Purine II

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What is the mechanism of action of Allopurinol?
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What is the mechanism of action of Allopurinol?
It inhibits Xanthine Oxidase enzyme--> Uric acid is not formed in body, Hence it is helpful in patients with hyperuricemia.
A 20-year-old male presents for annual wellness screening examination at your clinic. His laboratory results reveal uric acid levels of 10 mg/dl. ( Normal Value- 3.4-7.2 mg/dl).He is otherwise asymptomatic and all other labs are in normal range. Which is the best drug to treat his hyperuricemia?
Asymptomatic hyperuricemia is not treated with medications.
In which form does uric acid exist in blood pH of 7.4 ?
98% of uric acid exist as Monosodium urate in blood at pH of 7.4
How is uric acid excreted from body?
2/3 of uric acid is excreted by kidney and rest by intestine
A 20-year-old male presents to your clinic for the follow up of Gout. His serum uric acid levels have increased to 10 mg/dl from previous value of 8 mg/dl. ( Normal value is 3.5-7.2 mg/dl). You decide to add citra K to his drug regimen. What is the mechanism of action of Citra K?
Citra k is an oral systemic alkalizer containing potassium citrate and citric acid in a sugar-free base.
Urine alkalizers increased the solubility of uric acid in urine and hence the excretion of urice acid.from body.
Urine alkalizers commonly contain Sodium/Potassium citrate,Sodium bicarbonate. They are also used to reduce burning sensation in urinary tract infections.
What is the effect of changing pH of urine on urinary excretion of uric acid?
Increasing the pH of uric acid increases the solubility of uric acid in urine and hence the excretion of uric acid in urine
A 25-year-old man presents with big inflammed swollen red toe. His serum uric acid levels are increased and synovial fluid aspirate shows needle shaped negative birefringent crystals .Which one of the following conditions can not cause such crystals?

A. Increased Km of PRPP synthetase
b . Deficiency of HGPRT
c. Tumor lysis syndrome
d. Von Gierke disease
e. Increased Vmax of PRPP synthetase
All the causes except A will cause hyperuricemia and hence uric acid crystals. Increased Km of PRPP will decrease the affinity of the enzyme for PRPP and hence slow down denovo synthesis of uric acid and among the choice, least likely cause hyperuricemia.
What is Tumor lysis syndrome?
Tumor lysis syndrome occurs when the tumor cells release their content into blood stream either spontaneously or inresponse to radiation or chemo therapy. It is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia.
A 25-year-old male with past medical history of metastatic prostate cancer was recently treated with chemoradiation. What will be most likely effect on his uric acid levels and why?
He will most likely develop hyperuricemia . Chemoradiation kills tumor cells. Nucleic acids released from tumor cells are degraded. Uric acid is formed from purines degradation.
Why does a patient with Von Gierke disease has hyperuricemia?
Deficiency of Glucose -6-phosphatase ---> Glucose 6- phosphate cannot be degraded into glucose and hence is diverted to PPP pathway--> Increased Ribose- 5-phosphate and PRPP formation---> Increased PPRR increases denovo purine synthesis--> increased purines--> increased degradation or purines--> increased uric acid
Which one of the following does not contribute to uric acid pool in blood? A Salvage pathway of purines B Denovo synthesis of purines C Denovo synthesis of pyrimidines d Diet e Degradation of purinesUric acid is end product of purine metabolism and so C (De-novo synthesis of pyrimidines) does not contribute to uric acid pool.What is negative birefringence (shown by uric acid crystals)When uric acid crystals are viewed under plane polarized light, the crystals lying parallel to polarized light are yellow colored and those lying perpendicular are blue in color.What is Tophi?Tophi is deposition of uric acid crystals in skin , connective tissues of the body. The uric acid is deposited in tendons, ligaments, bursae , cartilage, synovial membranes, soft tissues of the joint and skin.What is Gout ?It is inflammation of joints due to deposition of uric acid crystals.What dietary recommendation would you give a patient with Gout?1) Avoid purine rich foods- meats ( bacon, turkey, veal , venison), seafoods ( sardines , shellfish, scallops etc), organ meats ( liver), Vegetables ( peas, beans and mushrooms,) 2) Avoid alcohol 3) Avoid sugary foods 4) Drink lots of water ( to flush uric acid) 5) Increase fiberHow does lime juice help in hyperuricemia?Lime juice contains citric acid ( urine alkalizer) which helps in flushing out uric acid from body.Why does alcohol/ beer exacerbate the symptoms of hyper uricemia ? or why should gout patient / hyperuricemia patient restrict alcohol intake or1) high purine content of certain beers 2) Ethanol increases lactic acid by increasing NADH/NAD ratio and this increased lactate inhibits renal secretion of uric acid in proximal renal tubules 3) Ethanol accelerates purine nucleotide degradation and increases levels of hypoxanthine and xanthine. 4 ) Ethanol is weak inhibitor of xanthine oxidase ( https://pubmed.ncbi.nlm.nih.gov/15936302/)Which enzyme deficiency causes Lysch Nyhan SyndromeHGPRTTrue or False Lysch Nyhan syndrome occurs exclusively in malesTrue It has X linked recessive inheritance pattern