Term
| Identify which bases are found in DNA and which are found in RNA |
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Definition
DNA-Adenine, Guanine, Thymine, Cytosine
RNA-Adenine, Guanine, Uracil, Cytosine |
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Term
| Explain the differences in the structures of bases, nucleosides, and nucleotides |
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Definition
-bases:
purines- 1 five member ring fused with a 6 member ring
pyrimidines- 1 six member ring
-nucleosides- base + ribose
-nucleotides- base +ribose-phosphate |
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Term
| Explain the difference between the structures of ribose and deoxyribose |
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Definition
| deoxyribose lacks an OH group that ribose has at C2 |
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Term
| Indicate the biosynthetic source of each atom in the purine ring |
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Definition
Aspartate (amine)- N at position 1
N10-Formal-FH4- C at 2
Glutamine (amide)- N at 3 and N at 9
Glycine- C 4, 5, ,7
CO2- C6
N10-Formyl-FH4 - C8 |
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Term
| Describe the mechanism of action of the anti-tumor agent, 6-mercaptopurine |
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Definition
1. 6-Mercaptopurine is converted to a nucleotide
2. The nucleotide inhibits purine biosynthesis at
steps 2, 12a, 12b, and 13a
3. Acute lymphocytic leukemia (ALL) |
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Term
| Indicate the biosynthetic source of each atom in the pyrimidine ring |
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Definition
Glutamine- N at 3
CO2- N at 2
Aspartate- N at 1; C at 4, 5, 6 |
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Term
| Describe the regulated step in pyrimidine biosynthesis |
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Definition
The regulated step is catalyzed by carbamoyl phosphate synthetase II
(Glutamate + CO2 + ATP -> carbamoyl phosphate + aspartic acid) |
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Term
| Indicate whether the pyrimidine ring is synthesized first and then attached to ribose, or whether the pyrimidine ring is synthesized on top of ribose |
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Definition
| the pyrimidine ring is synthesized first and then attached to ribose |
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Term
| Name the pyrimidine nucleoside that is biosynthesized first and becomes a precursor for the synthesis of the other pyrimidine nucleotides |
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Definition
| UMP (uracil mono phosphate ) |
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Term
| Indicate which metabolic pathway is blocked by the rheumatoid arthritis drug, leflunomide |
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Definition
| it inhibits the enzyme, dihydroorotate dehydrogenase; pyrimidine synthesis is the pathway that is blocked |
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Term
| Suggest why an inhibitor of purine biosynthesis might be useful in slowing tumor growth |
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Definition
| tumors are very dependent on purine biosynthetic pathway to produce purine nucleotides for DNA and RNA synthesis, a drug that could inhibit this would be more toxic to tumor cells than to most normal cells (normal cells usually recycle purine bases) |
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Term
| Indicate whether the purine ring is synthesized first and then attached to ribose, or whether the purine ring is synthesized on top of ribose |
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Definition
| purine ring is synthesized ON top of ribose |
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Term
| Indicate the first two enzymatic steps in purine biosynthesis starting with ribose-5-phosphate. Name the products and indicate the source of ribose-5-phosphate. Identify the enzyme that catalyzes the committed and major regulated step |
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Definition
| Ribose-5-phosphate comes from the pentose-phosphate pathway. 1. The first step is the activation of ribose-5-phosphate to give PRPP, with pyrophosphate coming from ATP 2. The second step is the formation of 5-phosporibosylamine with the amino group coming from glutamine . This is catalyzed by glutamine PRPP amidotransferase ****committed step and major regulated step |
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Term
| Indicate which nucleotide stands at the branch point leading to the synthesis of AMP and GMP |
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Definition
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Term
| Describe the synthesis of dTMP from dUMP |
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Definition
| -this requires thymidylate synthase; N5,N5-methylene tetrahydrofolate is converted to dihydrofolate (methyl given to dTMP) |
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Term
| Describe how 5'-fluorouracil acts as an antitumor agent |
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Definition
| -is converted to f-dUMP -acts as a pseudosubstrate -forms a covalent bond with thymidylate synthase and inhibits it (so it inhibits dUMP to dTMP) |
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Term
| Describe how methotrexate acts as an antitumor agent |
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Definition
| -Methotrexate causes an intracellular tetrahydrofolate deficiency by inhibiting dihydrofolate reductase which is an enzyme that converts the toxic dihydrofolate (produced from dUMP to dTMP reaction) into tetrahydrofolate -acts as a competitive inhibitor |
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Term
| Name the enzyme responsible for the synthesis of the deoxyribonucleotides and indicate the substrates for this enzyme |
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Definition
| - enzyme: Ribonucleotide reductase - substrates: ribonucleoside 5'-diphosphates (ADP, GDP,CDP, or UDP) |
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Term
| Which hydroxyl group is removed from the ribose in this process |
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Definition
| 2' hydroxyl group is replaced with a hydrogen atom by ribonucleotide reductase in the formation of deoxyribose |
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Term
| Describe the mechanism of the antitumor effect of hydroxyurea (small group problem) |
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Definition
| - inhibits ribonucleotide reductase; this specifically affects DNA synthesis |
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Term
| Describe how deoxyribonucleotide biosynthesis is regulated during the cell cycle |
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Definition
| -DNA synthesis occurs in the S phase - In late G1 and early S phase, enzymes involved in purine/pyrimidine biosynthesis are increased (such as ribonucleotide reductase and thymidylate synthase) -concentrations of deoxyribonucleotides are increased in S phase |
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Term
| Name the classes of enzymes involved in degradation of DNA and RNA. |
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Definition
| nucleases, nucleotidases,and nucleoside phosphorylases |
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Term
| Indicate which bases are formed by degradation of DNA and RNA |
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Definition
pyrimidine bases: uracil and thymine
purine bases: guanine and hypoxanthine |
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Term
| Describe the enzymatic reaction involved in salvaging hypoxanthine and guanine |
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Definition
| most free purine bases are reutilized instead of degraded; HGPRTase is the enzyme that converts guanine and hypoxanthine, each added to PRPP, into GMP and IMP, respectively. |
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Term
| Indicate the genetic deficiency in Lesch-Nyhan syndrome |
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Definition
| deficiency in HGPRTase (can't reutilize hypoxanthine and guanine to make IMP and GMP, respectively) |
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Term
| Indicate the final product of purine degradation in humans |
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Definition
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Term
| Name the enzyme that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid |
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Definition
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Term
| Indicate the forms of uric acid present in the blood and urine |
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Definition
blood- urate
urine- uric acid |
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Term
| Describe the consequences of overproduction or underexcretion of uric acid |
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Definition
gout
-hyperuriemia
-hyperuricosuria |
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Term
| Describe the mechanism by which allopurinol relieves the symptoms of gout |
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Definition
| -inhibitor of xanthine oxidase -reduces urate and uric acid in the blood and urine, and also reduces the size of tophi and renal uric acid stones |
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