Nucleic Acids - Structure and Function

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Questions and Answers

What is the primary biological role of nucleic acids?

Cellular respiration

Protein synthesis

Information storage and transfer (correct)

Energy storage

Which type of nucleotide consists of a nitrogenous base, a sugar, and a phosphate group?

Nuclein

Nucleotide (correct)

Nucleoside

Nucleosome

Which of the following statements is true regarding purine biosynthesis?

Purine biosynthesis is not regulated.

Purines are synthesized only in the mitochondria.

Purines are exclusively synthesized from nucleotides.

Purine biosynthesis involves several enzymatic steps. (correct)

What is the function of ribonucleotide reductase in nucleotide metabolism?

Catalyzes the reduction of ribonucleotides to deoxyribonucleotides Signup and view all the answers

Which disorder is commonly associated with defects in purine metabolism?

Adenosine deaminase deficiency Signup and view all the answers

What is the primary cause of gout?

Impaired excretion or overproduction of uric acid Signup and view all the answers

What is the role of allopurinol in the treatment of gout?

It inhibits xanthine oxidase to decrease uric acid production Signup and view all the answers

What is a notable neurological symptom associated with Lesch-Nyhan Syndrome?

Self-mutilation Signup and view all the answers

What enzyme activity is affected in Lesch-Nyhan Syndrome?

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) Signup and view all the answers

What percentage of autistic patients is estimated to overproduce purines?

25% Signup and view all the answers

What type of sugar is found in nucleosides?

Pentoses (5-C sugars) Signup and view all the answers

Which nucleotide modification properly describes a triphosphate?

Contains three phosphates bonded to the nucleoside Signup and view all the answers

Which nitrogenous base is a purine?

Adenine Signup and view all the answers

What is the bonding position for purines with sugars?

C1’ carbon at the N9 atom Signup and view all the answers

What is unique about the structure of 2’-Deoxyribose compared to D-Ribose?

It lacks a 2’-OH group Signup and view all the answers

What is the first product synthesized in pyrimidine ribonucleotide synthesis?

Uridine Monophosphate (UMP) Signup and view all the answers

Which of the following substrates contributes to the pyrimidine ring during its synthesis?

Glutamine Signup and view all the answers

What role does OPRT play in the synthesis of UMP?

It catalyzes the attachment of the base to the ribose ring. Signup and view all the answers

Which statement accurately describes the enzyme OMP decarboxylase?

It is the most catalytically proficient enzyme in the pyrimidine pathway. Signup and view all the answers

What is the significance of channeling in pyrimidine synthesis?

It enhances the efficiency of substrate transport. Signup and view all the answers

What role does the binding energy between OMP and the active site play during the reaction?

It stabilizes the transition state. Signup and view all the answers

Which enzyme is responsible for catalyzing the transfer of Pi to UMP to form UDP?

Nucleoside monophosphate kinase Signup and view all the answers

How does regulation of pyrimidine synthesis differ between bacteria and animals?

Regulation sites are different in each organism. Signup and view all the answers

What is a consequence of adenosine deaminase (ADA) deficiency?

Severe combined immunodeficiency (SCID). Signup and view all the answers

Which molecule inhibits carbamoyl phosphate synthetase II in animals?

UDP Signup and view all the answers

What does deoxyribonucleotide formation primarily depend on?

The synthesis of ribonucleotides. Signup and view all the answers

What enzymatic activity is associated with the α/β barrel domain structure found in adenosine deaminase?

Deamination of adenine. Signup and view all the answers

What is the fate of uracil in the liver?

It is reduced to β-alanine. Signup and view all the answers

What distinguishes ribonucleotides from deoxyribonucleotides?

Ribonucleotides contain Uracil. Signup and view all the answers

Which type of nucleoside ends with the suffix '-dine'?

Thymidine Signup and view all the answers

How is ATP uniquely involved in the first step of purine nucleotide synthesis?

It participates in a group transfer. Signup and view all the answers

Which of the following is a precursor for both purine and pyrimidine synthesis?

PRPP Signup and view all the answers

What is the first purine derivative formed during purine nucleotide synthesis?

Inosine Monophosphate Signup and view all the answers

Which molecules exhibit negative feedback on Ribose Phosphate Pyrophosphokinase?

ATP and ADP Signup and view all the answers

What is the significance of channeling in the IMP synthesis pathway?

It organizes reactions to increase processing rate. Signup and view all the answers

What does the hydrolysis of PPi to 2Pi signify in purine synthesis?

It indicates a commitment in the synthesis pathway. Signup and view all the answers

Which molecules are involved in the reciprocal control of purine nucleotide biosynthesis?

ATP and GTP Signup and view all the answers

Which metabolite is a secondary product formed during purine catabolism?

Uric acid Signup and view all the answers

What happens to nucleotides during digestion in the intestine?

They are degraded to nucleosides. Signup and view all the answers

Which component of the purine ring is derived from bicarbonate ion?

C6 Signup and view all the answers

What does the term 'feedforward activation’ refer to in relation to purine biosynthesis?

Activation by increasing PRPP concentrations. Signup and view all the answers

Study Notes

Nucleic Acids - Chemistry, Function, & Metabolism

Learning Objectives: Discuss the structure of nitrogenous bases, the biological roles of DNA and RNA, and associated disorders.
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 and RNA).
- Explain purine and pyrimidine biosynthetic pathways and their regulation.
- Explain the role of ribonucleotide reductase.
- Describe disorders associated with purine and pyrimidine metabolism.

Nitrogenous Bases

Planar, aromatic, and heterocyclic structures
Derived from purine or pyrimidine
Base numbering is "unprimed"
Includes: Adenine (A), Guanine (G), Cytosine (C), Thymine (T), and Uracil (U).

Sugars

Pentoses (5-carbon sugars)
Numbering of sugars is "primed"
Includes D-Ribose and 2'-Deoxyribose
2'-Deoxyribose lacks a 2' hydroxyl group.

Nucleosides

Result from linking a sugar (ribose or deoxyribose) with a purine or pyrimidine base through an N-glycosidic linkage.
Purines bond to the 1' carbon at the N9 position.
Pyrimidines bond to the 1' carbon at the N1 position.

Nucleotides

Result from linking one or more phosphates to a nucleoside through esterification at the 5' end of the sugar.
Phosphates can be bonded to either C3 or C5 atoms.
Forms mono-, di-, or triphosphates.
Examples: Adenosine Monophosphate (AMP), 2'-Deoxythymidine Monophosphate.

Nucleotides (continued)

Monomers for nucleic acid polymers
Important energy carriers (ATP, GTP)
Components of coenzymes (FAD, NAD+, Coenzyme A)
RNA is a polymer of ribonucleotides.
DNA is a polymer of deoxyribonucleotides.
Both DNA and RNA contain Adenine, Guanine, and Cytosine.
Ribonucleotides contain Uracil.
Deoxyribonucleotides contain Thymine.

Naming Conventions

Nucleosides: Purine nucleosides end in "-sine" (e.g., adenosine, guanosine); Pyrimidine nucleosides end in "-dine" (e.g., thymidine, cytidine, uridine).
Nucleotides: Add "mono-," "di-," or "triphosphate" to the nucleoside name (e.g., adenosine monophosphate, cytidine triphosphate).

Nucleotide Metabolism

Purine Ribonucleotides: Formed de novo; first purine derivative is Inosine Monophosphate (IMP).
Purine ring components are derived from aspartate, glutamine, glycine, and formate.
AMP and GMP are formed from IMP.

Purine Nucleotides

Purine ring components are derived from aspartate, formate, glutamine, and glycine.
Uric acid is a final breakdown product.

Purine Nucleotide Synthesis

ATP plays a key role
PRPP is a precursor to pyrimidine, histidine, and tryptophan synthesis
Channeling reactions help increase overall rate.

IMP Conversion to AMP and GMP

Different pathways for AMP and GMP synthesis from IMP.
Requires different enzymes and energy sources

Regulatory Control of Purine Nucleotide Biosynthesis

GTP plays a role in AMP synthesis, and ATP plays a role in GMP synthesis (reciprocal control).
PRPP is a central molecule in the pathway, and its levels affect the entire process.
Feedback inhibition by nucleotides (ADP, GDP, AMP, GMP, and others)
Some enzymes have allosteric sites on multiple nucleotides, for regulation

Purine Catabolism and Salvage

Ingested nucleic acids are degraded to nucleotides by pancreatic enzymes and intestinal enzymes in the intestine.
Nucleosides are then absorbed and further degraded.
Uric acid is the primary end product in humans.
Salvage pathways allow the organism to reuse bases and nucleotides.

Intracellular Purine Catabolism

Nucleotides are broken down to nucleosides by 5'-nucleotidase.
Purine nucleoside phosphorylase (PNP) and other enzymes convert nucleosides into bases like hypoxanthine, xanthine, and guanine.
Xanthine is oxidized to uric acid by xanthine oxidase.

Xanthine Oxidase

A homodimeric protein that contains electron transfer proteins, FAD, and a Mo-pterin complex.
Catalyzes the conversion of xanthine to uric acid.
Transfers electrons to oxygen; generates hydrogen peroxide (H₂O₂), which is toxic.
H₂O₂ is further converted to oxygen and water by catalase.
The Purine Nucleotide Cycle*
A cycle involves the conversion of AMP to IMP and back.
Aspartate is deaminated to fumarate during the cycle.

Uric Acid Excretion

Humans excrete uric acid crystals in urine.
Birds, reptiles, and some insects excrete uric acid as insoluble crystals (paste form).
High concentrations of uric acid in humans or animals may cause kidney stones

Purine Salvage

Adenine phosphoribosyl transferase (APRT) and hypoxanthine-guanine phosphoribosyl transferase (HGPRT) catalyze the addition of a ribose-phosphate to free bases..
This allows the reuse of purine bases.

Gout

Gout arises from impaired excretion or overproduction of uric acid.
Uric acid crystals can accumulate in joints, causing inflammation.

Allopurinol

Allopurinol is a xanthine oxidase inhibitor that is used to treat gout.
It inhibits uric acid formation.

Lesch-Nyhan Syndrome

A genetic disorder caused by deficient HGPRT.
Leads to increased levels of uric acid and neurological symptoms such as spasticity, aggression, and self-harm.

Purine Autism

High levels of purine production may be present in 25% of the autistic population.

Pyrimidine Ribonucleotide Synthesis

Uridine monophosphate (UMP) is synthesized first.
CTP is synthesized from UMP.
Pyrimidine ring is first synthesized; then attached to ribose-5-phosphate.

Pyrimidine Synthesis

2 ATP and bicarbonate needed in first step.
Condensation Reactions between Carbamoyl Phosphate and Aspartate; forming Dihydroorotate;
Final Reaction is catalyzed by OMP Decarboxylase; releasing CO2

UMP Synthesis Overview

2 ATPs are required, one is used in the initial step.
Two reactions form carbamoyl aspartate and dihydroorotate.
Dehydrogenase converts the reaction to orotate to orotate monophosphate.
Ribose attaches to the orotate by Phosphoribosyl transferase forming orotidylate
This molecule is then converted to UMP.

OMP Decarboxylase

This enzyme is extremely efficient, with high catalytic proficiency.

UTP and CTP Synthesis

Nucleoside monophosphate kinases convert UMP to UDP and then UTP.
CTP is generated from UTP.
Glutamine contributes to the amide nitrogen for the process.

Regulatory Control of Pyrimidine Synthesis

Bacteria and animals differ in their regulatory mechanisms.
UDP and UTP inhibit carbamoyl phosphate synthetase II, one of the rate-limiting enzymes.
ATP and PRPP can activate the enzyme, promoting pyrimidine synthesis.

Degradation of Pyrimidines

Pyrimidines are degraded similarly to purines.
Steps are: dephosphorylation, deamination, and glycosidic bond cleavage.
Uracil is converted to ẞ-alanine, which can be further metabolized
All these steps result in the excretion of the final products into the urine, in the form of soluble crystals.

Deoxyribonucleotide Formation

Deoxyribonucleotides are synthesized from corresponding ribonucleotides.
Biosynthetic pathways are only for ribonucleotide production.

Adenosine Deaminase Deficiency

Adenosine deaminase (ADA) is essential in purine degradation.
ADA deficiency (or mutations), results in severe combined immunodeficiency (SCID), a severe immunodeficiency.
ADA deficiency leads to the build-up of toxic compounds, and the buildup of compounds blocks the normal function of the immune system, preventing lymphocytes (white blood cells that are essential for the immune response) to function at an optimal level.
All known ADA mutations affect the active site of this enzyme.

Adenosine Deaminase

The α/β barrel domain structure determines the enzyme's function.
The "TIM barrel" is a central barrel structure with 8 twisted parallel beta-strands connected by beta-turns and alpha-helices.
The active site in the bottom of the funnel-shaped pocket is formed by loops in the protein.
Adenosine deaminase is found in glycolytic enzymes; present in proteins that bind and transport metabolites.

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Description

Explore the essential roles of nucleic acids in biology, including the structure and function of DNA and RNA. This quiz covers nitrogenous bases, biosynthetic pathways, and related metabolic disorders, enhancing your understanding of nucleic acid metabolism.