BMSC 230-MODULE 13 EXAM
QUESTIONS AND ANSWERS
contributors of atoms to the purine ring - ANSWER-glutamate, glutamine, aspartate,
CO2, formate(carried by tetrahydrofolate)
c1 of ribose-5-p where the purine ring is built is unreactive so - ANSWER-ATP
donates a pyrophosphate group to C1=phosphoribosylpyrophosphate
Phosphoribosylpyrophosphate (PRPP) - ANSWER-activated substrate
first purine product of de novo pathway - ANSWER-inosine monophosphate(IMP)
-precursor for AMP and GMP(can be further converted to substrates for RNA and
DNA synthesis(GTP, ATP, dGTP, dATP)
first committed and regulated step of de novo pathway - ANSWER-involves
glutamine-PRPP-amidotransferase which attaches an amino group from glutamine to
ribose sugar = initiates pathway
remaining atoms for IMP synthesis comes from - ANSWER-glutamine, glycine,
aspartate, CO2, N^10-formyl-tetrahydrofolate
-ATP is required
IMP->AMP - ANSWER--aspartate is the amino group donor
-hydrolysis of GTP is required
IMP->GMP - ANSWER--glutamine is the amino group donor
-ATP hydrolysis is required
de novo pathway regulation - ANSWER-primarily through allosteric inhibition of
glutamine-PRPP-amidotransferase by the end products of the pathway(IMP, GMP,
AMP)
-sequential inhibition with GMP and AMP first then IMP
-concerted inhibition with all three products
salvage pathway - ANSWER--purine nucleotide synthesis from existing purine bases
from nucleic acid/nucleotide turnover/degradation
-includes adenosine, guanine, hypoxanthine
-adenine phosphoribosyltransferase(APRT) catalyzes adenine+
phosphoribosylpyrophosphate
-PPi is released
-AMP produced
-hypoxanthine-guanine phosphoribosyltransferase(HGPRT) catalyzes
hypoxanthine/guanine + phosphoribosylpyrophosphate=IMP or GMP
, HPGRT is the major enzyme for - ANSWER-salvaging purines
IMP can be converted to - ANSWER-AMP or GMP
APRT pathway is the minor pathway b/c - ANSWER-most adenine is deaminated
Lesch-Nyhan syndrome - ANSWER-inherited mutation in the gene coding for
HGPRT=reduces its activity
-occurs in 1 in 380,000 births
-gene is on x-chromosome(primarily affects males)
-salvage pathway becomes defected and purine synthesis is now mainly through de
novo
less PRPP used in salvage pathway=more for Gln-PRPP amidotransferase=
increased de novo pathway= - ANSWER-GMP and IMP increases=less inhibition of
de novo pathway
b/c of increased flux through de novo=decreased use of purines= - ANSWER-
increased degradation pathway of purine= increased levels of uric acid=gout
Lesch-Nyhan syndrome symptoms - ANSWER-motor dysfunction, mental
retardation, hostility, compulsive mutilation
-bases of symptoms is not understood as treatments do not stop CNS symptoms
purine degradation - ANSWER-1. phosphate group removed from AMP and
GMP(nucleosides remain)
2. adenosine undergoes deamination=inosine
3. inosine and guanosine have their ribose removed in a hydrolytic rxn=guanine and
hypoxanthine
-hypoxanthine is metabolized to xanthine=uric acid
we naturally secrete uric acid in our...and...is the sodium salt for uric acid -
ANSWER-urine;urate
increased uric acid concentration in blood= - ANSWER-crystallizes and deposits in
joints=pain and inflammation=gout
gout - ANSWER--particularly affects hands and feet
-treatment: 1. diet-limiting meat(very cellullar therefore has increased amounts of
DNA and RNA=increased purine levels) and beer(high in purine)
2. allopurinol(if gout is too severe)
allopurinol - ANSWER--substrate analog of hypoxanthine
-inhibitor of xanthine oxidase(produces uric acid in degradative pathway)
pyrimidine(C,T,U) synthesis - ANSWER--ONLY de novo
-synthesized from atoms from glutamine, CO2, and aspartate
-rate limiting step involves carbamoyl synthetase II
QUESTIONS AND ANSWERS
contributors of atoms to the purine ring - ANSWER-glutamate, glutamine, aspartate,
CO2, formate(carried by tetrahydrofolate)
c1 of ribose-5-p where the purine ring is built is unreactive so - ANSWER-ATP
donates a pyrophosphate group to C1=phosphoribosylpyrophosphate
Phosphoribosylpyrophosphate (PRPP) - ANSWER-activated substrate
first purine product of de novo pathway - ANSWER-inosine monophosphate(IMP)
-precursor for AMP and GMP(can be further converted to substrates for RNA and
DNA synthesis(GTP, ATP, dGTP, dATP)
first committed and regulated step of de novo pathway - ANSWER-involves
glutamine-PRPP-amidotransferase which attaches an amino group from glutamine to
ribose sugar = initiates pathway
remaining atoms for IMP synthesis comes from - ANSWER-glutamine, glycine,
aspartate, CO2, N^10-formyl-tetrahydrofolate
-ATP is required
IMP->AMP - ANSWER--aspartate is the amino group donor
-hydrolysis of GTP is required
IMP->GMP - ANSWER--glutamine is the amino group donor
-ATP hydrolysis is required
de novo pathway regulation - ANSWER-primarily through allosteric inhibition of
glutamine-PRPP-amidotransferase by the end products of the pathway(IMP, GMP,
AMP)
-sequential inhibition with GMP and AMP first then IMP
-concerted inhibition with all three products
salvage pathway - ANSWER--purine nucleotide synthesis from existing purine bases
from nucleic acid/nucleotide turnover/degradation
-includes adenosine, guanine, hypoxanthine
-adenine phosphoribosyltransferase(APRT) catalyzes adenine+
phosphoribosylpyrophosphate
-PPi is released
-AMP produced
-hypoxanthine-guanine phosphoribosyltransferase(HGPRT) catalyzes
hypoxanthine/guanine + phosphoribosylpyrophosphate=IMP or GMP
, HPGRT is the major enzyme for - ANSWER-salvaging purines
IMP can be converted to - ANSWER-AMP or GMP
APRT pathway is the minor pathway b/c - ANSWER-most adenine is deaminated
Lesch-Nyhan syndrome - ANSWER-inherited mutation in the gene coding for
HGPRT=reduces its activity
-occurs in 1 in 380,000 births
-gene is on x-chromosome(primarily affects males)
-salvage pathway becomes defected and purine synthesis is now mainly through de
novo
less PRPP used in salvage pathway=more for Gln-PRPP amidotransferase=
increased de novo pathway= - ANSWER-GMP and IMP increases=less inhibition of
de novo pathway
b/c of increased flux through de novo=decreased use of purines= - ANSWER-
increased degradation pathway of purine= increased levels of uric acid=gout
Lesch-Nyhan syndrome symptoms - ANSWER-motor dysfunction, mental
retardation, hostility, compulsive mutilation
-bases of symptoms is not understood as treatments do not stop CNS symptoms
purine degradation - ANSWER-1. phosphate group removed from AMP and
GMP(nucleosides remain)
2. adenosine undergoes deamination=inosine
3. inosine and guanosine have their ribose removed in a hydrolytic rxn=guanine and
hypoxanthine
-hypoxanthine is metabolized to xanthine=uric acid
we naturally secrete uric acid in our...and...is the sodium salt for uric acid -
ANSWER-urine;urate
increased uric acid concentration in blood= - ANSWER-crystallizes and deposits in
joints=pain and inflammation=gout
gout - ANSWER--particularly affects hands and feet
-treatment: 1. diet-limiting meat(very cellullar therefore has increased amounts of
DNA and RNA=increased purine levels) and beer(high in purine)
2. allopurinol(if gout is too severe)
allopurinol - ANSWER--substrate analog of hypoxanthine
-inhibitor of xanthine oxidase(produces uric acid in degradative pathway)
pyrimidine(C,T,U) synthesis - ANSWER--ONLY de novo
-synthesized from atoms from glutamine, CO2, and aspartate
-rate limiting step involves carbamoyl synthetase II
