Biochemistry USMLE Step 1 Study Guide with Approved Questions and Answers

Achondroplasia involves what defect? - Cell-signaling defect of fibroblast growth factor (FGF) receptor 3 Marfan's syndrome involves a mutation in what? - Fibril in gene Nucleoside + phosphate= ? - Nucleotide Adenine and Guanine are in what type of nucleic acid? - Purines Cytosine, Uracil and Thyamine arein what kind of nucleic acid? - Pyrimidines Xanthine, hypoxanthine and uric acid are all what type of base? - Purine How many hydrogen bonds are found between Guanine and Cytosine? - 3 Chargaff's ruledictates that the percent of adenine in a DNA molecule is = to the % of _____ in a DNA molecule. - thyamine What is the rate limiting step in Purine de novo synthesis? - PRPP step via glutamin PRPP amidotranferase PRPP amidotransferase inhibited by what downstream products in purine synthesis? - IMP, GMP, AMP and puring analogs Allopurinola and 6-mercaptopurine What are the required cofactors for purine de novo synthesis? - THF, glutamine, glycine, aspartate, CO2 Name two crucial enzymes involved in purine salvage pathways - hypoxanthine Phosoribosyltransferaase (HGPRT) anf Adenosine Deaminase. HGPRT converts guanine to ______ and hypoxanthine to _______. - GMP; IMP Allopurinol and 6-mercaptopurine are purine analogs that inhibit ________. - PRPP amidotransferase Allopurinol is used for the treatment of chronic gout because it __________. - Decreases uric acid levels by blocking xanthine oxidase with converts hypoxanthing to xanthine and then to uric acid Lesch-Nyhan is a X-lined recessive disorder due to __________. - absence of HGPRT--thus patients are unable to salvage purines leading to excessive de novov synthesis which then leads to excess uric acid production. The presentation of retardation, cerebral palsy, slef-mutiliation, gout and "crystals in diaper" and self-muilation is most consistent with ________. - Lesch-Nyahan Syndrome What is the treatment for Lesch-Nyhan syndrome? - Allopurinol (inhibits xanthine oxidase in the purine salvage pathway, thus reducing excesss production of uric acid) What disorder is associated with hyperuricenmis either due to overproduction or underexcretion of uric acis and is charcterized by sodium urate crystal deposits in the joints and soft tissues? - Gout What are some causes of uric acid overproduction in aquired gout? - Leukemia, alcoholism, myelopproliferative syndrom, multiple myeloma, hemolysis, neoplasia, psoriasis What drugs are associated with urate underexcretion in aquired gout? - Aspirin, diuretics, alcohol What is podagra? - Gout of the great toe Monoarticular arthirits of distal joints often with a history of hyperuricemia percipiatated by a sudden change in urate levels (due to large meals, alcohol) is characteristic of ______ and can eventually lead to the formation of _______. - gout; nodular tophi (urate crystals surrounded by fibrous connective tissue) located around the joints and Achilles tendon. How is gout diagnosed? - Detection of negatively bifringent crystals from articular tap, arthritis and hyperuricemia What is the treatment for Gout? - For chronic-allopurinol to lower uric acid levels but NOT for acute treatment. For aute treatment decrease pain and inflammation with colchicines and NSAIDS and avoidance of large meals and ETOH What is colchicine used for and how does it work? - Acute Gout. It prevents neutrophil and leukocyte migration into the joint by binding tubulin, depolarizing microtubules and interefering with motility and degranulation. Note: Indomethacin is more commonly used due to less side effects SCID (Severe Combined T and B Immunodeficieny) is an autsomal recessive disorder cause by a deficiency in what enzyme? - Adenosine deaminse How does a deficeincy in adenosine deaminase cause SCID? - W/ a deficiency in adenosidne deaminase (impt enzyme involved purine synthesis) causes the build up of ATP and dATP which in turn inhibit ribonucleotide reductase thus preventing DNA synthesis and decreasing lymphocyte count. Children with no plasma cells or B or T lymphocytes on CBC and no thymus and recurrent infections (esp. Candida and Pneumocystis jiroveci) are likely to have _______. - SCID What is the treatment for SCID? - Gene therapy and Bone marrow transplant What chemotherapy drug inhibit ribonucleotide reductase (enzyme that converts NTP TO dNTPS)? - hydroxyurea Hereditary Orotic Aciduria is due to ______________. - The inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) and thus orotic acid builds up in urine