Nucleotide Synthesis and Thymidylate Synthase
42 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the role of thymidylate synthase in nucleotide synthesis?

  • It converts dUMP to dTMP. (correct)
  • It synthesizes orotic acid.
  • It phosphorylates uridine.
  • It inhibits ribonucleotide reduction.

Orotic aciduria results from high activities of orotate phosphoribosyl transferase and orotidylate decarboxylase.

False (B)

What nitrogen donor is used in the synthesis of cytidine from uridine?

glutamine

5-Fluorouracil is a thymine analogue and irreversibly inhibits thymidylate synthase by binding to it and causing _______.

<p>covalent modification</p> Signup and view all the answers

Match the following inhibitors with their effects:

<p>5-Fluorouracil = Irreversible inhibitor of thymidylate synthase Methotrexate = Inhibits reduction of Dihydrofolate to Tetrahydrofolate Orotate = Causes abnormal growth when accumulated CTP synthase = Converts UTP to CTP</p> Signup and view all the answers

What are the building units of DNA and RNA?

<p>Nucleotides (C)</p> Signup and view all the answers

ATP and GTP are both sources of energy in biological systems.

<p>True (A)</p> Signup and view all the answers

What is the role of cAMP and cGMP in the cell?

<p>They serve as second messengers in signal transduction pathways.</p> Signup and view all the answers

Nucleotides are essential for the _________ of the genome.

<p>replication</p> Signup and view all the answers

Match the following components of nucleotides with their correct descriptions:

<p>Nitrogenous Base = Purines or pyrimidines Pentose Sugar = Ribose or deoxyribose Phosphate = 1P, 2P, or 3P</p> Signup and view all the answers

Which of the following is NOT a function of nucleotides?

<p>Directly coding for proteins (D)</p> Signup and view all the answers

Hyperuricemia is a condition related to the degradation of pyrimidines.

<p>False (B)</p> Signup and view all the answers

Name one clinical manifestation of Lesch-Nyhan syndrome.

<p>Gout</p> Signup and view all the answers

What percentage of nucleotide synthesis can come from salvage pathways?

<p>90% (B)</p> Signup and view all the answers

The pyrimidine ring is completely broken down into CO2 and NH4+ during nucleotide biosynthesis.

<p>True (A)</p> Signup and view all the answers

What is urate, and why might it contribute to increased lifespan in humans?

<p>Urate is a degradation product of purine bases and acts as a powerful antioxidant, which may aid in increasing lifespan.</p> Signup and view all the answers

Deoxyribonucleotides are synthesized from ribonucleotides by __________.

<p>reduction</p> Signup and view all the answers

Match the following disorders to their causes:

<p>Gout = Precipitation of urate crystals Lesch-Nyhan syndrome = Inactive salvage pathway enzyme High urate levels = Frequent disease occurrence Spasticity = Defect in urate clearance</p> Signup and view all the answers

What is the main precursor used in the biosynthesis of nucleotides?

<p>Phosphoribosyl pyrophosphate (PRPP) (D)</p> Signup and view all the answers

The salvage pathway requires more energy compared to the de novo pathway.

<p>False (B)</p> Signup and view all the answers

Which of the following purine nucleotides is formed from the addition of aspartate?

<p>AMP (C)</p> Signup and view all the answers

What is the first step in pyrimidine biosynthesis?

<p>Synthesis of carbamoyl phosphate</p> Signup and view all the answers

The salvage pathway accounts for 90% of purine nucleotides formation.

<p>True (A)</p> Signup and view all the answers

The enzyme used in the first step of pyrimidine biosynthesis is ________.

<p>CPS II</p> Signup and view all the answers

What regulates the overall rate of purine biosynthesis?

<p>Feedback inhibition</p> Signup and view all the answers

Adenine phosphoribosyltransferase catalyzes the formation of __________.

<p>adenylate</p> Signup and view all the answers

Match the following pathways with their descriptions:

<p>De Novo Pathway = Synthesis from simpler materials using energy Salvage Pathway = Synthesis from preformed bases with minimal energy CPS II = Enzyme for carbamoyl phosphate synthesis Transcarbomylase = Catalyzes ring closure in pyrimidine biosynthesis</p> Signup and view all the answers

Match the following terms with their descriptions:

<p>IMP = Precursor of AMP and GMP HGPRT = Enzyme that catalyzes the formation of guanylate Adenylosuccinate = Intermediate in AMP synthesis Fumarate = Released during AMP formation process</p> Signup and view all the answers

Which of the following statements about nucleotide biosynthesis is correct?

<p>Salvage pathways can account for up to 90% of nucleotide synthesis. (C)</p> Signup and view all the answers

The reaction catalyzed by transcarbomylase involves the conversion of carbamoyl phosphate and aspartate.

<p>True (A)</p> Signup and view all the answers

Which compound is a precursor of GMP?

<p>Inosine Monophosphate (C)</p> Signup and view all the answers

What is the main component that activates the reaction in the biosynthesis of nucleotides?

<p>Phosphoribosyl pyrophosphate (PRPP)</p> Signup and view all the answers

Hydrolysis of glutamine contributes an amino group to the synthesis of GMP.

<p>True (A)</p> Signup and view all the answers

Nucleotide biosynthesis is controlled by __________ regulation.

<p>feedback</p> Signup and view all the answers

What is the final product of purine degradation in humans?

<p>Urate (A)</p> Signup and view all the answers

Urate has no antioxidant properties in humans.

<p>False (B)</p> Signup and view all the answers

What illness is characterized by self-destructive behavior and is linked to a deficiency in HGPRT?

<p>Lesch-Nyhan syndrome</p> Signup and view all the answers

Elevated levels of urate can lead to _____ in the kidneys.

<p>kidney stones</p> Signup and view all the answers

Match the following diseases or conditions with their associated enzymes or effects:

<p>Gout = Xanthine oxidase inhibitor Lesch-Nyhan syndrome = HGPRT deficiency ADA Deficiency = Adenosine deaminase deficiency Allopurinol = Reduces uric acid levels</p> Signup and view all the answers

What medication is used to treat gout by inhibiting xanthine oxidase?

<p>Allopurinol (A)</p> Signup and view all the answers

High levels of urate are beneficial as they can lead to a longer lifespan.

<p>True (A)</p> Signup and view all the answers

What is the primary consequence of the mutation of nucleotide biosynthetic enzymes?

<p>Accumulation of intermediates</p> Signup and view all the answers

Flashcards

Nucleotides

The basic building blocks of DNA and RNA, essential for genetic replication, transcription, and various cellular processes.

Nucleotide Structure

Organic molecules containing a nitrogenous base, a pentose sugar (ribose or deoxyribose), and one or more phosphate groups.

Purines

Double-ringed nitrogenous bases found in nucleotides, including adenine (A) and guanine (G).

Pyrimidines

Single-ringed nitrogenous bases found in nucleotides, including cytosine (C), thymine (T), and uracil (U).

Signup and view all the flashcards

Nucleotide Biosynthesis

The process by which cells synthesize purines and pyrimidines, which are essential components of nucleotides.

Signup and view all the flashcards

Feedback Inhibition

A process that regulates nucleotide biosynthesis, where the product of a pathway inhibits an earlier step in the same pathway.

Signup and view all the flashcards

Purine Degradation Disorders

Disorders caused by abnormalities in the metabolism of purines, leading to the accumulation of uric acid in the body.

Signup and view all the flashcards

Lesch-Nyhan Syndrome

A rare genetic disorder characterized by hyperuricemia, self-mutilation, and developmental delays.

Signup and view all the flashcards

Orotic Aciduria

A genetic disorder caused by deficiencies in orotate phosphoribosyltransferase and orotidylate decarboxylase, leading to abnormal growth, megaloblastic anemia, and excessive orotate excretion in urine.

Signup and view all the flashcards

Deoxyribonucleotide Synthesis

The process of converting ribonucleotides (RNA building blocks) into deoxyribonucleotides (DNA building blocks).

Signup and view all the flashcards

Thymidylate Synthase

The enzyme responsible for catalyzing the conversion of dUMP to dTMP, a critical step in DNA synthesis.

Signup and view all the flashcards

5-Fluorouracil (5-FU)

A potent inhibitor of thymidylate synthase. It acts as a thymine analogue and irreversibly binds to the enzyme, preventing dTMP synthesis.

Signup and view all the flashcards

Methotrexate (MTX)

An inhibitor of dihydrofolate reductase, an enzyme essential for the production of tetrahydrofolate (THF), a coenzyme vital for thymidylate synthase.

Signup and view all the flashcards

De Novo nucleotide biosynthesis

The process of building nucleotides from simpler molecules, using energy and multiple enzymes.

Signup and view all the flashcards

Salvage pathway for nucleotide synthesis

The process of reusing pre-existing bases to create nucleotides, saving energy and resources.

Signup and view all the flashcards

Phosphoribosyl pyrophosphate (PRPP)

A molecule crucial for nucleotide synthesis, derived from ribose-5-phosphate and ATP.

Signup and view all the flashcards

Carbamoyl phosphate synthesis

The first step in pyrimidine biosynthesis, forming carbamoyl phosphate.

Signup and view all the flashcards

CPS II (Carbamoyl phosphate synthetase II)

This enzyme forms carbamoyl phosphate for pyrimidine synthesis using glutamine as the nitrogen source. It works in the cytosol.

Signup and view all the flashcards

Aspartate & carbamoyl phosphate reaction

The second step in pyrimidine biosynthesis, where carbamoyl phosphate combines with aspartate, followed by ring closure and dehydration to form orotate.

Signup and view all the flashcards

Transcarbomylase

This enzyme catalyzes the reaction between carbamoyl phosphate and aspartate in pyrimidine biosynthesis.

Signup and view all the flashcards

Orotate

A compound formed in pyrimidine biosynthesis, precursor to the pyrimidine base uracil.

Signup and view all the flashcards

Salvage Pathway

Nucleotide synthesis pathways use pre-existing nitrogenous bases from breakdown of other nucleotides or food, which are then attached to activated ribose (PRPP). This process is more energy-efficient than de novo synthesis.

Signup and view all the flashcards

De Novo Biosynthesis

De novo synthesis assembles nucleotides from simple molecules like activated ribose (PRPP), amino acids, and 1 to 4 carbon units.

Signup and view all the flashcards

Purine Degradation

Purine degradation ultimately leads to the formation of uric acid, which is excreted in urine.

Signup and view all the flashcards

Gout

A condition characterized by high levels of uric acid in the blood, often leading to painful inflammation of joints.

Signup and view all the flashcards

Xanthine oxidase

An enzyme that breaks down purines, ultimately producing uric acid.

Signup and view all the flashcards

Allopurinol

A drug commonly used to treat gout by inhibiting xanthine oxidase, reducing uric acid levels.

Signup and view all the flashcards

Inosine Monophosphate (IMP)

Inosine monophosphate (IMP) is a key intermediate in purine biosynthesis. It can be converted into either AMP (adenosine monophosphate) or GMP (guanosine monophosphate) through different enzymatic reactions, forming the building blocks for DNA and RNA.

Signup and view all the flashcards

Pyrimidine Catabolism

The breakdown of pyrimidine bases, resulting in complete degradation to carbon dioxide and ammonia.

Signup and view all the flashcards

Feedback Inhibition in Purine Biosynthesis

Feedback inhibition is a regulatory mechanism where the product of a metabolic pathway inhibits an enzyme earlier in the same pathway, preventing overproduction of the products. This is important for fine-tuning purine nucleotide synthesis.

Signup and view all the flashcards

Dietary nucleic acid degradation

The breakdown of nucleic acids from food in the small intestine, a key source of nucleotides for the body.

Signup and view all the flashcards

Adenylate Succinase

Adenylate succinase is an enzyme that catalyzes the removal of fumarate from adenylosuccinate, generating AMP. This step is essential for the synthesis of adenine nucleotides.

Signup and view all the flashcards

GMP Synthetase

GMP synthetase is the enzyme that converts IMP into GMP. It uses glutamine as a source of nitrogen and involves a series of reactions involving oxidation and reduction.

Signup and view all the flashcards

Adenine Phosphoribosyltransferase (APRT)

Adenine phosphoribosyltransferase (APRT) is an enzyme that catalyzes the attachment of a phosphoribosyl group to adenine to produce AMP, a key step in the salvage pathway.

Signup and view all the flashcards

Hypoxanthine-guanine Phosphoribosyl Transferase (HGPRT)

Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) is an enzyme involved in the salvage pathway that converts hypoxanthine or guanine into their respective nucleotides, IMP or GMP.

Signup and view all the flashcards

Importance of the Salvage Pathway

The salvage pathway is responsible for the synthesis of about 90% of purine nucleotides, highlighting its importance in providing cells with the building blocks needed for DNA, RNA, and other vital molecules.

Signup and view all the flashcards

Study Notes

PHBC 522 - Biochemistry I, Winter 2024, Lecture 7 - Nucleotide Metabolism

  • Learning Outcomes: Students should be able to draw purine and pyrimidine structures, identify purine and pyrimidine biosynthesis pathways, describe nucleotide biosynthesis regulations and feedback inhibition, identify clinical disorders of purine degradation, describe Leshnyhan syndrome and gout, describe nucleotide digestion, and outline the treatment for hyperuricemia and gout.

Importance of Nucleotides

  • Nucleotides are the building blocks of DNA and RNA.
  • They are crucial for genome replication, transcription of genetic information.
  • Act as carriers for activated intermediates in carbohydrate, lipid, and protein synthesis, like UDP-glucose for glycogen formation.
  • Form coenzymes (e.g., Coenzyme A, FAD, NAD+, NADH+).
  • ATP is the primary energy currency, with GTP also serving as an energy source.
  • ATP acts as a phosphoryl donor, transferred by protein kinase.
  • cAMP and cGMP act as secondary messengers in signal transduction pathways.
  • Nucleotide biosynthesis is vital for drug development, as many anticancer drugs target steps in DNA synthesis.

Nucleotide Structure

  • A nucleotide consists of a nitrogenous base, a pentose sugar (ribose or deoxyribose), and a phosphate group.
  • Nitrogenous bases are either purines (adenine, guanine) or pyrimidines (cytosine, thymine, uracil).
  • The phosphate group can have 1, 2, or 3 phosphates.

Nucleic Acids - Bases

  • Nucleic acid information is encoded in base sequences.
  • Bases are derived from purine (adenine, guanine) and pyrimidine (cytosine, thymine, uracil) heterocycles.
  • Uracil replaces thymine in RNA.

Unusual Bases

  • Some DNA and RNA contain unusual bases.
  • Base modifications (e.g., methylation, glycosylation, amination, acetylation, and reduction) can occur.
  • Unusual bases aid in nucleotide recognition by specific enzymes or protect against degradation.

Pentoses in Nucleic Acids

  • Ribose is the pentose sugar in RNA.
  • Deoxyribose is the pentose sugar in DNA.

Nucleotides as Phosphate Esters

  • Nucleotides are mono-, di-, or triphosphate esters of nucleosides.
  • The first phosphate group is attached to the 5' carbon of the pentose sugar.
  • The phosphate groups carry negative charges, making DNA and RNA acidic.

Nomenclature of Bases, Nucleosides, and Nucleotides

  • Tables detailing the nomenclature of bases, nucleosides, and nucleotides in RNA and DNA are provided, referencing the base, ribonucleoside vs deoxyribonucleoside, and ribonucleotide vs deoxyribonucleotide.

Biosynthesis of Nucleotides - Two Pathways

  • De novo pathways: Synthesize nucleotides from simpler precursors (PRPP, amino acids, ATP, CO2, etc.).
  • Salvage pathways: Synthesize nucleotides from pre-formed bases.

Biosynthesis of Pyrimidine Nucleotides

  • The first step is the synthesis of carbamoyl phosphate; this occurs in the cytosol.
  • The synthesis is a phosphate transfer reaction without net oxidation or reduction.
  • Step 2: Carbamoyl phosphate is coupled to aspartate to form carbamoylaspartate, then orotate.
  • Step 3: Oroate is coupled to PRPP to form orotate, then uridylate.

Biosynthesis of Purine Nucleotides

  • Committed step: Glutamine is used to produce 5-phosphoribosyl-1-amine.
  • Multiple steps to form IMP (inosine monophosphate).
  • IMP is a precursor to AMP (adenine monophosphate) and GMP (guanine monophosphate).

Regulation of Pyrimidine Biosynthesis

  • Feedback inhibition by UTP, activated by ATP and PRPP.
  • Feedback inhibition of aspartate transcarbamoylase (inhibited by CTP and stimulated by ATP.)

Salvage Pathway of Pyrimidines

  • Only 30% of pyrimidine nucleotides are formed via salvage pathways.
  • Salvage pathway involves uptake of pyrimidine nucleosides (not free bases.).

Degradation of Nucleotides

  • Pyrimidines degrade to CO2 and NH4.
  • Purine bases are degraded to uric acid and related compounds (hypoxanthine, xanthine).
  • Xanthine oxidase is crucial for purine degradation and generating uric acid.

Diseases Associated with Purine Degradation

  • Lesch-Nyhan syndrome: Inherited disorder with HGPRT deficiency, resulting in excessive uric acid accumulation, self-mutilation, and neurological problems.
  • Adenine Defficiency syndrome (ADA) : ADA enzyme deficiency leads to a severe immune deficiency.
  • Gout: Uric acid crystal deposition in joints, often associated with excessive uric acid production or excretion problems.

Degradation of Dietary Nucleic Acids in the Small Intestine

  • Ribonucleases and deoxyribonucleases break down DNA and RNA into oligonucleotides.
  • Phosphodiesterases further break down oligonucleotides into nucleotides.
  • Nucleosidases remove phosphate from nucleotides, leaving nucleosides.
  • Nucleosides can be absorbed or converted into bases.

Urate Benefits and Diseases:

  • Urate is a byproduct of purine metabolism.
  • Uric acid is an antioxidant, potentially contributing to human longevity.
  • High uric acid (hyperuricemia) can cause gout and kidney problems.
  • Genetic mutations can affect nucleotide synthesis & degradation, leading to diseases.

Summary

  • Two main nucleotide synthesis pathways (de novo and salvage).
  • Pyrimidine synthesis involves constructing the pyrimidine ring, and then attaching it to PRPP.
  • Purine synthesis involves constructing the purine ring on a sugar template.
  • Nucleotide biosynthesis regulated.
  • Degradation pathways for both purines (uric acid production) and pyrimidines.
  • Diseases can arise from issues in either nucleotide synthesis or degradation.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

PHBC 522 Biochemistry I Lecture 7 - Nucleotide Metabolism (Winter 2024) PDF

Description

This quiz focuses on the roles of key enzymes, such as thymidylate synthase, in nucleotide synthesis, along with the functions of nucleotides in biological systems. It also covers conditions related to nucleotide metabolism, including orotic aciduria and hyperuricemia. Test your knowledge on the essential components and pathways involved in DNA and RNA synthesis.

More Like This

Use Quizgecko on...
Browser
Open
Browser
Browser