Podcast
Questions and Answers
What is a key characteristic of nucleotides?
What is a key characteristic of nucleotides?
Which of the following bases is specifically a purine?
Which of the following bases is specifically a purine?
What distinguishes thymine from uracil?
What distinguishes thymine from uracil?
What is produced when a pentose sugar is added to a nitrogenous base?
What is produced when a pentose sugar is added to a nitrogenous base?
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How is a nucleotide formed?
How is a nucleotide formed?
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Which of the following is a function of nucleotides in the cell?
Which of the following is a function of nucleotides in the cell?
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Which type of linkage is formed to produce a nucleoside?
Which type of linkage is formed to produce a nucleoside?
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What is the charge associated with DNA and RNA primarily due to?
What is the charge associated with DNA and RNA primarily due to?
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What is the first step in the de novo synthesis of purine nucleotides?
What is the first step in the de novo synthesis of purine nucleotides?
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Which pathway involves recycling free bases or nucleosides from nucleic acid breakdown?
Which pathway involves recycling free bases or nucleosides from nucleic acid breakdown?
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What role does ribonucleotide reductase (RR) play in nucleotide metabolism?
What role does ribonucleotide reductase (RR) play in nucleotide metabolism?
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Which of the following statements is true regarding the synthesis of inosine monophosphate (IMP)?
Which of the following statements is true regarding the synthesis of inosine monophosphate (IMP)?
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Which enzyme is considered the rate-limiting step in purine nucleotide biosynthesis?
Which enzyme is considered the rate-limiting step in purine nucleotide biosynthesis?
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What is one of the functions of adenylate kinase in nucleotide metabolism?
What is one of the functions of adenylate kinase in nucleotide metabolism?
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Which substance is structurally analogous to folic acid and used in cancer treatment?
Which substance is structurally analogous to folic acid and used in cancer treatment?
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Which two products are generated when ATP is converted during the synthesis of guanosine monophosphate (GMP)?
Which two products are generated when ATP is converted during the synthesis of guanosine monophosphate (GMP)?
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During which step of purine biosynthesis does glycine provide crucial components of the purine ring?
During which step of purine biosynthesis does glycine provide crucial components of the purine ring?
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What is the effect of PRPP concentration on the regulation of purine biosynthesis?
What is the effect of PRPP concentration on the regulation of purine biosynthesis?
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Study Notes
Nucleotide Synthesis
- Nucleotides are building blocks of nucleic acids (DNA & RNA)
- They're non-essential nutrients; the body synthesizes them
- Nucleotides form ATP (main energy source), coenzymes (NAD, NADP, FAD), and secondary messengers (cAMP, cGMP)
- Nucleotides regulate metabolic pathways
- Purine and pyrimidine bases can be synthesized de novo or via salvage pathways
- Nucleic acids are linear polymers for storing and transmitting genetic information
- Purine bases include adenine and guanine
- Pyrimidine bases include cytosine, uracil, and thymine
- Thymine and uracil differ; only thymine has a methyl group
- Some organisms have unusual bases in their DNA/RNA (e.g., viral DNA, tRNA) with modifications like methylation, acetylation, reduction, and glycosylation
Nucleosides
- A nucleoside is a base plus a pentose sugar (ribose/deoxyribose) linked via an N-glycosidic bond
- Ribose forms ribonucleosides; deoxyribose forms deoxyribonucleosides
Nucleotides
- Nucleotides are nucleosides with one or more phosphate groups
- Phosphate groups attach to the 5' carbon of the pentose sugar via ester bonds
- Phosphate groups give DNA and RNA a net negative charge
- ATP, ADP, and AMP are examples of nucleotides
- Nucleotides are named based on the base, sugar, and number of phosphates
Nucleotide Synthesis Pathways
- De novo synthesis: Nucleotides are synthesized from metabolic precursors (amino acids, ribose-5-phosphate, CO2, one-carbon units). Most synthesis occurs in the liver
- Salvage pathways: Nucleotides are synthesized by recycling free bases or nucleosides from nucleic acid breakdown; important for recycling RNA and DNA breakdown products
- Ribonucleotide to Deoxyribonucleotide conversion: Ribonucleotides are converted to deoxyribonucleotides at the diphosphate level via ribonucleotide reductase
Purine Biosynthesis
- Purine ring carbons and nitrogens come from various molecules
- The purine ring is built sequentially on a preformed ribose-5-phosphate
- All necessary enzymes are in the cytoplasm, primarily within the liver.
Purine Synthesis Steps
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Step 1: 5-Phosphoribosyl-1-pyrophosphate (PRPP) synthesis:
- Produced from ribose-5-phosphate via phosphoribosyl phosphate synthetase (PRPP synthetase)
- The committed step is usually not PRPP synthetase
- The synthesis of PRPP is regulated by concentrations of PRPP and the end products
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Step 2: 5’-phosphoribosylamine synthesis:
- Catalyzed by glutamine phosphoribosyl pyrophosphate amidotransferase (GPAT)
- This is the committed step in purine biosynthesis
- Highly regulated, with PRPP as an activator and GMP, AMP, and pathway end products as inhibitors
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Step 3 to 11: Other steps build on the 5'-phosphoribosylamine creating inosine monophosphate (IMP)
- The synthesis of the various parts of the purine ring including glycine, glutamine and carbon dioxide
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Adenine and guanine (AMP and GMP) are derived from IMP
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Control exists at several steps within the de novo pathway
Conversion of Nucleoside Monophosphates
- Nucleoside diphosphates (NDPs) and nucleoside triphosphates (NTPs) are formed from nucleoside monophosphates (NMPs) by specific nucleoside monophosphate kinases (e.g., adenylate kinase)
- ATP is the primary phosphate source.
- The balance of AMP, ADP, and ATP is maintained by adenylate kinase
Synthetic Inhibitors of Purine Synthesis
- Sulfonamides inhibit bacterial growth without affecting human cells
- Methotrexate inhibits nucleotide synthesis in rapidly dividing cells, including cancerous cells, by interfering with folic acid metabolism. It targets dihydrofolate reductase.
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Description
Explore the intricate world of nucleotides and nucleosides, the essential building blocks of DNA and RNA. This quiz covers their synthesis pathways, roles in energy transfer, and structural differences. Dive into the fascinating details of purine and pyrimidine bases, and their functions in genetic information storage.