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biol signif of nt metab

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)


nt synth

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


4 sections of metab paths of nts

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


folic acid (B9)

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



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)


sulfonamides (sulfa drugs)

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)


purine biosynth

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)


MTX (methotrexate)

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


synth of nucleoside di and triphosphates

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


nucleoside mono/diphosphate kinase



NDP kinase

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



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


ribonucleotide reductase

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


salvage path for purines

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


purine salvage path

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


adenine phosphoribosyltransferase (APRT)

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


hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

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


purine metabolism

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


de novo synth path

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


salvage synth of GMP

PRPP --> GMP (1 step, no ATP use)


Lesch Nyhan synd

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


compulsive self-injurious behavior

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