NUCLEOTIDES

Question 1

Structural analog of folate, selectively inhibits bacterial dihydrofolate reductase

Answer 1

Trimethoprim

Question 2

Affected enzyme in Severe Combined Immunodeficiency Syndrome (SCID)

Answer 2

Adenosine Deaminase

Question 3

Donors of atoms for PYRIMIDINE SYNTHESIS

Answer 3

• Glutamine (Q)
• Aspartate (D)
• CO2

Question 4

• Enzyme Deficiency: HGPRT
• Clinical Presentation:
  
  • ↑ PRPP and uric acid leads to gout
  • Self-mutilation, mental retardation o X-linked disease

Answer 4

LESCH-NYHAN SYNDROME

Question 5

Synthesis of Purine

Answer 5

Question 7

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

Answer 7

ADENOSINE DEAMINASE DEFICIENCY

Question 8

How many rings does a pyrimidine have?

Answer 8

1

Question 9

NucleoSides

Answer 9

BS: Base + Sugar only

Question 10

rate limiting enzyme for PYRIMIDINE SYNTHESIS

Answer 10

Carbamoyl phosphate synthetase II

Question 11

Donors of atoms of PURINE SYNTHESIS

Answer 11

• glutamine (Q)
• Aspartate (D)
• CO2
• Glycine (G)
• N10-formyltetrahydrofolate (Vit B9)

Question 12

Nucleotides composition

Answer 12

BSP: Base + Sugar + Phosphate.

Question 13

Reversible inhibitor of IMP dehydrogenase, depriving T and B lymphocytes of nucleic acids

Answer 13

Mycophenolate

Question 14

Purine Salvage Pathway

Answer 14

Question 15

• Converts dUMP to thymine
• Cofactor: N 5 ,N 10 -methylene tetrahydrofolate
• Inhibited by 5-fluorouracil

Answer 15

Thymidylate synthase

Question 16

Pyrimidine synthesis

Answer 16

Question 17

Metabolically converted to 5-FdUMP, which inhibits thymidylate synthase

Answer 17

5-fluorouracil

Question 18

• 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

Answer 18

PRPP Synthase

Question 19

• Inhibits xanthine oxidase
• Non-purine inhibitor of xanthine oxidase

Answer 19

Allopurinol

Febuxostat

Question 20

inhibit dihydropteroate synthase

Answer 20

Sulfonamides

Question 21

• Enzyme Deficiency: Glucose 6-phosphatase
• Clinical Presentation:
  
  • ↑ ribose 5-phosphate leads to purine overproduction and hyperuricemia, and thus, gout

Answer 21

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)

Question 22

connects base to sugar

Answer 22

B-N-glycosidic bond

Question 24

Affected enzyme in Lesch nyhan Syndrome

Answer 24

HGPRT

Question 25

How many rings does a purine have?

Answer 25

2

Question 26

bond that joins 2 nucleotides; condensation reaction; dehydration reaction

Answer 26

Phosphodiester bond

Question 27

connects Phosphate to Sugar

Answer 27

Phosphoester Bond

Question 29

parent molecule of purine synthesis

Answer 29

Inosine monophosphate (IMP)

Question 30

what are the common substrates for Purine and pyrimidine synthesis?

Answer 30

**• Glutamine** **• Aspartate** **• Carbon dioxide**

Question 31

Inhibits **dihydrofolate reductase**, which reduces the tetrahydrofolate supply for the synthesis of thymine

Answer 31

Methotrexate

Question 32

* 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

Answer 32

**OROTIC ACIDURIA** ## Footnote \*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)

Question 33

parent molecule of pyrimidine synthesis

Answer 33

Orotidine monophosphate (OMP)

Question 34

* Enzyme Deficiency: **Dihydropyrimidine dehydrogenase** * Clinical Presentation: * Combined uraciluria-thyminuria * Impaired formation of β-alanine and of β-aminoisobutyrate

Answer 34

β-HYDROXY-BUTYRIC ACIDURIA

Question 35

Rate limiting enzyme for PURINE SYNTHESIS

Answer 35

PRPP glutamyl amidotransferase