catabolism of Purines to Excretable Products, namely Uric Acid. In this process A) Phosphoribosyl Pyrophosphate (PRPP) to B) Inosine-5-monophosphate (IMP of Purine Synthesis) to C) Inosine to D) Hypoxanthine in reaction with Xanthine Oxidase forms E) Xanthine in reaction with Xanthine Oxidase once more goes to F) Uric Acid, the product that is excreted within Urine. Adenosine Degradation: 1) Nucleotide Adenosine Monophosphate (AMP) can go to IMP and Adenosine reacting with Adenosine Deaminase (ADA) can go to Inosine. For Guanosine Monophosphate (GMP) Degradation: 1) GMP; 2) Guanosine; 3) Guanine to 4) Uric Acid. In Regards to Salvage (Reconjugation of Subtrates) of Purines: 1) Hypoxanthine to IMP and 2) Guanine to GMP via Hypoxanthine Guanine Phosphoribosyltransferase (HGPRT). In Regards to Pathology of Metabolism of Purines: 1) Lesch Nyhan Syndrome (XLR; Males Exclusively) occurs when Congenital Enzyme Deficiency is of HGRPT Enzyme (Neuropsychiatric Signs Common: 1) Motor Dysfunction 2) Intellectual Disability, 3) Self Mutilation, and 4) Behavior Disturbances). 2) ADA Deficiency (Autosomal Recessive) is understandably the Congenital Deficiency of ADA Enzyme marked by a Clinical Setting (Prone to Microorganismal/Viral Infections) of Severe Combined Immunodeficiency (SCID). Laboratories can elucidate this pathology by the Elevation of Precursor Products (Adenosine Elevation in the Serum). 3) Gout (Idiopathic Aetiology of Underexcretion [or Renal Failure] or Overproduction) where Monosodium Urate (MSU) Crystals Deposit within the Joints (Tophi: Fibrosis and Giant Cell Morphology) causing Arthritis. Risk Factors For Gout are 1) Meat Consumption, 2) Alcohol Consumption, 3) Age (0ld) and 4) Male Gender. Overproduction Gout can occur with 1) Myeloproliferative Disease (MPD), 2) Tumor Lysis Syndrome (TLS), 3) and Lesch Nyhan Syndrome. For the Pharmacology of Gout: 1) Allopurinol Inhibits the Production of Uric Acid by inhibiting Xanthine Oxidase (XO) for overproduction of Uric Acid. 2) Febuxostat (Trade Name Uloric) has the identical Mechanism. 3) Probenacid acts to increase the Uric Acid Secretion (Underexcretion Aetiology of Gout) and 4) Rasburicase or Recombinant Urate Oxidase also increases Uric Acid Secretion by converting Uric Acid to Allantoin, a more excretable Metabolite. Furthermore, it is useful to understand Folate (Vitamin B9) is Essential not only to Animals and Humans (Eukaryotes) but all of Life organisms (Prokaryotes and Protista). For Bacteria (Prokaryotes) the Metabolism or synthesis of Folate is different: 1) Pteridine is Combined with P-Aminobenzoic Acid (PABA) with an Enzyme Dihydropterate Synthetase along with Glutamine to Synthesize Folate and bDHFR (Enzyme particular to Bacteria) to active Folate, THF. The Antimicrobials 1) Sulfonamides and 2) Trimethoprim are Metabolic Pathway Inhibitors Drug Class which Antagonize or Inhibit Dihydropterate Synthase and bDHFR respectively. Bacterial Infections can be treated with Sulfamethoxazole-Trimethoprim via this Mechanism of Action especially when other Antibiotics are ineffective or counterindicated (Hypersensitivity to Penicillins or Beta Lactams). Goodness, I have just noticed my first Congenital Lesch Nyhan Syndrome Subject who presented with an elevated Uric Acid in Urine and various Gout Episodes (Positive Birefringent Needle Shaped Crystals) and Pseudogout because of Calcium Pyrophosphate Crystals due to Calcium Pyrophosphate Deposition Disease (CPDD). He is doing well with Anti Gout Drug Colchicine and an Xanthine Oxidase Inhibitor. Just kidding. He needs Percutaneous Nephrolithotomy. MD Paul Bolin, du bist gesunder Verstand!

[@Sam_1964]

Outstanding presentation

[@Redrose-jk5jz]

Thanks, keep it up

[@TheGtagtr]

Paul, are you a doctor