Nucleotide and Purine Synthesis

Nucleotides are composed of a nitrogenous base, a pentose sugar (ribose or deoxyribose), and one, two, or three phosphate groups.

The three pathways are de novo synthesis, salvage pathways, and conversion of ribonucleotides to deoxyribonucleotides.

De novo synthesis is the biosynthesis of nucleotides from simple metabolic precursors like amino acids, ribose-5-phosphate, CO2, and one-carbon units.

Salvage pathways are used to recycle free bases or nucleosides released from nucleic acid breakdown.

The committed step is the synthesis of 5'-phosphoribosylamine by the enzyme glutamine phosphoribosyl pyrophosphate amidotransferase (GPAT).

PRPP (5-phosphoribosyl-1-pyrophosphate) is a key intermediate in purine synthesis. It provides the ribose-5-phosphate backbone for the purine ring.

Ribonucleotide reductase converts ribonucleotides to deoxyribonucleotides, which are essential for DNA synthesis.

Adenylate kinase interconverts AMP, ADP, and ATP, maintaining an equilibrium among these energy carriers in cells.

Lesch-Nyhan syndrome is a rare genetic disorder caused by a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), leading to an accumulation of uric acid in the body.

Methotrexate is a chemotherapy drug that inhibits the enzyme dihydrofolate reductase, which is essential for the synthesis of tetrahydrofolate (THF), a coenzyme needed for nucleotide synthesis. This disrupts DNA and RNA synthesis, slowing down the growth of cancer cells.

Purines are nitrogenous bases found in DNA and RNA. They are composed of a double-ring structure consisting of a pyrimidine ring fused to an imidazole ring.

Ribonucleotides (RNA) contain a ribose sugar, while deoxyribonucleotides (DNA) contain a deoxyribose sugar, which lacks an oxygen atom on the 2' carbon.

Ribonucleotide reductase (RR) converts ribonucleotides into deoxyribonucleotides, providing the building blocks for DNA synthesis.

dATP inhibits the activity of Ribonucleotide reductase, preventing the production of deoxyribonucleotides. It acts as a feedback control mechanism to regulate DNA synthesis.

The salvage pathway reuses free purine bases and nucleosides from degraded DNA and RNA to create new nucleotides, avoiding the energy-intensive de novo synthesis.

Uric acid is the final product of purine degradation in the body. Purine bases are broken down through a series of enzymatic reactions, ultimately forming uric acid.

Gout is a painful inflammatory condition caused by high levels of uric acid in the blood (hyperuricemia), leading to the deposition of uric acid crystals in joints and tissues.

Adenosine deaminase (ADA) is an enzyme crucial for immune development. It breaks down adenosine, a metabolite that can inhibit the production of deoxyribonucleotides. Deficient ADA leads to an accumulation of adenosine, impairing DNA synthesis and immune function.

ADA deficiency causes severe combined immunodeficiency disease (SCID), severely impairing both B and T lymphocyte function, leaving individuals susceptible to severe infections.

Hyperuricemia can be classified into two main categories: uric acid underexcretion (most common) and uric acid overproduction (less common). Underexcretion occurs when the kidneys fail to remove enough uric acid, while overproduction is due to excessive purine breakdown or defective salvage pathways.

Nucleotides are the building blocks of nucleic acids like DNA and RNA. They are also essential components of many coenzymes and energy carriers.

Our bodies can synthesize nucleotides from simpler molecules, making them non-essential nutrients. We don't have to obtain them directly from our diet.

Nucleotides are crucial for energy production. ATP, the primary cellular energy currency, is a nucleotide.

Purines and pyrimidines are the two main classes of nitrogenous bases found in nucleotides. Purines include adenine and guanine, while pyrimidines include cytosine, uracil, and thymine.

Thymine and uracil are both pyrimidines, but thymine has a methyl group attached, while uracil does not.

Some organisms, especially viruses and certain types of RNA, contain unusual bases. These are modified forms of the standard bases.

A nucleoside is a nitrogenous base (purine or pyrimidine) attached to a pentose sugar (ribose or deoxyribose) through an N-glycosidic linkage.

A nucleotide is a nucleoside with one or more phosphate groups attached to the 5'-OH group of the pentose sugar.

Phosphate groups give nucleotides their negative charge, making them important in DNA and RNA structure.

A nucleoside monophosphate has one phosphate group attached, while a nucleoside triphosphate has three phosphate groups.