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Questions and Answers
What is the primary biological role of nucleic acids?
What is the primary biological role of nucleic acids?
Which component is not a part of nucleotides?
Which component is not a part of nucleotides?
What are the two main types of nucleic acids mentioned?
What are the two main types of nucleic acids mentioned?
Which pathway is essential for the biosynthesis of purines?
Which pathway is essential for the biosynthesis of purines?
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What is the function of ribonucleotide reductase?
What is the function of ribonucleotide reductase?
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Which sugar lacks a 2'-OH group?
Which sugar lacks a 2'-OH group?
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What type of linkage is formed between a sugar and a nitrogenous base in a nucleoside?
What type of linkage is formed between a sugar and a nitrogenous base in a nucleoside?
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At which carbon does a purine bond to a sugar?
At which carbon does a purine bond to a sugar?
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How do nucleotides form?
How do nucleotides form?
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Which of the following correctly describes the numbering of sugars?
Which of the following correctly describes the numbering of sugars?
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What is the first step in the synthesis of Uridine Monophosphate (UMP)?
What is the first step in the synthesis of Uridine Monophosphate (UMP)?
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Which enzyme catalyzes the attachment of the base to the ribose ring in UMP synthesis?
Which enzyme catalyzes the attachment of the base to the ribose ring in UMP synthesis?
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Which nitrogen sources are involved in the synthesis of the pyrimidine ring?
Which nitrogen sources are involved in the synthesis of the pyrimidine ring?
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What is unique about OMP decarboxylase in the pyrimidine pathway?
What is unique about OMP decarboxylase in the pyrimidine pathway?
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How many ATP molecules are needed in the first step of UMP synthesis?
How many ATP molecules are needed in the first step of UMP synthesis?
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What is the role of binding energy between OMP and the active site?
What is the role of binding energy between OMP and the active site?
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Which enzyme catalyzes the transfer of phosphate to UMP to form UDP?
Which enzyme catalyzes the transfer of phosphate to UMP to form UDP?
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In animals, which enzyme is primarily regulated for pyrimidine synthesis?
In animals, which enzyme is primarily regulated for pyrimidine synthesis?
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What is a consequence of adenosine deaminase deficiency?
What is a consequence of adenosine deaminase deficiency?
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How are deoxyribonucleotides formed from ribonucleotides?
How are deoxyribonucleotides formed from ribonucleotides?
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What reaction is primarily regulated in bacteria for pyrimidine synthesis?
What reaction is primarily regulated in bacteria for pyrimidine synthesis?
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What happens to uracil when degraded in the liver?
What happens to uracil when degraded in the liver?
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What general process occurs for the degradation of CMP and UMP?
What general process occurs for the degradation of CMP and UMP?
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What type of RNA is formed from ribonucleotides?
What type of RNA is formed from ribonucleotides?
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Which of the following nucleotides contains Uracil?
Which of the following nucleotides contains Uracil?
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Which process uniquely involves ATP in purine nucleotide synthesis?
Which process uniquely involves ATP in purine nucleotide synthesis?
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What is the first purine derivative formed during de novo synthesis?
What is the first purine derivative formed during de novo synthesis?
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Which kind of nucleosides end in ‘-dine’?
Which kind of nucleosides end in ‘-dine’?
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What is the role of PRPP in nucleotide synthesis?
What is the role of PRPP in nucleotide synthesis?
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Which molecule acts as a central regulator in purine nucleotide biosynthesis?
Which molecule acts as a central regulator in purine nucleotide biosynthesis?
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What impact does increasing concentrations of GTP have on AMP production?
What impact does increasing concentrations of GTP have on AMP production?
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Which component is NOT involved in purine ring synthesis?
Which component is NOT involved in purine ring synthesis?
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Which statement about IMP conversion is false?
Which statement about IMP conversion is false?
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What is the end product of all purine degradation?
What is the end product of all purine degradation?
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Which nucleotides are formed from IMP during purine metabolism?
Which nucleotides are formed from IMP during purine metabolism?
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What is the role of hydrolyzing a phosphate from ATP during metabolic reactions?
What is the role of hydrolyzing a phosphate from ATP during metabolic reactions?
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What enzyme converts inosine to hypoxanthine during purine catabolism?
What enzyme converts inosine to hypoxanthine during purine catabolism?
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What is the final product of xanthine metabolism?
What is the final product of xanthine metabolism?
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Which enzyme catalyzes the conversion of adenosine to inosine?
Which enzyme catalyzes the conversion of adenosine to inosine?
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Which molecule is at the core of the purine degradation process?
Which molecule is at the core of the purine degradation process?
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What is the role of xanthine oxidase in purine metabolism?
What is the role of xanthine oxidase in purine metabolism?
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Which alternate pathway can uric acid take after its formation?
Which alternate pathway can uric acid take after its formation?
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How do humans primarily excrete uric acid?
How do humans primarily excrete uric acid?
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What substance is generated from aspartate at the expense of GTP in the purine nucleotide cycle?
What substance is generated from aspartate at the expense of GTP in the purine nucleotide cycle?
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Which enzyme is responsible for recycling ribose sugar during xanthine degradation?
Which enzyme is responsible for recycling ribose sugar during xanthine degradation?
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Which enzyme is responsible for the irreversible conversion of adenine to AMP?
Which enzyme is responsible for the irreversible conversion of adenine to AMP?
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Study Notes
Nucleic Acids - Chemistry, Function & Metabolism
- This lecture covers the structure, function, and associated disorders of nitrogenous bases, DNA, and RNA.
- The structure of nitrogenous bases are planar, aromatic, and heterocyclic.
- Bases are derived from purine or pyrimidine.
- The numbering of bases is "unprimed."
- The 5 carbon sugars are pentoses with numbering "primed."
Topic Outcomes
- Describe the structure, function, and biological role of nucleosides, nucleotides, and their analogues.
- Describe the structure, function, and types of nucleic acids (DNA, RNA).
- Explain purine and pyrimidine biosynthetic pathways and their regulation.
- Explain the role of ribonucleotide reductase.
- Describe the disorders associated with purine and pyrimidine metabolism.
Nitrogenous Bases
- Nitrogenous bases are categorized into purines (adenine, guanine) and pyrimidines (cytosine, thymine, uracil).
- Thymine is a 5-methyl uracil.
Sugars
- The 5-carbon sugars are known as pentoses.
- Ribose and 2'-deoxyribose are important sugars.
- The 2'-deoxyribose lacks a 2'-OH group.
Nucleosides
- Formed by linking sugars with a purine or pyrimidine base through N-glycosidic linkage.
- Purines bond to the C1' carbon of the sugar at their N9 atoms.
- Pyrimidines bond to the C1' carbon of the sugar at their N1 atoms.
Nucleotides
- Result from linking one or more phosphates to a nucleoside at the 5' end via esterification.
- Phosphates can be bonded to either C3 or C5 atoms of the sugar.
- Nucleotides can be mono-, di-, or triphosphates.
Nucleotides (Nucleic Acid Polymers)
- Monomers for nucleic acid polymers.
- Nucleoside Triphosphates are important energy carriers (ATP, GTP).
- Important components of coenzymes (FAD, NAD+, and Coenzyme A).
- RNA (ribonucleic acid) is a polymer of ribonucleotides.
- DNA (deoxyribonucleic acid) is a polymer of deoxyribonucleotides.
- Both deoxy- and ribonucleotides contain Adenine, Guanine, and Cytosine.
- Ribonucleotides contain Uracil.
- Deoxyribonucleotides contain Thymine.
Naming Conventions
- Purine nucleosides end in "-sine" (e.g., adenosine, guanosine).
- Pyrimidine nucleosides end in "-dine" (e.g., thymidine, cytidine, uridine).
- Nucleotides are named by adding "mono-," "di-," or "triphosphate" to the nucleoside name.
Nucleotide Metabolism
- Purine Ribonucleotides are formed de novo.
- Purine synthesis starts with the formation of Inosine Monophosphate (IMP).
- AMP and GMP are formed from IMP.
- Purine ring components come from various amino acids and bicarbonate.
Purine Nucleotide Synthesis
- ATP is involved in 6 steps of the synthesis process.
- PRPP is a precursor for Pyrimidine, Histidine, and Tryptophan synthesis.
- The C1 carbon notation changes from α to β in the second step.
- Hydrolyzing a phosphate from ATP is relatively easy, with a ∆G°' of -30.5 kJ/mol.
- The reaction is coupled to an exergonic reaction.
- Parts of ATP can be transferred to an acceptor molecule (P₁, PP₁, adenyl, or adenosinyl).
- ATP hydrolysis drives unfavorable reactions.
Purine Biosynthetic Pathway
- Channeling reactions organize pathway to increase rate and protect intermediates from degradation.
- Channeling is seen in reactions 3, 4, 6, 7, 8, and 10, 11 in animal cells.
IMP Conversion to AMP & GMP
- IMP is converted to AMP and GMP via different pathways.
Regulatory Control of Purine Nucleotide Biosynthesis
- GTP for AMP synthesis and ATP for GMP synthesis.
- PRPP is a central molecule in purine synthesis.
- ADP/GDP levels are important for negative feedback on Ribose Phosphate Pyrophosphokinase.
- Amidophosphoribosyl transferase is activated by PRPP.
Purine Catabolism
- Purine degradation leads to uric acid.
- Ingested nucleic acids are degraded to nucleotides, then to nucleosides, by pancreatic/intestinal enzymes.
- Nucleosides are absorbed directly and further degraded to various end products.
- Intracellular purine catabolism starts with the break down of nucleotides into nucleosides by 5'-nucleotidase.
- PNP (purine nucleoside phosphorylase) breaks down inosine into hypoxanthine.
Xanthine Degradation
- Ribose is recycled from xanthosine into ribose 1-phosphate.
- Hypoxanthine becomes xanthine via xanthine oxidase.
- Guanine is converted to Xanthine via Guanine Deaminase.
- Xanthine converts to uric acid via xanthine oxidase.
Xanthine Oxidase
- A homodimeric protein with electron transfer proteins.
- Contains FAD, Mo-pterin complex, and two 2Fe-2S clusters.
- Transfers electrons to O2, forming toxic H₂O₂.
- Toxic H₂O₂ is converted to water and O₂ by catalase.
The Purine Nucleotide Cycle
- Combining reactions involves the deamination of aspartate to fumarate.
Uric Acid Excretion
- Humans excrete uric acid into the urine as insoluble crystals.
- Birds, reptiles, and some insects excrete uric acid in paste form.
Purine Salvage
- Adenine phosphorybosyl transferase (APRT)
- Hypoxanthine-Guanine phosphoribosyl transferase (HGPRT)
- These are reversible reactions.
Gout
- Impaired excretion or overproduction of uric acid.
- Uric acid precipitates into joints, kidneys, and ureters, causing stones and gouty arthritis.
- Lead poisoning inhibits uric acid excretion, linked to the Fall of the Roman Empire.
- Xanthine oxidase inhibitors and allopurinol (a hypoxanthine analog) are used to treat gout.
Lesch-Nyhan Syndrome
- A defect in the HGPRT enzyme.
- Causes increased levels of hypoxanthine and guanine.
- Results in impaired uric acid breakdown.
- Neurological symptoms like spasticity, aggressiveness, and self-mutilation are also observed.
Purine Autism
- 25% of autistic patients may overproduce purines.
- Urine tests over 24 hours are performed to diagnose in adolescence.
Pyrimidine Ribonucleotide Synthesis
- Uridine Monophosphate (UMP) is synthesized first, then converted to CTP.
- Pyrimidine ring synthesis is completed first, then attached to ribose-5-phosphate.
- Aspartate, bicarbonate, and glutamine are sources for the pyrimidine ring.
Pyrimidine Synthesis
- 2 ATP required; one for transfer of phosphate.
- Formation of carbamoyl aspartate and dihydroorotate.
- Dihydroorotate dehydrogenase is an intra-mitochondrial enzyme.
UMP Synthesis Overview
- 2 ATPs needed (both used in the first step).
- Carbamoyl aspartate and dihydroorotate are formed via condensation reactions.
OMP Decarboxylase
- The final reaction in pyrimidine synthesis.
- Catalysis is proficient.
- High energy carbocation intermediate not required.
UTP and CTP Formation
- Nucleoside monophosphate kinase transfers P to UMP to form UDP.
- Nucleoside diphosphate kinase transfers P from ATP to UDP to form UTP.
- CTP is formed from UTP via CTP Synthetase driven by ATP hydrolysis.
- Glutamine provides amide nitrogen for C4.
Regulatory Control of Pyrimidine Synthesis
- Bacteria utilize different regulation of ATCase.
- Animals regulate carbamoyl phosphate synthetase II and activate it using ATP and PRPP.
- UMP/CMP inhibits OMP decarboxylase competitively.
- Purine synthesis is inhibited by ADP and GDP at the ribose phosphate pyrophosphokinase step, which regulates PRPP and pyrimidines.
Degradation of Pyrimidines
- Involves dephosphorylation, deamination, and glycosidic bond cleavage to degrade CMP and UMP to bases.
- Uracil is reduced in the liver into β-alanine.
- Converted to malonyl-CoA for fatty acid synthesis.
Deoxyribonucleotide Formation
- Purine/Pyrimidine Degradation pathways for ribonucleotides and deoxyribonucleotides are the same.
Adenosine Deaminase Deficiency
- In purine degradation, adenosine is converted to inosine by ADA.
- ADA deficiency causes SCID ("Severe Combined Immunodeficiency").
- ADA deficiency selectively kills lymphocytes (B-cells and T-cells).
- The active site is structurally perturbed in all known ADA mutants.
Adenosine Deaminase
- Enzyme catalyzing deamination of Adenosine to Inosine.
- α/β barrel domain structure; "TIM barrel" central structure.
- Active site at bottom of funnel-shaped pocket formed by loops.
- Found in glycolytic enzymes and proteins binding/transporting metabolites.
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Description
Test your knowledge on the fundamental roles and structures of nucleic acids. This quiz covers topics such as nucleotide components, biosynthesis pathways, and enzyme functions. Perfect for students studying biochemistry or molecular biology.