Nucleotide Metabolism Overview
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Questions and Answers

What are the three structural components of a nucleotide?

Ribose, Base, Phosphate

Which of the following are purines?

  • Uracil
  • Guanine (correct)
  • Thymine
  • Adenine (correct)
  • Cytosine

What are some examples of nucleotide triphosphates?

ATP, GTP, CTP, UTP

Signaling molecules, such as cAMP and cGMP, induce molecular changes inside cells.

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

ADP is a structural component of many enzyme cofactors.

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

What is the name of the enzyme that removes phosphate from nucleotides?

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

What is the name of the enzyme that removes sugar from nucleosides?

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

Salvage reactions involve the recycling of intact bases for inter-conversions.

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

What is the name of the degradation product of purine nucleotides?

<p>Uric acid</p> Signup and view all the answers

What is the name of the disease characterized by elevated levels of uric acid?

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

What is the name of the drug used for the treatment of gout?

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

What are the three major steps in the biosynthesis of purines?

<p>Formation of PRPP, assembly of the purine ring, and conversion of IMP to AMP or GMP</p> Signup and view all the answers

What is the name of the activated sugar used for purine and pyrimidine biosynthesis?

<p>5-Phosphoribosyl 1-pyrophosphate (PRPP)</p> Signup and view all the answers

The pyrimidine ring is formed before the attachment of ribose phosphate.

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

What is the name of the enzyme that converts dUMP to dTMP?

<p>Thymidylate Synthase</p> Signup and view all the answers

Tetrahydrofolate is a cofactor in the methyl group transfer reaction in the biosynthesis of dTMP.

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

Which of the following are pyrimidine bases?

<p>Uracil (B), Cytosine (D), Thymine (E)</p> Signup and view all the answers

What is the name of the enzyme responsible for removing phosphate from nucleotides?

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

What is the name of the enzyme responsible for removing sugar from nucleosides?

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

What is the name of the enzyme that catalyzes the conversion of hypoxanthine to xanthine?

<p>Xanthine oxidase or xanthine dehydrogenase</p> Signup and view all the answers

What is the final product of purine catabolism in humans?

<p>Uric acid</p> Signup and view all the answers

High-nucleotide diets can lead to gout.

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

What is the name of the drug used to treat gout?

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

What are the two main products of pyrimidine catabolism?

<p>Acetyl CoA or succinyl CoA</p> Signup and view all the answers

The purine ring is assembled around the N attached to the ribose phosphate.

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

The pyrimidine ring is assembled before attachment of the ribose phosphate.

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

What are the two enzymes involved in the first reaction of pyrimidine biosynthesis?

<p>Glutamine and carbamoyl phosphate synthetase II</p> Signup and view all the answers

What is the final reducing agent in the biosynthesis of deoxyribonucleotides?

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

What is the name of the enzyme involved in methyl group transfer in the formation of dTMP from dUMP?

<p>Thymidylate synthase</p> Signup and view all the answers

What is the name of the coenzyme involved in methyl group transfer?

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

Which of the following are purines? (Select all that apply)

<p>Adenine (B), Guanine (C)</p> Signup and view all the answers

What are the three main types of nucleotide triphosphates?

<p>ATP, GTP, CTP, UTP</p> Signup and view all the answers

What are some examples of signaling molecules that involve nucleotides?

<p>cAMP, cGMP, ppGpp</p> Signup and view all the answers

What is a common example of a coenzyme that is structurally related to ADP?

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

Name the two electron carriers discussed in the context of enzyme cofactors.

<p>NAD(P)+ and FAD</p> Signup and view all the answers

What type of molecule is broken down to create uric acid?

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

Allopurinol, a drug used for GOUT, is structurally similar to Hypoxanthine.

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

What are the two main products of the degradation of pyrimidine nucleotides?

<p>β-Alanine, β-Aminoisobutyrate</p> Signup and view all the answers

What molecule is formed first in the biosynthesis of new purines?

<p>5-phosphoriboxyl 1-pyrophosphate (PRPP)</p> Signup and view all the answers

What is the first reaction involved in the biosynthesis of new pyrimidines?

<p>Glutamine + HCO3 + 2 ATP + H2O → Carbamoyl phosphate + Glutamate + 2 ADP + Pi</p> Signup and view all the answers

In purine biosynthesis, the purine ring is assembled around the N attached to the ribose phosphate.

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

In pyrimidine biosynthesis, the ribose-5-phosphate attaches to the pyrimidine ring after the ring itself is formed.

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

What are the primary roles of fluorouracil, a common anticancer drug?

<p>Inhibit the thymidylate synthase enzyme</p> Signup and view all the answers

What is the final reducing agent for deoxyribonucleotide synthesis?

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

Most deoxyribonucleotides are synthesized directly from deoxyribose.

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

Methotrexate and Amphopterin are anticancer drugs that target dihydrofolate reductase.

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

Which two essential amino acids are involved in the synthesis of cysteine?

<p>Methionine and Serine</p> Signup and view all the answers

In humans and animals, cysteine is considered a conditional non-essential amino acid.

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

Flashcards

Nucleotide catabolism

The breakdown of nucleotides into simpler components.

Nucleotide anabolism

The synthesis of nucleotides from simpler components.

Purine degradation

The breakdown of purine nucleotides (AMP, GMP).

Pyrimidine degradation

Breakdown of pyrimidine nucleotides (CMP, UMP, dTMP).

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Salvage reactions

Recycling of intact bases for reuse in nucleotide synthesis.

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Purine biosynthesis

The synthesis of purine nucleotides.

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Pyrimidine biosynthesis

Synthesis of pyrimidine nucleotides.

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Deoxyribonucleotide biosynthesis

Synthesis of deoxyribonucleotides from ribonucleotides.

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GOUT

A disease caused by high uric acid levels.

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Allopurinol

A drug used to treat gout by inhibiting xanthine oxidase.

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Nucleotide triphosphates

Nucleotides with three phosphate groups (e.g., ATP, GTP).

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Signaling molecules

Nucleotides that act as messengers.

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Enzyme cofactors

Nucleotides that are parts of enzyme co-factors.

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Nucleic acid monomers

Building blocks of DNA and RNA.

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Nucleotides

Monomeric units of nucleic acids.

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Purines

A type of nitrogenous base in nucleic acids.

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Pyrimidines

A type of nitrogenous base in nucleic acids.

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PRPP

5-phosphoriboxyl-1-pyrophosphate, important in nucleotide biosynthesis.

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Anticancer drugs

Drugs that target nucleotide metabolism to combat cancer.

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Uric acid

End product of purine catabolism.

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What are nucleotides?

They're the building blocks of DNA and RNA, composed of a sugar, a base, and a phosphate.

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What are the 3 components of a nucleotide?

A sugar (ribose or deoxyribose), a nitrogenous base (purine or pyrimidine), and a phosphate group.

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Purines vs. Pyrimidines

Purines are double-ringed structures (adenine and guanine), while pyrimidines are single-ringed structures (cytosine, thymine, and uracil).

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What are nucleotide triphosphates?

Nucleotides with three phosphate groups, like ATP, GTP, CTP, and UTP.

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What are signaling molecules?

Nucleotides that act as messengers, influencing cellular processes, like cAMP and cGMP.

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What are enzyme cofactors?

Nucleotides that are part of enzymes, helping them function properly, like NAD(P)+ and FAD.

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What is nucleotide catabolism?

The breakdown of nucleotides into simpler molecules.

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What is nucleotide anabolism?

The synthesis of nucleotides from simpler molecules.

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How are purines degraded?

Purines are broken down into uric acid, which is excreted in urine.

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What is GOUT?

A disease caused by high levels of uric acid, leading to painful inflammation in joints.

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How does Allopurinol work?

Allopurinol treats gout by inhibiting xanthine oxidase, an enzyme involved in uric acid production.

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How are pyrimidines degraded?

Pyrimidines are broken down into simpler molecules, like ammonia and carbon dioxide.

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What are salvage reactions?

These are pathways that recycle intact bases for reuse in nucleotide synthesis.

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How are purines synthesized?

The purine ring is assembled around the ribose phosphate, with different atoms coming from various sources.

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How are pyrimidines synthesized?

The pyrimidine ring is assembled before attaching to ribose phosphate.

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What is PRPP?

5-phosphoriboxyl 1-pyrophosphate, an activated sugar used in both purine and pyrimidine biosynthesis.

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How are deoxyribonucleotides synthesized?

They are synthesized from their corresponding ribonucleotides by reducing the ribose sugar to deoxyribose.

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What is the role of tetrahydrofolate?

It's a cofactor in the conversion of dUMP to dTMP, providing a methyl group.

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What is the importance of nucleotide metabolism?

Nucleotide metabolism is essential for DNA and RNA synthesis, energy production, and cellular signaling.

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How do anticancer drugs target nucleotide metabolism?

They interfere with nucleotide synthesis or function, slowing down cancer cell growth.

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What is a key difference between purine and pyrimidine degradation?

Purine degradation results in uric acid, while pyrimidine degradation generates simpler molecules like ammonia and carbon dioxide.

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How is PRPP involved in both purine and pyrimidine biosynthesis?

PRPP is used as the activated sugar in both pathways, providing the ribose phosphate backbone for the nucleotides.

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What is the function of aspartate in pyrimidine biosynthesis?

Aspartate provides most of the carbon skeleton for the pyrimidine ring structure.

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What is the role of NADPH in deoxyribonucleotide biosynthesis?

NADPH acts as the final reducing agent in the series of electron transfer reactions that convert ribonucleotides to deoxyribonucleotides.

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How do fluorouracil, methotrexate, and amphopterin inhibit nucleotide metabolism?

Fluorouracil inhibits thymine synthesis; methotrexate and amphopterin block tetrahydrofolate synthesis, preventing dTMP formation.

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Where does carbamoyl phosphate synthetase I function?

It functions in the mitochondrial matrix, catalyzing the first step in pyrimidine biosynthesis, the formation of carbamoyl phosphate.

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What is the difference between carbamoyl phosphate synthetase I and II?

Carbamoyl phosphate synthetase I functions in the mitochondrial matrix for pyrimidine biosynthesis, while carbamoyl phosphate synthetase II functions in the cytosol for urea cycle.

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Amino Acid Oxidation

The breakdown of amino acids for energy, producing ATP.

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Why are amino acids oxidized?

When the body needs energy and dietary carbohydrates and fats are insufficient, amino acids are used as alternative fuel sources.

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Ammonia Removal

The process of eliminating ammonia (NH3), a toxic byproduct of amino acid catabolism.

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Urea Cycle

A metabolic pathway in the liver that converts ammonia into urea, a less toxic compound for excretion.

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Transamination

The transfer of an amino group from an amino acid to α-ketoglutarate, forming glutamate. This occurs in the cytosol.

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Oxidative Deamination

The removal of the amino group from glutamate, generating ammonia and α-ketoglutarate. This happens in the mitochondrial matrix.

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Glutamine Synthesis

In non-liver tissues, ammonia is incorporated into glutamate, forming glutamine, which is transported to the liver.

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Carbamoyl Phosphate Synthetase I

An enzyme in the mitochondrial matrix that catalyzes the synthesis of carbamoyl phosphate from ammonia, CO2, and ATP.

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The Urea Cycle Steps

A series of enzymatic reactions that convert ammonia into urea, involving ornithine, carbamoyl phosphate, citrulline, argininosuccinate, and arginine.

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Urea Excretion

Urea produced in the liver is transported to the kidneys and excreted in urine.

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Glucogenic Amino Acids

Amino acids that can be converted to glucose by gluconeogenesis.

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Ketogenic Amino Acids

Amino acids that can be converted to ketone bodies.

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Tetrahydrofolate (THF)

A cofactor involved in one-carbon group transfer reactions during amino acid metabolism.

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Aspartate Aminotransferase

An enzyme that catalyzes the transfer of an amino group from aspartate to α-ketoglutarate, forming glutamate.

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Methionine Cycle

A series of reactions that recycle methionine and involve a methyl group transfer.

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Branched-Chain Amino Acids

Amino acids with a branched carbon chain, including leucine, valine and isoleucine.

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Tryptophan Degradation

Tryptophan is broken down to acetoacetate and pyruvate.

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Phenylalanine and Tyrosine Degradation

Phenylalanine and tyrosine are broken down to acetoacetate and fumarate.

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Phenylketonuria

A genetic disorder caused by a deficiency in phenylalanine hydroxylase, leading to a build-up of phenylalanine.

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Nitrogen Fixation

The conversion of atmospheric nitrogen (N2) into ammonia (NH3) by nitrogen-fixing bacteria.

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Nitrogenase Complex

A complex of enzymes that catalyzes nitrogen fixation.

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Ammonia Assimilation

The process of incorporating ammonia into organic molecules.

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Essential Amino Acids

Amino acids that cannot be synthesized by the body and must be obtained from the diet.

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Non-Essential Amino Acids

Amino acids that can be synthesized by the body from other precursors.

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Glutamate and Glutamine Synthesis

Glutamate is synthesized from α-ketoglutarate, and glutamine from glutamate.

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Proline and Arginine Synthesis

Proline and arginine are synthesized from glutamate.

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Serine and Glycine Synthesis

Serine is synthesized from 3-phosphoglycerate and glycine from serine.

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Tyrosine Synthesis

Tyrosine is synthesized from phenylalanine.

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Cysteine Synthesis

Cysteine is synthesized from methionine and serine.

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Homocystinuria

A genetic disorder caused by a deficiency in cystathionine β-synthase, leading to a build-up of homocysteine.

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Aspartame

An artificial sweetener composed of phenylalanine and aspartate.

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Study Notes

Nucleotide Metabolism Learning Objectives

  • Nucleotide catabolism and anabolism (biosynthesis) are crucial processes
  • The oxidation of purines and pyrimidines, along with their degradation products, are important to understand
  • Salvage reactions for nucleotides are a key concept
  • The biosynthesis of purines, pyrimidines, and deoxyribonucleotides is essential, along with the flow of Cs and Ns
  • Gout and anticancer drugs relate to nucleotide metabolism, and understanding this relationship is vital

Nucleotides

  • Nucleotides are the fundamental units of DNA and RNA
  • They have three components: ribose, a base, and a phosphate

Purines

  • Adenine and guanine are purine bases
  • Adenine structure described
  • Guanine structure described

Pyrimidines

  • Uracil, thymine, and cytosine are pyrimidine bases
  • Uracil structure described
  • Thymine structure described
  • Cytosine structure described

Other Nucleotide-Containing Biomolecules

  • Nucleotide triphosphates (ATP, GTP, CTP, UTP) are vital energy carriers
  • Sigaling molecules, such as cAMP, cGMP, and ppGpp, regulate cellular processes

Enzyme Cofactors

  • ADP is a structural component in several enzyme cofactors
  • Examples include coenzyme A (CoA) for fatty acyl transfer, and NAD(P)+ and FAD for electron transfer reactions

Degradation of Nucleotides

  • Nucleic acids are broken down into mononucleotides through nucleases
  • Mononucleotides are further broken down through nucleotidases and phosphatases
  • Nucleosides are then broken down by nucleosidases or nucleoside phosphorylases
  • Purines and pyrimidines undergo catabolism, generating degradation products

Catabolism of Purine Nucleotides (AMP and GMP)

  • AMP and GMP are broken down via several enzymatic steps, ultimately generating uric acid

Gout

  • Gout is a disease characterized by high uric acid levels, leading to crystal accumulation and painful joint inflammation
  • Allopurinol is a drug used to treat gout and inhibits xanthine dehydrogenase/oxidase
  • Allopurinol structurally resembles hypoxanthine, a substrate of xanthine dehydrogenase/oxidase

Catabolism of Pyrimidine Nucleotides (CMP, UMP, dTMP)

  • Pyrimidine nucleotides (CMP, UMP, dTMP) are broken down generating acetyl CoA or succinyl CoA in various steps
  • The released nitrogens are further processed into ammonia and urea

Salvage of Purines

  • Purine nucleotides are inter-converted primarily at the monophosphate level, involving reduction, amino group transfer, and oxidation reactions
  • PRPP is a key component in these reactions

Salvage of Pyrimidines

  • Pyrimidine nucleotides are inter-converted at different levels, involving reduction, amino group transfer, reduction, and methylation
  • These reactions convert and recycle nucleotide components

Biosynthesis of New Purines

  • The biosynthesis of new purines begins with the formation of 5-phosphoriboxyl-1-pyrophosphate (PRPP)
  • The purine ring is then assembled on the ribose phosphate
  • Different atoms in the purine ring originate from various sources (e.g., glycine, aspartate, formate, and glutamine amide)

Biosynthesis of New Pyrimidines

  • Pyrimidine ring synthesis occurs before attachment to ribose phosphate
  • The first reaction involves glutamine, bicarbonate, and ATP
  • Carbamoyl phosphate is a crucial intermediate

Formation of UTP from Carbamoyl Phosphate

  • UTP is generated from carbamoyl phosphate, through sequential enzymatic reactions involving aspartate
  • The process involves the attachment of ribose-5-phosphate, forming orotidine-5'-monophosphate and subsequent reactions

Formation of CTP from UTP

  • CTP is produced from UTP by a reaction involving glutamine
  • This step uses ATP as an energy source, and releases ADP as a byproduct

Biosynthesis of Deoxyribonucleotides

  • Deoxyribonucleotides are synthesized from their corresponding ribonucleotides
  • Reduction of ribose to deoxyribose is a crucial step in this process
  • NADPH is the final electron reducing agent

Formation of dTMP from dUMP

  • dTMP is generated from dUMP through a reaction involving tetrahydrofolate
  • Methyl group transfer is essential in forming this nucleotide
  • Serine is the source of the transferred methyl carbon

Azaserine and Acivicin (anti-cancer drugs)

  • Azaserine and Acivicin are drugs that target specific enzymes in nucleotide biosynthesis pathways, inhibiting their activity.

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Description

This quiz covers the essential aspects of nucleotide metabolism, including catabolism and anabolism. It explores purine and pyrimidine structures, salvage pathways, and their implications in health and disease, including gout and cancer treatment. Understand the biochemical processes that involve nucleotides, the building blocks of DNA and RNA.

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