Lightbody Lecture 20 Flashcards Preview

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Flashcards in Lightbody Lecture 20 Deck (23):

degrad of purines

DNA and RNA digested to free bases by panc enz's and abs in intestine; most ingested NAs are degraded to uric acid, excreted; inside cells, DNA and RNA deg'd to free bases, but reutilized; free bases used via salvage or converted to uric acid and excreted in urine; not used for E


xanthine oxidase

degrad of guanine nts; cont 2FAD, 2 molybdenum and 8 Fe; xanthine + H2O + O2 --> uric acid + H2O2; not mixed fxn oxygenase; O2 comes from H2O


degrad of adenine nts

adenosine deaminase converts adenosine and deoxyadenosine to inosine --> hypoxanthine thru salvage path (HGPRT) to AMP or to uric acid thru xanthine oxidase



purine metab disease; affects joint of big toe but also feet, ankles, knees, hands, wrists; joint is hot, swollen, red, tender (inflam); 5-10d, then subside; chronic -->hard lumps of urate around joint, dec kidney fxn, kidney stones


gout physio causes

urate crystals accum around joint causing inflam, resulting when [uric acid] in blood > certain []; high [] from excess synth or dec excretion by kidneys (high serum urate)


gout causes

purine-rich diet (red meat, organ meats, yeasts); inc purine degrad; inc PRPP synthetase activity (inc purine synth and degrad, so inc urate prod); decreased/partial HGPRT activity, so inc HX and G, excess caffeine and alcohol; lead - urate excretion


gout treatment

increase fluids, diet (dec foods w/high [purine]), medication anti-inflam, allopurinol)



inhib xanthine oxidase, so can't make uric acid from xanthine; allevs excess uric acid prod in Lesch-Nyhan pts, but doesn't remedy neuro problems



inherited disorders of imm sys-->malfxn of both B and T cells; most common is adenosine deaminase (ADA) def; kids w/ADA def have non-fxning imm sys


adenosine deaminase rxn

adenosine-->inosine-->uric acid


adenosine deaminase deficiency

inhib ribonucleotide reductase; no DNA synth, no uric acid (can't form deoxyadenosine, etc.; deoxyad gets rephos to dAMP, then to dADP and then dATP which inhibits rib reductase


treatment of ADA deficiency

bone marrow; enz replacement therapy, gene therapy


de novo synth of pyrimidines

synth before attach to ribose 5P, unlike purine synth; sources of atoms are Gln, CO2, Asp; 1st 3 enz activities are CAD, last two are UMP synthase


step 1: synth of carbamoyl P

Gln and HCO3- condense in presence of ATP; carbamoyl P synthetase exists in CPS-1 (mito enz, dedicated to urea cycle and Arg biosynth) and CPSII, a cytosolic enz in synth of pyrimidines



major site of regul in animals; UDP and UTP inhibit enz, ATP and PRPP activate it; uses Gln (CPS I uses ammonia (urea cycle))


first 3 rxns

CAD; allows channeling of substs and prods b/w As w/o releasing them to medium (where could be deg'd); channeling inc's overall rate of multistep processes


dihydroorotate dehydrogenase

irrev; dihydroorotate to orotate; oxid pwr derived from quinones (thru coenz Q)


UMP synthase

last two rxns


orotic aciduria

inherited; def in multifxnal enz that cats last 2 rxns, resulting in large amts of orotic acid in urine, retarded growth and severe megaloblastic anemia; treat by admin of uridine and/or cytidine



suicide inhib of thymidylate synthase; from flurorouridine; used in breast, colorectal, gastric, uterine cancers; CTP-->CDP-->dCDP; prevents TM/D/TP from being prod


salvage path for pyrimidines

uridine + ATP --> UMP + ADP (uridine kinase); also thymidine kinase and cytidine kinase (w/ATP, forms xMP + ADP each time)


thymidine kinase

thymidine + ATP w/TK --> ADP + TMP --> TDP --> TTP --> DNA; herpes TK will phos guanine analog acyclovir, further phos to GTP; herpex TK has 3000x greater affin for acyclovir than human TK;



potent inhib of DNA polymerase; herpes DNA polym has 100x greater affin for acyclovir than human; guanine base of acyclovir works as well as thymidine b/c lack spec by enz