Nucleotide Flashcards by Lyssa Peralta

Purine

Guanine
Adenine

PUR-GA

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Pyrimidine

PyCUT

Cytosine
Uracil
Thymine

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Nucleoside link

B N glycosidic bond

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Purine vs pyrimidine

Ribose 5 phosphate first + ring

Purine

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Purine vs pyrimidine

Ring first plus sugar

Pyrimidine

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Sources of atom:

Purine

Aspartic acid
Glutamine
Glycine
CO2
N10-formyl-THF &amp; N5,N10-methenyl-THF

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Sources of atom:

Pyrimidine

Glutamine
Aspartic acid
CO2

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5-PRPP synthesis
Substrates:(2)
Enzyme:
Regulation: 
Pi?
Purine?

5-PRPP synthesis
Substrates: ATP &amp; ribose 5 phosphate
Enzyme: PRPP synthetase
Regulation: 
Pi actives
Purine inhibits

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Committed step in purine synthesis
Enzyme:
Regulation:
AMP, GMP, IMP?

5 phosphoribosylamine synthesis
Enzyme: Glutamine PRPP amidotransferase
Regulators: AMP, GMP, IMP inhibits

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Parent purine nucleotide

Inosine monophosphare

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of steps for IMP synthesis

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Base for IMP

Hypoxanthine

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IMP to AMPS (adenylosuccinate)
Enzyme?
Requires?

IMP to AMPS (adenylosuccinate)
Enzyme? Adenylosuccinate synthase
Requires? GTP, Mg

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IMP to AMP

Enzyme?

Adenylosuccinase

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IMP to XMP
Enzyme?
Requires?

IMP to XMP
Enzyme? IMP dehydrogenase
Requires? NAD

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XMP to GMP
Enzyme?
Requires?

XMP to GMP
Enzyme? Transamidinase
Requires? Glutamine –> Glutamate

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De Novo Purine synthesis

PRPP
5-phosphoribosylamine
IMP
AMP
GMP

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Salvage pathways for purines:
Irreversible enzymes (2)

APRT

HGPRT

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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