W11 Nucleic Acid Metabolism

Question 1

difference between purines and pyrimidines

Answer 1

pyrimidines: one ring, 2 N

purine: two rings, 3 N

Question 2

difference between ribose and deoxyribose

Answer 2

ribose: C2 has OH

deoxyribose: C2 no OH, just H

Question 3

role of nucleotides in metabolism

Answer 3

precursors of dna and rna: purines and pyrimidines

carriers of chemical energy: atp and gtp

cofactors: NAD, FAD CoA, S-adenosyl methione

activated intermediates: UDP-glucose

second messengers: cAMP, cGMP

Question 4

how are two nucleotides formed

Answer 4

5-phosphate group of one nucleotide joined to 3-hydroxyl group of next nucleotide > phosphodiester linkage

Question 5

two types of biosynthesis of purines and pyrimidines

Answer 5

salvage pathways: recycle of free bases and nucleotides released from nucleic acid breakdown

de novo pathways: using metabolic precursors such as amino acids, ribose-5-phosphate, CO2 and NH3

Question 6

important precursors for biosynthesis of purines and pyrimidines

Answer 6

phosphorybosyl pyrophosphate (PRPP)

carbamoyl phosphate

amino acids: glycine, aspartate and glutamine

Question 7

difference in synthesising purine and pyrimidine

Answer 7

purine: purine ring is built atom by atom on the ribose base

pyrimidine: ribose base is attached after the pyrimidine ring is formed

Question 8

how is 5-phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) formed to become intermediate for synthesis of purines and pyrimidines

Answer 8

nucleophilic attack of O on C1 of ribose-5-phosphate (R5P) on beta phosphate of ATP > cleavage of pyrophosphate > release AMP > pyrophosphate immediately attached to O on C1 of R5P

reaction catalysed by ribose-phosphate diphosphokinase

Question 9

first step of de novo synthesis of purine

Answer 9

glutamine phosphoribosyl amidotransferase transfers amino group from glutamine to C1 of PRPP > release glutamate and pyrophosphate > produce 5-phosphoribosyl-1-amine

availability of substrate PRPP is major determinant of rate of this reaction

Question 10

second step of synthesis of purine

Answer 10

phosphoribosylglycinamide synthetase catalyses condensation between glycine carboxylic acid group with 1’-aminoi group of phosphoribosyl 1-amine > 2 carbon atoms and one nitrogen atom from glycine attached to amino group of phosphoribosyl 1-amine > produce glycinamide ribosyl 5-phosphate

Question 11

last step of synthesis of purines

Answer 11

many steps involving C8 of N10-formyl-FH4, glutamine, CO2, aspartate and C2 of N10-formyl-FH4 to form inosine monophosphate (IIMP) > used to form adenine and guanine nucleotides

Question 12

how is adenylate (AMP) produced from IMP

Answer 12

adenylosuccinate synthetase uses GTP for hydrolysis between aspartate and IMP > adenylosuccinate

adenylosuccinate lyase cleaves fumarate from adenylosuccinate > AMP

Question 13

how is guanylate (GMP) formed from IMP

Answer 13

IMP dehydrogenase uses NAD+ for oxidation of IMP to form xanthylate (XMP)

XMP glutamine amidotransferase uses ATP for hydrolysis of XMP with glutamine > release glutamate and GMP

Question 14

how are AMP and GMP converted into ATP and GTP

Answer 14

adenylate kinase and guanylate kinase uses ATP to form ADP from AMP and GDP from GMP respectively

oxidative phosphorylation converts ADP into ATP during respiration

ATP serves as phosphoryl donor for GDP via nucleoside diphosphate kinase to produce GTP

Question 15

salvage pathways for synthesis of pyrimidines and purines

Answer 15

nucleic acids break down > release adenine and guanine

adenosine phosphoribzosyltransferase recycles adenine into AMP

hypoxanthine-guanine phosphoribzosyltransferase recycles guanine and hypoxanthine into GMP and IMP

Question 16

what are the 4 enzymes that are regulated in purine synthesis

Answer 16

PRPP synthetase: inhibited by ADP

PRPP amidotransferase: inhibited by AMP, GMP and IMP

adenylosuccinate synthetase: inhibited by AMP

IMP dehydrogenase: inhibited by GMP

first two enzymes regulate IMP synthesis, last 2 regulate production of AMP and GMP respectively

Question 17

what happens during excessive accumulation of uric acid

Answer 17

uric acid usually converted into allantoin by urate oxidase > converted to allantoic acid > converted to glycoxylic acid and urea

when urate oxidase not functioning at proper levels > uric acid accumulation > hyperuricemia/gout

Question 18

how does defect is PRPP synthetase and PRPP amidotransferase leads to gout

Answer 18

defects in enzymes > insensitive to feedback inhibition by purine nucleotides > purine nucleotides overproduced > excessive uric acid synthesis > gout

Question 19

how is gout treated

Answer 19

by allopurinol, a substrate analog inhibiter of xanthine oxidase

Question 20

what is lesch-nyhan syndrome

Answer 20

complete absence or severe deficiency of HGPRT enzyme activity > severe gouty arthritis

structural gene for HGPRT located on X chromosome > disease is congenital, recessive, sex-linked trait manifested only in males

absence of HGPRT > de novo purine biosynthesis dramatically increased > uric acid level in blood elevated

Question 21

first step of pyrimidine synthesis

Answer 21

CPSII in cytosol uses 2 ATP to catalyse formation of carbamoyl phosphate from glutamine and bicarbonate with the release of glutamate

Question 22

difference between CPS I and CPSII

Answer 22

pathway: urea cycle for I, pyrimidine synthesis for II

source of nitrogen: NH4+ for I, glutamine for II

location: mitochondria for I, cytosol for II

activator: NAG for I, PRPP for II

inhibitor: none for I, UTP for II

Question 23

difference in regulation of pyrimidine biosynthesis between bacteria and animals

Answer 23

bacteria: CTP inhibits ATCase > inhibit formation of carbamoyl-aspartate from carbamoyl-phosphate; positively regulated by ATP

animals: UDP and UTP inhibits CPS II > inhibit formation of carbamoyl-phosphate; positively regulated by ATP and PRPP

Question 24

what happens during degradation of pyrimidines

Answer 24

catabolism of cytosine and uracil > beta alanine, ammonium ion and CO2

catabolism of thymine > beta aminoisobutyric acid, ammonium ion and CO2

Question 25

how are ribonucleotides used as precursors for dioxyribonucleotides

Answer 25

ribonucleotide reductase reduces ribose to deoxyribose by replacing C2 OH with hydride ion and converts uracil to thymine