NUCLEOTIDES Flashcards
Structural analog of folate, selectively inhibits bacterial dihydrofolate reductase
Trimethoprim
Affected enzyme in Severe Combined Immunodeficiency Syndrome (SCID)
Adenosine Deaminase
Donors of atoms for PYRIMIDINE SYNTHESIS
- Glutamine (Q)
- Aspartate (D)
- CO2
- Enzyme Deficiency: HGPRT
- Clinical Presentation:
- ↑ PRPP and uric acid leads to gout
- Self-mutilation, mental retardation o X-linked disease
LESCH-NYHAN SYNDROME
Synthesis of Purine
o Accumulation of deoxyadenosine derivatives (↑ dATP) inhibits ribonucleotide reductase, leading to lack of DNA synthesis in immune cell precursors
o May present as severe combined immunodeficiency
o Absent thymus, no T-cell or B-cell production
(lymphocytopenia)
o Death before age 2 because of overwhelming infection
o Treat with bone marrow transplant, gene therapy
ADENOSINE DEAMINASE DEFICIENCY
How many rings does a pyrimidine have?
1
NucleoSides
BS: Base + Sugar only
rate limiting enzyme for PYRIMIDINE SYNTHESIS
Carbamoyl phosphate synthetase II
Donors of atoms of PURINE SYNTHESIS
- glutamine (Q)
- Aspartate (D)
- CO2
- Glycine (G)
- N10-formyltetrahydrofolate (Vit B9)
Nucleotides composition
BSP: Base + Sugar + Phosphate.
Reversible inhibitor of IMP dehydrogenase, depriving T and B lymphocytes of nucleic acids
Mycophenolate
Purine Salvage Pathway
- Converts dUMP to thymine
- Cofactor: N 5 ,N 10 -methylene tetrahydrofolate
- Inhibited by 5-fluorouracil
Thymidylate synthase
Pyrimidine synthesis
Metabolically converted to 5-FdUMP, which inhibits thymidylate synthase
5-fluorouracil
- Converts ribose 5-phoshate to its activated form, 5- phosphoribosyl-1-pyrophosphate (PRPP)
- Energy requirement: ATP → AMP
- PRPP is the donor of ribose 5-phosphate of nucleotides, whether they are synthesized de novo or through salvage patwhays
PRPP Synthase
- Inhibits xanthine oxidase
- Non-purine inhibitor of xanthine oxidase
Allopurinol
Febuxostat
inhibit dihydropteroate synthase
Sulfonamides
- Enzyme Deficiency: Glucose 6-phosphatase
- Clinical Presentation:
- ↑ ribose 5-phosphate leads to purine overproduction and hyperuricemia, and thus, gout
VON GIERKE DISEASE
*G6Phosphatase is needed in glycogenolysis/ gluconeogenesis in the liver for G6P to be converted to G (glucose). If that enzyme is missing, G6P will be shunted towards HMP (so dadami R5P na pwede pang produce ng nucleotides eventually madami dami need idegrade → hyperuricemia)
connects base to sugar
B-N-glycosidic bond
Affected enzyme in Lesch nyhan Syndrome
HGPRT
How many rings does a purine have?
2
bond that joins 2 nucleotides; condensation reaction; dehydration reaction
Phosphodiester bond
connects Phosphate to Sugar
Phosphoester Bond
parent molecule of purine synthesis
Inosine monophosphate (IMP)
what are the common substrates for Purine and pyrimidine synthesis?
• Glutamine
• Aspartate
• Carbon dioxide
Inhibits dihydrofolate reductase, which reduces the tetrahydrofolate supply for the synthesis of thymine
Methotrexate
- Enzyme Deficiency: Orotidine phosphate decarboxylase or orotate phosphoribosyl-transferase (UMP Synthase)
- Clinical Presentation:
- Impaired pyrimidine synthesis
- Poor growth
- Megaloblastic anemia
- Orotate in the urine
- Treat with uridine
OROTIC ACIDURIA
*These two enzymes belong to UMP synthase Note: if orotic aciduria + anemia = think UMP synthase deficiency! (pyrimidine pathway issue). But: if orotic aciduria + hyperAmmonemia and No anemia = think OTC deficiency! (urea cycle issue)
parent molecule of pyrimidine synthesis
Orotidine monophosphate (OMP)
- Enzyme Deficiency: Dihydropyrimidine dehydrogenase
- Clinical Presentation:
- Combined uraciluria-thyminuria
- Impaired formation of β-alanine and of β-aminoisobutyrate
β-HYDROXY-BUTYRIC ACIDURIA
Rate limiting enzyme for PURINE SYNTHESIS
PRPP glutamyl amidotransferase
