Nucleotide Flashcards
Purine
Guanine
Adenine
PUR-GA
Pyrimidine
PyCUT
Cytosine
Uracil
Thymine
Nucleoside link
B N glycosidic bond
Purine vs pyrimidine
Ribose 5 phosphate first + ring
Purine
Purine vs pyrimidine
Ring first plus sugar
Pyrimidine
Sources of atom:
Purine
Aspartic acid Glutamine Glycine CO2 N10-formyl-THF & N5,N10-methenyl-THF
Sources of atom:
Pyrimidine
Glutamine
Aspartic acid
CO2
5-PRPP synthesis Substrates:(2) Enzyme: Regulation: Pi? Purine?
5-PRPP synthesis Substrates: ATP & ribose 5 phosphate Enzyme: PRPP synthetase Regulation: Pi actives Purine inhibits
Committed step in purine synthesis
Enzyme:
Regulation:
AMP, GMP, IMP?
5 phosphoribosylamine synthesis
Enzyme: Glutamine PRPP amidotransferase
Regulators: AMP, GMP, IMP inhibits
Parent purine nucleotide
Inosine monophosphare
of steps for IMP synthesis
9
Base for IMP
Hypoxanthine
IMP to AMPS (adenylosuccinate)
Enzyme?
Requires?
IMP to AMPS (adenylosuccinate)
Enzyme? Adenylosuccinate synthase
Requires? GTP, Mg
IMP to AMP
Enzyme?
Adenylosuccinase
IMP to XMP
Enzyme?
Requires?
IMP to XMP
Enzyme? IMP dehydrogenase
Requires? NAD
XMP to GMP
Enzyme?
Requires?
XMP to GMP
Enzyme? Transamidinase
Requires? Glutamine –> Glutamate
De Novo Purine synthesis
PRPP 5-phosphoribosylamine IMP AMP GMP
Salvage pathways for purines: Irreversible enzymes (2)
APRT
HGPRT
CPS I vs II: Mitochondria Urea cycle Ammonia N-acetylglutamate activates
CPS I
CPS I vs II: Cytosol Pyrimidine Y-amide group of glutamine UTP inhibits ATP activates
CPS II
De Novo Pyrimidine Synthesis:
Regulated and rate limiting step: Enzyme: Regulator: UTP? ATP and PRPP
Synthesis of carbamoyl phosphate Enzyme: CPS II Regulator: UTP inhibits ATP and PRPP activates
De Novo Pyrimidine Synthesis:
Synthesis of orotic acid.
Enzyme:
Dihydroorotate dehydrogenase
Only step in de novo pyrimidine synthesis in mitochondria
Synthesis of orotic acid
Parent pyrimidine nucleotide
Orotidine monophosphate
De Novo Pyrimidine Synthesis:
OMP to UMP
Enzyme?
OMP Decarboxylase
De Novo Pyrimidine Synthesis:
UTP to CTP
Enzyme?
Reqt?
CTP synthase
Glutamine
De Novo Pyrimidine Synthesis:
UDP to dUDP
Enzyme?
Reqt?
Ribonucleotide reductase
NADPH
De Novo Pyrimidine Synthesis:
dUMP to TMP
Enzyme?
Reqt?
Thymidylate synthase
N5N10 methylene THF
Salvage-able pyrimidine:
Uridine & cytidine
Deoxycytidine
Thymidine
(Kinases for enzyme)
Deoxy form to oxy ribonucleoside?
Enxyme?
Reverse of ribonucleotide reductase?
Thioredoxin reductase
Enzyme?
Guanine to Guanylic Acid (GMP)
Hypoxanthine to Inosinic Acid (IMP)
HGPRT + PRPP
Enzyme?
Adenine to adenylic acid
APRT + PRPP
Enzymes:
Adenosine to Inosine
Adenosine deaminase (ADA)
Enzymes:
Hypoxanthine to Xanthine to Uric Acid
Xanthine oxidase
Products of pyrimidine degradation (2)
B-alanine. (–> acetyl coA)
B-aminoisobutyrate (–> succinyl coA)
Ex of PABA Analogs
Sulfonamides
Inhibit bacterial synthesis of folic acid
Sulfonamides
Ex of folic acid analogs
Methotrexate
TMP
Inhibit reduction of dihydrofolate to tetrahydrofolate, catalayzed by dihydrofolate reductase
Folic acid analogs
Methotrexate, TMP
X-linked recessive deficiency in HGPRT, causes a rise in intracellular PRPP and hyperuricemia
Lesch Nyhan Syndrome
Lesch Nyhan Syndrome triad
Hyperuricemia
Mental retardation
Self-mutilation
Leads to SCID (t and b lymphocytes affected)
High dATP –> inhibits ribonucleotide reductase and formation of deoxyribonucleotide
ADA deficiency
Metabolically conveted to 5-FdUMP which becomes permanently bound to thymidylate synthase
5-fluorouracil
Low activities of orotidine phosphate decarboxylase and orotate phosphoribosyltransferase
Orotic aciduria
Orotic aciduria manifestations? (3)
Abnormal growth
Megaloblastic anemia
Orotate in urine
