15-16 - Introduction to Nucleic Acids; Biosynthesis of Purines and Pyrimidines

lectures 15+16

A patient receiving high-dose methotrexate for cancer develops mouth sores and a low white blood cell count. Which enzyme does methotrexate inhibit, and why does it also harm healthy cells?

dihydrofolate reductase (DHFR); it attacks healthy cells that divide rapidly

A kidney transplant recipient is prescribed mycophenolate to prevent rejection. Which enzyme does mycophenolate block, and why are lymphocytes especially sensitive?

inosine monophosphate dehydrogenase (IMPDH);

A patient with recurrent gout isprescribed allopurinol to lower uric acid. Which enzyme does allopurinol inhibit, and why does that help prevent future gout attacks?

xanthine oxidase;

What do nucleotides build?

DNA and RNA

What gets broken down by nucleotides?

uric acid (from purines)

What is a nucleotide?

base + sugar + phosphate (AMP)

What are examples of purines?

adenine and guanine

What are examples of pyrimidines?

cytosine, thymine, and uracil

How many rings do purines contain?

2

How many rings do pyrimidines contain?

1

Nucleotides are joined by _______ bonds to form a sugar-phosphate backbone

phosphodiester

____ builds nucleotides from smaller precursors, using energy and multiple enzyme-catalyzed reactions.

De novo synthesis

____ reuse preformed bases to make nucleotides; recycling generally requires less energy than building the bases from the beginning.

Salvage pathways

Xanthine oxidase inhibitors lower _____ production over time.

uric acid

A 45-year-old patient receiving high-dose methotrexate for cancer develops painful mouth sores and a low white blood cell count. Which mechanism best explains these adverse effects?

Methotrexate inhibits DHFR, reducing active folate (THF) availability for nucleotide synthesis in rapidly dividing normal
cells.

A patient with recurrent gout is started on allopurinol. Which statement correctly describes how allopurinol lowers serum uric acid?

It inhibits xanthine oxidase, reducing conversion of hypoxanthine to xanthine and of xanthine to uric acid

What is the main function of DNA?

DNA stores the cell's genetic information.

What is transcription?

the process of using DNA as a template to make RNA in the nucleus.

What is translation?

: The process of using mRNA to make proteins on ribosomes in the cytoplasm.

Where does transcription occur?

nucleus

Where does translation occur?

On ribosomes in the cytoplasm.

What is mRNA (Messenger RNA) ?

It carries genetic instructions from DNA to ribosomes, where proteins are made.

What is the purpose of DNA replication?

To make a copy of DNA before cell division.

Why do dividing cells need a steady supply of nucleotides?

they need nucleotides to make new DNA during DNA replication.

What are some examples of proteins made through translation?

• Enzymes

• Receptors

• Antibodies

• Some hormones

What are nucleic acids?

Long chains (polymers) made up of nucleotide units.

What are the three components of a nucleotide?

1. Nitrogenous base

2. Five-carbon sugar

3. One or more phosphate groups

What is a nucleoside?

A nitrogenous base attached to a sugar WITHOUT a phosphate group.

What is a nucleotide?

A nitrogenous base attached to a sugar WITH one or more phosphate groups.

What is the main difference between a nucleoside and a nucleotide?

Is adenosine a nucleoside or nucleotide?A nucleotide contains phosphate groups, while a nucleoside does not.

Is adenosine a nucleoside or nucleotide?

Nucleoside. It contains adenine and ribose without phosphate.

Is AMP a nucleoside or nucleotide?

Nucleotide. AMP (adenosine monophosphate) contains adenosine and one phosphate group.

How are the five carbons of a nucleotide sugar numbered?

1′, 2′, 3′, 4′, and 5′.

Where is the nitrogenous base attached to the sugar?

1’ carbon

Where is the phosphate group commonly attached to the sugar?

5′ carbon.

What is the function of the 3′-OH group?

It allows the growing DNA or RNA strand to be extended by adding more nucleotides.

What is the difference between ribose and deoxyribose?

• Ribose has an OH group at the 2′ carbon.

• Deoxyribose has a hydrogen instead of an OH group at the 2′ carbon.

Which sugar is found in RNA?

ribose

Which sugar is found in DNA?

Deoxyribose.

What does "deoxy" mean in deoxyribose?

It means one less oxygen compared with ribose at the 2′ carbon.

What are the two families of nitrogenous bases?

• Purines

• Pyrimidines

What is the structure of a purine?

A nitrogenous base with TWO rings.

Which two nitrogenous bases are purines?

• Cytosine (C)

• Adenine (A)

• Thymine (T)

• Uracil (U)

• Guanine (G)

A and G

Which three nitrogenous bases are pyrimidines?

• Cytosine (C)

• Adenine (A)

• Thymine (T)

• Uracil (U)

• Guanine (G)

C, T, U

Which nitrogenous base is found in RNA instead of thymine?

Uracil (U)

Which nitrogenous base is found in DNA instead of uracil?

Thymine (T).

What are three important functions of nucleotides besides building DNA and RNA?

1. Energy transfer

2. Cell signaling

3. Supporting metabolism

Which nucleotides participate in energy transfer?

• ATP

• GTP

What is the role of cAMP?

It participates in cell signaling.

Which nucleotide-containing cofactors support metabolism?

• NAD⁺

• FAD

• Coenzyme A

What are DNA and RNA made of?

polymers (long chains) made of nucleotides.

What are the two ends of a DNA or RNA strand called?

• 5′ end

• 3′ end

What type of bond connects nucleotides together in DNA and RNA?

Phosphodiester bonds.

What is a phosphodiester bond?

A bond in which a phosphate connects the 3′ carbon of one sugar to the 5′ carbon of the next sugar.

Why does a DNA or RNA strand have a 5′ end and a 3′ end?

Because nucleotides connect in a specific direction, creating two chemically different ends.

In what direction are DNA and RNA sequences conventionally written?

From 5′ to 3′.

What group is typically found at the 5′ end of a nucleic acid strand?

A phosphate group.

What group is typically found at the 3′ end of a nucleic acid strand?

A hydroxyl (OH) group.

Which bases pair together in DNA?

• Adenine (A) pairs with Thymine (T).

• Guanine (G) pairs with Cytosine (C).

Where are the sugar-phosphate backbones located in the DNA double helix?

On the outside of the double helix.

Where are the nitrogenous bases located in the DNA double helix?

On the inside, where they pair with complementary bases.

What holds the DNA double helix together?

Hydrogen bonding and base stacking.

What is base stacking?

The interaction between neighboring bases that helps stabilize the DNA double helix.

. What does antiparallel mean in DNA?

The two DNA strands run in opposite directions. One runs 5′ to 3′, while the other runs 3′ to 5′.

What is the complementary strand of 5′–ATGC–3′?

3′–TACG–5′

What are the complementary DNA base-pairing rules?

• A pairs with T.

• T pairs with A.

• G pairs with C.

• C pairs with G.

How many hydrogen bonds form between A and T?

Two hydrogen bonds.

How many hydrogen bonds form between G and C?

Three hydrogen bonds.

Why is GC-rich DNA generally more stable?

G-C pairs form three hydrogen bonds, compared with two for A-T pairs, contributing to greater stability.

What is the melting temperature of DNA?

the temperature at which 50% of double-stranded DNA (dsDNA) dissociates into single-stranded DNA (ssDNA)

What happens to the melting temperature when DNA contains more G-C pairs?

the melting temperature generally increases.

Besides base pairing, what other factors influence DNA strand stability?

• Base stacking

• Salt concentration

• DNA sequence

What is the main function of DNA?

: Long-term storage of genetic information.

What is the main function of RNA?

RNA performs multiple roles in using genetic information, including helping make proteins.

What is the human genome?

The complete set of genetic information contained in human DNA.

Approximately how many base pairs are in one set of the human nuclear genome?

3 billion

How many chromosomes are in one set of the human genome?

23 chromosomes

How many chromosomes are found in most human body cells?

46 chromosomes, organized into 23 pairs.

Why do most human body cells have 46 chromosomes?

They inherit one set of 23 chromosomes from each parent.

How many pairs of autosomes do humans have?

22 pairs

What are autosomes?

Chromosomes that are not sex chromosomes.

What are the two s-x chromosome combinations in humans?

• XX = typically female

• XY = typically male

How many chromosomes are found in sperm and egg cells?

23 chromosomes (one set).

Why do sperm and egg cells contain only 23 chromosomes?

So that when they combine during fertilization, the resulting cell has 46 chromosomes.

Do mitochondria contain their own DNA?

Yes. Mitochondria have a small, separate, circular genome.

How is DNA organized inside chromosomes?

DNA is packaged with proteins to form chromatin, which makes up chromosomes.

What is chromatin?

DNA packaged and organized with proteins, including histones.

What is a gene?

A segment of DNA that contains instructions for making a functional RNA or protein.

Approximately how many protein-coding genes do humans have?

about 20,000.

What percentage of the human genome actually codes for proteins?

1–2%

What is the general flow of genetic information?

DNA → RNA → Protein.

What is the relationship between DNA, chromosomes, and genes?

DNA contains genetic information, chromosomes are DNA packaged with proteins, and genes are specific sections of DNA that provide instructions for functional RNA or proteins.

What are the two main ways cells obtain nucleotides?

1. De novo synthesis

2. Salvage pathways

What is de novo nucleotide synthesis?

Making new nucleotides from smaller starting materials (precursors).

Does de novo synthesis require energy?

Yes. It requires energy and multiple enzyme-catalyzed reactions.

What is a nucleotide salvage pathway?

A pathway that recycles preformed nitrogenous bases and nucleosides to make nucleotides.

Which pathway generally requires less energy: de novo synthesis or salvage?

Salvage pathways because they recycle existing bases and nucleosides instead of building them from scratch.

What is the main difference between de novo synthesis and salvage pathways?

• De novo: Builds nucleotides from smaller precursors.

• Salvage: Recycles existing bases and nucleosides to make nucleotides.

Why are nucleotide synthesis pathways important drug targets?

Rapidly dividing cells need large amounts of nucleotides to make new DNA and RNA, so blocking nucleotide production can slow cell growth and division.

What are purines?

Nitrogenous bases with two rings. The two purines are adenine and guanine.