Lightbody Lecture 20

Question 1

degrad of purines

Answer 1

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

Question 2

xanthine oxidase

Answer 2

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

Question 3

degrad of adenine nts

Answer 3

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

Question 4

gout

Answer 4

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

Question 5

gout physio causes

Answer 5

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)

Question 6

gout causes

Answer 6

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

Question 7

gout treatment

Answer 7

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

Question 8

allopurinol

Answer 8

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

Question 9

SCIDS

Answer 9

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

Question 10

adenosine deaminase rxn

Answer 10

adenosine–>inosine–>uric acid

Question 11

adenosine deaminase deficiency

Answer 11

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

Question 12

treatment of ADA deficiency

Answer 12

bone marrow; enz replacement therapy, gene therapy

Question 13

de novo synth of pyrimidines

Answer 13

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

Question 14

step 1: synth of carbamoyl P

Answer 14

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

Question 15

CPS II

Answer 15

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

Question 16

first 3 rxns

Answer 16

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

Question 17

dihydroorotate dehydrogenase

Answer 17

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

Question 18

UMP synthase

Answer 18

last two rxns

Question 19

orotic aciduria

Answer 19

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

Question 20

FdUMP

Answer 20

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

Question 21

salvage path for pyrimidines

Answer 21

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

Question 22

thymidine kinase

Answer 22

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;

Question 23

acycloGTP

Answer 23

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