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Questions and Answers
Which of the following is NOT a function of nucleotides?
Which of the following is NOT a function of nucleotides?
Which nucleotide derivative is involved in lipid biosynthesis?
Which nucleotide derivative is involved in lipid biosynthesis?
Which of the following nucleotide(s) primarily act as second messengers in hormonally regulated events?
Which of the following nucleotide(s) primarily act as second messengers in hormonally regulated events?
What is a key role of ADP in metabolic regulation?
What is a key role of ADP in metabolic regulation?
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In a low pH environment, which nitrogen of adenine is most likely to be protonated?
In a low pH environment, which nitrogen of adenine is most likely to be protonated?
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What is true about the structures of purines and pyrimidines?
What is true about the structures of purines and pyrimidines?
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Which of the following is a medical application of synthetic purine and pyrimidine analogs?
Which of the following is a medical application of synthetic purine and pyrimidine analogs?
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What are the principal donors and acceptors of phosphoryl groups in metabolic processes?
What are the principal donors and acceptors of phosphoryl groups in metabolic processes?
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What type of bond is primarily involved in the formation of the 'backbone' of RNA and DNA?
What type of bond is primarily involved in the formation of the 'backbone' of RNA and DNA?
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Which of the following statements best describes the role of nucleoside triphosphates?
Which of the following statements best describes the role of nucleoside triphosphates?
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Why are synthetic, non-hydrolyzable analogs of nucleoside triphosphates useful research tools?
Why are synthetic, non-hydrolyzable analogs of nucleoside triphosphates useful research tools?
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How are the ends of a polynucleotide chain typically designated?
How are the ends of a polynucleotide chain typically designated?
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What is the primary difference between the phosphodiester bonds in RNA and DNA that affects their stability?
What is the primary difference between the phosphodiester bonds in RNA and DNA that affects their stability?
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Which of the following describes the bond between uracil and ribose in pseudouridine?
Which of the following describes the bond between uracil and ribose in pseudouridine?
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What is the main reason why the biological formation of dinucleotides doesn't occur by simple water elimination?
What is the main reason why the biological formation of dinucleotides doesn't occur by simple water elimination?
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What is the primary mechanism by which synthetic nucleotide analogs exert their cytotoxic effects in chemotherapy?
What is the primary mechanism by which synthetic nucleotide analogs exert their cytotoxic effects in chemotherapy?
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Given the representation pGpGpApTpCpA, what does the terminal 'p' indicate?
Given the representation pGpGpApTpCpA, what does the terminal 'p' indicate?
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What modification is required to produce TMP (thymidine monophosphate) from UMP in preformed tRNA?
What modification is required to produce TMP (thymidine monophosphate) from UMP in preformed tRNA?
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Which characteristic of purines and pyrimidines facilitates their close association in a double-stranded DNA?
Which characteristic of purines and pyrimidines facilitates their close association in a double-stranded DNA?
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What type of bond links the sugar to a purine or pyrimidine in nucleosides?
What type of bond links the sugar to a purine or pyrimidine in nucleosides?
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What distinguishes a mononucleotide from a nucleoside?
What distinguishes a mononucleotide from a nucleoside?
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Steric hindrance around the β-N-glycosidic bond leads to the existence of nucleosides and nucleotides in what forms?
Steric hindrance around the β-N-glycosidic bond leads to the existence of nucleosides and nucleotides in what forms?
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Which of the following is a modified purine or pyrimidine that occurs in nucleic acids?
Which of the following is a modified purine or pyrimidine that occurs in nucleic acids?
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At physiological pH, what is the net charge of nucleotides?
At physiological pH, what is the net charge of nucleotides?
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Why do nucleotides absorb ultraviolet light?
Why do nucleotides absorb ultraviolet light?
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Besides being precursors of nucleic acids, what is another significant role of ATP?
Besides being precursors of nucleic acids, what is another significant role of ATP?
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Which of the following functions as a second messenger in response to nitric oxide?
Which of the following functions as a second messenger in response to nitric oxide?
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What is the role of UDP-glucuronic acid?
What is the role of UDP-glucuronic acid?
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Which of these is an example of a plant-derived methylated heterocycle?
Which of these is an example of a plant-derived methylated heterocycle?
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What type of bonds are found in nucleotide triphosphates, and contribute to their high-group transfer potential?
What type of bonds are found in nucleotide triphosphates, and contribute to their high-group transfer potential?
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What is the approximate free energy change (ΔG°′) for the hydrolysis of the terminal (β or γ) phosphoryl group of a nucleoside triphosphate?
What is the approximate free energy change (ΔG°′) for the hydrolysis of the terminal (β or γ) phosphoryl group of a nucleoside triphosphate?
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What is the primary function of adenosine 3′-phosphate-5′-phosphosulfate?
What is the primary function of adenosine 3′-phosphate-5′-phosphosulfate?
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Which of the following is a function of GTP?
Which of the following is a function of GTP?
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Study Notes
Biomedical Importance of Nucleotides
- Nucleotides, including purines and pyrimidines, have diverse metabolic roles beyond nucleic acid precursors.
- They are involved in energy metabolism, protein synthesis, enzyme regulation, and signal transduction.
- Nucleotides linked to vitamins form coenzymes.
- Nucleotide triphosphates (ATP and ADP) are crucial for energy transfer in metabolic processes and oxidative phosphorylation.
- Nucleosides linked to sugars or lipids are key biosynthetic intermediates (e.g., UDP-glucose, UDP-galactose).
- Nucleotides participate in metabolic regulation through ATP-dependent phosphorylation of enzymes, allosteric regulation by ATP, ADP, AMP, and cGMP, and control of oxidative phosphorylation by ADP.
- Cyclic nucleotides (cAMP and cGMP) act as second messengers in hormonal responses.
- GTP and GDP are essential components in signal transduction pathways.
- Synthetic nucleotide analogs are used in cancer and AIDS chemotherapy and as immune response suppressants.
Chemistry of Purines, Pyrimidines, Nucleosides, and Nucleotides
- Purines and pyrimidines are heterocyclic aromatic compounds.
- Pyrimidine is larger than purine in structure but with longer name designation.
- Purines and pyrimidines with NH2 groups are weak bases (pKa values ~ 3-4). Protonation occurs at a ring nitrogen (N1 of adenine, N7 of guanine, N3 of cytosine).
- The planar structure of these molecules allows for stacking, which stabilizes double-stranded DNA.
- Keto–enol and amine–imine tautomerism of their oxo and amino groups exist, but physiological conditions favor the amino and oxo forms.
Nucleosides
- Nucleosides are derivatives of purines and pyrimidines with a sugar linked to a ring nitrogen.
- Ribonucleosides contain ribose, while deoxyribonucleosides contain 2-deoxy-d-ribose.
- The sugar is linked to the heterocycle via an α-N-glycosidic bond (typically to N1 of a pyrimidine or N9 of a purine).
Nucleotides
- Nucleotides are phosphorylated nucleosides.
- Mononucleotides have a phosphoryl group esterified to a hydroxyl group of the sugar.
- 3' and 5' nucleotides are nucleosides with a phosphoryl group on the 3'- or 5'-hydroxyl group, respectively.
- Most nucleotides are 5' nucleotides, thus the prime notation isn't always included in nomenclature.
- Additional phosphoryl groups form di- and triphosphates via acid anhydride bonds.
Conformers
- Steric hindrance from the heterocyclic ring prevents free rotation, thus exist as syn or anti conformers.
- Anti conformers are the predominant form in nature.
Modification of Polynucleotides
- Small quantities of modified purines and pyrimidines exist in DNA and RNA, e.g., methylated cytosine, hydroxymethylated cytosine, and methylated adenine/guanine.
- Modified heterocyclic bases, such as xanthine, hypoxanthine, and uric acid, are catabolism intermediates of adenine and guanine.
- Plant-derived methylated heterocycles (e.g., caffeine, theophylline, theobromine) are xanthine derivatives
Nucleotides as Polyfunctional Acids
- Primary and secondary phosphoryl groups have pKa values of ~1.0 and ~6.2 respectively.
- Purines and pyrimidines are typically neutral at physiological pH; hence, nucleotides bear a net negative charge.
Nucleotides and UV Light
- Conjugated double bonds in purine and pyrimidine derivatives absorb ultraviolet light.
- Common nucleotides absorb at around 260 nm at pH 7.0, allowing for concentration determination.
- UV light absorption by DNA can cause chemical modifications, leading to mutagenic effects.
Diverse Physiologic Functions of Nucleotides
- ATP is the primary biological energy transducer.
- cAMP is a second messenger.
- Intracellular concentrations differ significantly between ATP (1 mmol/L) and cAMP (1 nmol/L).
- Adenosine 3'-phosphate-5'-phosphosulfate is a sulfate donor for proteoglycans.
- S-adenosylmethionine is a methyl group donor.
- GTP functions as an allosteric regulator and energy source for protein synthesis.
- cGMP is a second messenger involved in smooth muscle relaxation (in response to nitric oxide).
- UDP-sugar derivatives mediate sugar epimerizations and participate in glycogen, glycoproteins, and proteoglycan biosynthesis/modification.
- UDP-glucuronic acid forms urinary glucuronide conjugates for bilirubin and many drugs (including aspirin).
- CDP-acylglycerol is an intermediate in lipid biosynthesis.
- Many coenzymes incorporate nucleotides or similar structures
Nucleotide Triphosphates and High-Group Transfer Potential
- Nucleotide triphosphates have high-group transfer potential due to acid anhydride bonds.
- Hydrolysis of terminal phosphoryl groups (β and γ) releases ~7 kcal/mol (-30kJ/mol).
- The high potential enables nucleotide triphosphates to act as group transfer reagents, especially for the γ-phosphoryl group, or in some cases, monophosphate transfer with simultaneous pyrophosphate release.
- This energy is coupled with other energy-requiring processes like covalent bond formation, e.g. nucleic acid synthesis.
Synthetic Nucleotide Analogs in Chemotherapy
- Synthetic analogs of purines, pyrimidines, nucleosides, and nucleotides, altered with halogens or additional nitrogen atoms, are used clinically (e.g. 5-fluorouracil, 3-deoxythymidine).
- Their toxic effects arise from interfering with nucleic acid synthesis mechanisms or incorporation, disrupting DNA base pairing.
- Allopurinol inhibits purine biosynthesis and xanthine oxidase activity.
- Cytarabine and azathioprine(converted to 6-mercaptopurine) are used in cancer chemotherapy and organ transplantation to suppress immune rejection, respectively
Non-Hydrolyzable Nucleotide Analogs
- Synthetic, non-hydrolyzable analogs of nucleotide triphosphates are research tools.
- They allow differentiation between phosphorylation effects and allosteric effects on regulatory enzymes.
DNA and RNA as Polynucleotides
- Polynucleotides are directional macromolecules.
- 3'→ 5' phosphodiester bonds connect the monomers.
- 5' and 3' ends are distinct ends for a polunucleotide.
- 5'-3' base sequence convention shows a 5'base to the left and a 3' base to the right.
- DNA is more stable than RNA due to differences in structure and hydroxyl groups.
- Post-translational modifications can form additional structures (e.g., pseudouridine, thymidine).
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Description
Explore the crucial roles of nucleotides in metabolism, energy transfer, and signaling pathways in this informative quiz. Understand their implications beyond just being nucleic acid precursors and their applications in therapies for diseases like cancer and AIDS.
