W11 Nucleic Acid Metabolism Flashcards
difference between purines and pyrimidines
pyrimidines: one ring, 2 N
purine: two rings, 3 N
difference between ribose and deoxyribose
ribose: C2 has OH
deoxyribose: C2 no OH, just H
role of nucleotides in metabolism
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
how are two nucleotides formed
5-phosphate group of one nucleotide joined to 3-hydroxyl group of next nucleotide > phosphodiester linkage
two types of biosynthesis of purines and pyrimidines
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
important precursors for biosynthesis of purines and pyrimidines
phosphorybosyl pyrophosphate (PRPP)
carbamoyl phosphate
amino acids: glycine, aspartate and glutamine
difference in synthesising purine and pyrimidine
purine: purine ring is built atom by atom on the ribose base
pyrimidine: ribose base is attached after the pyrimidine ring is formed
how is 5-phospho-alpha-D-ribosyl-1-pyrophosphate (PRPP) formed to become intermediate for synthesis of purines and pyrimidines
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
first step of de novo synthesis of purine
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
second step of synthesis of purine
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
last step of synthesis of purines
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
how is adenylate (AMP) produced from IMP
adenylosuccinate synthetase uses GTP for hydrolysis between aspartate and IMP > adenylosuccinate
adenylosuccinate lyase cleaves fumarate from adenylosuccinate > AMP
how is guanylate (GMP) formed from IMP
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
how are AMP and GMP converted into ATP and GTP
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
salvage pathways for synthesis of pyrimidines and purines
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
what are the 4 enzymes that are regulated in purine synthesis
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
what happens during excessive accumulation of uric acid
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
how does defect is PRPP synthetase and PRPP amidotransferase leads to gout
defects in enzymes > insensitive to feedback inhibition by purine nucleotides > purine nucleotides overproduced > excessive uric acid synthesis > gout
how is gout treated
by allopurinol, a substrate analog inhibiter of xanthine oxidase
what is lesch-nyhan syndrome
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
first step of pyrimidine synthesis
CPSII in cytosol uses 2 ATP to catalyse formation of carbamoyl phosphate from glutamine and bicarbonate with the release of glutamate
difference between CPS I and CPSII
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
difference in regulation of pyrimidine biosynthesis between bacteria and animals
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
what happens during degradation of pyrimidines
catabolism of cytosine and uracil > beta alanine, ammonium ion and CO2
catabolism of thymine > beta aminoisobutyric acid, ammonium ion and CO2
how are ribonucleotides used as precursors for dioxyribonucleotides
ribonucleotide reductase reduces ribose to deoxyribose by replacing C2 OH with hydride ion and converts uracil to thymine
