Lightbody Lecture 19

Question 1

biol signif of nt metab

Answer 1

nts make up NAs (DNA, RNA); NTPs are E carriers in cells; many metab paths are regul by level of individ nts (cAMP regul of glucose and lipids); adenine nts are cmpnts of many coenz’s (NAD, NADP, FAD, FMN); carriers of activ’d metabs for biosynth (UDP-glucose in glycogen synth); nts (adenosine - inhib nt in brain; regulates pain, flow, resp, sleep)

Question 2

nt synth

Answer 2

all enz’s in cyto; mjr diffs in nt metab b/w bact, viruses, humans form rationale for antibiotics vs antivirals; metab paths of nts (purines and pyrimidines) in 4 sections

Question 3

4 sections of metab paths of nts

Answer 3

de novo synth of nts from basic metabolites; salvage paths that recycle preformed nts; catab paths for excreting nts; path for converting ribonts into deoxyribonts

Question 4

folic acid (B9)

Answer 4

important donors of 1C units for all oxid levels of C except CO2 (uses biotin); humans can’t synth pterin ring, so get fr diet/microorgs; imp in synth of purines and pyrimidines, focal pt for anti-cancer drugs; deficiency in preg–>spina bifida and megaloblastic anemia

Question 5

THF

Answer 5

carries 1C units; methotrexate used in cancer and autoimm and replaces more toxic aminopterin (no CH3 on N10); compet inhib of DHFR (so folic acid can’t –> dihydrofolate)

Question 6

sulfonamides (sulfa drugs)

Answer 6

antibact; humans can’t make folate; bact can’t take up folate from env, need to synth; 1st antibact drugs made; compet inhibs of DHPS - dihydropteroate synthase (compete w/p-amino-benzoic acid to form dihydropteroic acid)

Question 7

purine biosynth

Answer 7

use ribose links PPP to both purine and pyrim biosynth; PRPP (phosphoribosyl pyrophosphate) synthetase - builds purine ring upon ribose; can also use ribose phosphate pyrophosphate kinase (- by AMP, ADP, GDP)

Question 8

MTX (methotrexate)

Answer 8

prevents THF from forming and consequently DNA and RNA synth; used in cancer prevention, but toxic to all dividing cells

Question 9

synth of nucleoside di and triphosphates

Answer 9

to be incorp into DNA and RNS, NMPs must be converted into NTPs

Question 10

nucleoside mono/diphosphate kinase

Answer 10

AMP + ATP 2 ADP; GDP + ATP GTP + ATP

Question 11

NDP kinase

Answer 11

will phosphorylate any nt; phos’s AZT, ns analog that acts as compet inhib to NTPs for reverse transcripatse

Question 12

hypoxanthine

Answer 12

inhibits Gln-PRPP amidotransferase, so ribose5P can’t form IMP or AMP/GMP, etc.

Question 13

ribonucleotide reductase

Answer 13

ribonucleoside diphosphate –> deoxyribonucleoside diphosphate; + by ATP; - by dA/G/CTP or TTP; 2 identical su’s; one AS, 2 sites that reg enz activity; reg site is allosteric site that bds ATP (activ) or dATP (inhib); subst specificity site is allosteric site, det subst spec of enz

Question 14

salvage path for purines

Answer 14

when de novo synth inhib’d, orgs can still survive and grow if source of purine bases are avail fr diet/brkdn of DNA and RNA; parasites rely on paths b/c have lost genes to make nts; resting T lymphos use this path, but when activ’d go to de novo path (in HIV, de novo path blocked, so when activated die); energ cheaper than de novo, used in non-dividing cells

Question 15

purine salvage path

Answer 15

dietary nts don’t contrib E as do carbs, prots, and fats; not incorp into RNA or DNA, but metab to ind cmpnts (bases, sugar, P); cell DNA and RNA degraded to ind bases that can be reconv’d to nts via salvage path; under resting, 90% of purine nts derived fr DNA/RNA brkdn, resynth thru salvage path

Question 16

adenine phosphoribosyltransferase (APRT)

Answer 16

adenine + PRPP AMP + PPi; not v imp bc gen v little adenine b/c catab of adenine is through inosine (part of salvage path)

Question 17

hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

Answer 17

hypoxanthine + PRPP IMP + PPi –> AMP, GMP; or guanine + PRPP GMP + PPi; used pref as long as hypoxanthine is avail; maint of adequate supply of purine nts in tissues where de novo synth is absent inv hypoxanthine salvage using this enz; med by hypoxanthine inhib of amidophosphoribosyl transferase (step 2 of de novo path); part of salvage

Question 18

purine metabolism

Answer 18

hypoxanthine and purine nts inhib 2nd rxn in de novo synth; PRPP–>IMP–>AMP/GMP

Question 19

de novo synth path

Answer 19

PRPP–>GMP in 12 steps, use 7ATP; byproducts–>recycle to precurors, use 17ATP; use 24 ATPs

Question 20

salvage synth of GMP

Answer 20

PRPP –> GMP (1 step, no ATP use)

Question 21

Lesch Nyhan synd

Answer 21

rare X-linked rec disease; boys; def of enz hypoxanthine-guanine phosphoribosyltransferase caused by chrom deletion; pts appear normal at birth, appear in couple months; pts have excessive purine synth–>overprod of uric acid (hyperuricemia, orange crystals in diapers) - gout, kidney stones, neuro and psych abnormalities

Question 22

compulsive self-injurious behavior

Answer 22

2nd year of life; pts become self-mutilating; bite lips, tongues, fingers; feel pain, relieved when protected from selves; aggressive behav twd fam, happy, engaging when restrained; death in 2nd decade b/c renal failure