Bioquímica - Aula 21 - Biossíntese de Nucleotídeos

Summary

In this detailed lecture on biochemistry, Professor Ângelo Cortelazo explores the critical process of nucleotide biosynthesis in living organisms. He delves into the importance of both diet and de novo synthesis in maintaining DNA and RNA production, highlighting the intricate biochemical pathways that enable cellular functions. The lecture covers the role of molecules like PRPP, glutamine, and ATP in constructing purine and pyrimidine bases, with an emphasis on how cancer treatments use drugs to inhibit nucleotide synthesis and disrupt cell division. The discussion integrates concepts of metabolism and enzyme function in a thorough yet engaging manner.

Takeaways

• 😀 The importance of nucleotide biosynthesis in the body, which ensures proper DNA and RNA synthesis.
• 😀 Nucleotides are obtained both from the diet and through de novo synthesis to maintain cellular function.
• 😀 De novo synthesis of nucleotides requires energy, primarily in the form of ATP, and is critical for maintaining metabolic fidelity.
• 😀 Phosphoribosyl pyrophosphate (PRPP) is a key precursor for the synthesis of purine and pyrimidine nucleotides.
• 😀 The construction of purine nucleotides involves complex reactions, using glutamine, glycine, ATP, and other compounds.
• 😀 The biosynthesis of purines (e.g., AMP and GMP) requires various amino acids and energy molecules such as ATP and GTP.
• 😀 Inhibitors of enzymes involved in purine and pyrimidine biosynthesis, like those used in chemotherapy, can slow down tumor cell division by blocking nucleotide production.
• 😀 Pyrimidine bases are synthesized from aspartate and carbamoyl phosphate, and once the base is formed, it is attached to ribose to form nucleotides like UMP and CTP.
• 😀 The conversion of ribonucleotides to deoxyribonucleotides (e.g., thymidine for DNA) involves the reduction of ribose and specific enzymatic processes.
• 😀 Chemotherapy drugs like fluorouracil and methotrexate inhibit critical enzymes in nucleotide metabolism, thus hindering tumor cell growth by blocking DNA replication and transcription.

Q & A

What is the main topic of this biochemistry class?

The main topic of the class is the synthesis of nucleotides, focusing on the process of de novo synthesis and its role in DNA and RNA production in the body.

Why is de novo nucleotide synthesis important?

De novo nucleotide synthesis is important because it replenishes missing nucleotides in the body, ensuring continuous DNA and RNA synthesis. This is crucial for maintaining cell function and preventing metabolic disturbances.

What is PRPP, and how is it involved in nucleotide synthesis?

PRPP (phosphoribosyl pyrophosphate) is a key precursor in nucleotide synthesis. It is formed from ribose 5-phosphate using ATP and is essential for building purine and pyrimidine bases.

What role does glutamine play in the synthesis of purine bases?

Glutamine provides an amine group that is added to the ribose 5-phosphate, starting the construction of purine bases by forming an intermediate called GAR (glycine amidino ribonucleotide).

What is the significance of the enzyme XMP glutamino amidotransferase in cancer treatment?

The enzyme XMP glutamino amidotransferase plays a crucial role in guanine nucleotide synthesis. Inhibiting this enzyme with drugs like asacerine and activicine reduces nucleotide availability, slowing tumor cell division, making it a target for anticancer therapies.

How do chemotherapeutic drugs like fluorouracil and methotrexate work?

Chemotherapeutic drugs like fluorouracil inhibit thymidylate synthase, which is essential for producing thymine. Methotrexate and aminopterin inhibit enzymes involved in nucleotide synthesis, slowing cancer cell division and growth.

What is the difference between purine and pyrimidine base synthesis?

Purine bases are synthesized by building the base on a ribose structure, while pyrimidine bases are synthesized separately and then attached to the ribose. This difference reflects how the structures of the two types of nucleotides are formed.

What is the role of NADPH in the synthesis of deoxyribonucleotides?

NADPH is used in a series of redox reactions to reduce ribonucleotides into deoxyribonucleotides. It donates electrons and protons, allowing the ribose sugar to lose one of its hydroxyl groups and form deoxyribose.

What is the significance of thymidine in DNA synthesis?

Thymidine is a base specific to DNA, and it is synthesized from uridine by the addition of a methyl group. This methylation is essential for the formation of thymine, which is incorporated into DNA.

How do defects in enzymes affect metabolism?

Defects in enzymes or the inhibition of enzymes can disrupt normal metabolic reactions. Even small changes can lead to diseases or metabolic disorders, affecting overall cellular function and leading to conditions like cancer or genetic diseases.