Chapter 26: Nucleotide Biosynthesis

What are the pyrimidine bases and what are they attached to?

Cytosine, Thymine, Uracil; Attached TO ribose

How are purine bases assembled?

Purine bases (Adenine, Guanine) are assembled ON the ribose.

How are deoxyribonucleotides synthesized?

Deoxyribonucleotides are synthesized from corresponding ribonucleotides.

Are de novo biosynthesis pathways conserved among species?

Yes, pathways are conserved among species.

What is missing from parasites like Falciparum in terms of de novo biosynthesis?

Compounds that inhibit salvage pathways.

What type of drugs are used against parasites like Falciparum?

Antiparasitic drugs.

What are salvage pathways in relation to nucleotides?

Purine or pyrimidine bases are salvaged from the turnover of nucleotides or from the diet.

What is a free base in the context of salvage pathways?

A free base is attached to ribose.

What enzyme makes carbamoyl phosphate from bicarbonate and ammonia in the de novo synthesis of pyrimidine?

Carbamoyl phosphate synthetase

What is the committed step in the de novo synthesis of pyrimidine?

Aspartate transcarbamoylase (ATCase) converts carbamoyl phosphate to carbamoylaspartate

What happens to carbamoylaspartate in the de novo synthesis of pyrimidine?

Carbamoylaspartate cyclizes to form Orotate

How is UMP formed in the de novo synthesis of pyrimidine?

Link orotate to PRPP to make UMP

What are the products of UMP phosphorylation in the de novo synthesis of pyrimidine?

UDP and UTP

CTP is made from UTP

CTP is an allosteric inhibitor of ATCase

What is the starting molecule for the De Novo Synthesis of Purines?

PRPP (the activated form of ribose 5'-phosphate)

What is the committed step in the De Novo Synthesis of Purines?

The conversion of PRPP into 5-phosphoribosyl-1-amine

What inhibits the committed step in the De Novo Synthesis of Purines?

Several intermediates including IMP, AMP, and GMP

What is the end product of the De Novo Synthesis of Purines?

IMP (inosine monophosphate)

What can IMP be converted into?

GMP (Guanylate) or AMP (Adenylate)

What type of pathway is the De Novo Synthesis of Purines?

A branched pathway

During De Novo Synthesis of Purines, how is the base synthesized?

While attached to ribose

What are the products of ribonucleotide reductase?

ADP, GDP, CDP, and UDP

What do ADP, GDP, CDP, and UDP convert into?

dADP, dGDP, dCDP, and dUDP

What are the final deoxyribonucleotides produced from dADP, dGDP, dCDP, and dUDP?

dATP, dGTP, dCTP, dTTP

What is the methyl donor for Thymidylate Synthase?

Methylene-tetrahydrofolate

What is the product of the oxidation of methylene-tetrahydrofolate in Thymidylate Synthase?

Dihydrofolate

Which enzyme catalyzes the first step in the regeneration of dihydrofolate?

Dihydrofolate reductase

Dihydrofolate Reductase

dihydrofolate to tetrahydrofolate via NADPH and H+

What do anticancer drugs block in the synthesis of DNA?

dTMP

What type of cells do anticancer drugs mainly harm?

Rapidly dividing cells

Which drugs inhibit dihydrofolate reductase?

Aminopterin and methotrexate

What is the mechanism of action of Fluorouracil?

It inhibits thymidylate synthase as a suicide inhibitor.

What is a consequence of Folic Acid (B9) deficiency?

Causes uracil to be incorporated into DNA (targeted by repair mechanisms)

What is a health risk associated with Folic Acid (B9) deficiency?

Deficiency is associated with cancer, heart disease, and neurological impairment

Why is Folic Acid (B9) especially important during pregnancy?

It is important during rapid cell division to prevent neural tube defects like spina bifida

What leads to the production of urate in gout?

Degradation of purines

Where do urate crystals precipitate in gout?

In joints and kidneys

What types of foods should be reduced to manage gout?

Foods rich in purines, such as red meat and tofu