Uracil

Uracil is one of the four nucleobases found in RNA (ribonucleic acid), which is a type of genetic material present in cells. The other three nucleobases in RNA are adenine (A), guanine (G), and cytosine (C). Uracil replaces thymine (T), which is found in DNA (deoxyribonucleic acid).

In RNA, uracil forms base pairs with adenine, similar to the adenine-thymine pairing in DNA. This base-pairing is crucial for the genetic code and the synthesis of proteins during the process of translation.

1.0Structure of Uracil

2.0Synthesis of Uracil

The synthesis of uridine monophosphate (UMP) in organisms, including humans. The de novo pyrimidine biosynthesis pathway is a series of enzymatic reactions that lead to the formation of pyrimidine nucleotides, including uracil.

Synthesis of Orotidine 5 - Monophosphate (OMP): 

The pathway starts with the synthesis of orotidine 5'-monophosphate (OMP). Orotic acid, an intermediate in the pathway, is converted to OMP through a series of enzymatic reactions.

Decarboxylation of OMP to Form Uridine 5'-Monophosphate (UMP): 

The key step in the synthesis of UMP involves the decarboxylation of orotidine 5'-monophosphate (OMP) to form uridine 5'-monophosphate (UMP). This reaction is catalyzed by the enzyme UMP synthase.

The enzyme UMP synthase catalyzes the decarboxylation of OMP, resulting in the removal of a carboxyl group and the formation of UMP. This step is crucial in the conversion of the orotidine derivative to uridine.

Formation of Uridine Diphosphate (UDP) and Uridine Triphosphate (UTP): 

UMP can further be phosphorylated to form uridine diphosphate (UDP) and uridine triphosphate (UTP), which are important nucleotide derivatives.

Incorporation into RNA: 

Finally, UTP can be utilized in RNA synthesis, where it serves as a precursor for the incorporation of uridine into RNA molecules during transcription.

Laboratory methods

1. Hydrolysis of Cytosine: The simplest method involves the addition of water to cytosine, resulting in the production of uracil and ammonia.

• C₄H₅N₃O + H₂O → C₄H₄N₂O₂ + NH₃

2. Condensation of Malic Acid with Urea: A common method is the condensation of malic acid with urea in fuming sulfuric acid.

• C₄H₄O₄ + NH₂CONH₂ → C₄H₄N₂O₂ + 2 H₂O + CO

3. Double Decomposition of Thiouracil: Uracil can be synthesized by double decomposition of thiouracil in aqueous chloroacetic acid.
4. Photo Dehydrogenation of 5,6-diuracil: 5,6-diuracil, synthesized by the reaction of beta-alanine with urea, undergoes photos hydrogenation to produce uracil.

Uracil DNA still exists

Although most cells use uracil for RNA and thymine for DNA, there are exceptions. Some organisms have uracil instead of thymine in all their DNA, and other organisms have uracil in only some of their DNA. 

3.0Uracil in Viral DNA 

Two species of phage (viruses that infect bacteria) are known to have DNA genomes with only uracil and no thymine. We do not yet know whether these phages are representatives of an ancient life form that never evolved thymine DNA, or whether their uracil-substituted genomes are a newly evolved strategy. Nor do we know why these phages use uracil instead of thymine, but it may play an essential role in the life cycle of these viruses. If that is the case, it would make sense for the viruses to ensure that the uracil in their DNA is not replaced with thymine. And one of these phages has in fact been shown to have a gene that encodes a specific protein to inhibit the host’s uracilDNA glycosylase, thus preventing the viral genome from having its uracil ‘repaired’ by the host enzymes

4.0Uses of Uracil

• Enzyme Synthesis : Uracil is involved in the synthesis of enzymes necessary for cell function by bonding with riboses and phosphates.
• Allosteric Regulator and Coenzyme: Uracil serves as an allosteric regulator and coenzyme for reactions in both animals and plants.
• Regulation of Enzyme Activity: UMP controls the activity of carbamoyl phosphate synthetase and aspartate transcarbamoylase in plants. UDP and UTP regulate CPSase II activity in animals.
• Carbohydrate Metabolism: UDP-glucose regulates the conversion of glucose to galactose in the liver and other tissues during carbohydrate metabolism.
• Biosynthesis of Polysaccharides: Uracil is involved in the biosynthesis of polysaccharides and the transportation of sugars containing aldehydes.
• Detoxification: Uracil plays a role in the detoxification of carcinogens found in tobacco smoke. It is required to detoxify certain drugs such as cannabinoids (THC) and morphine (opioids).
• Folate Deficiency and Cancer Risk: In cases of extreme folate deficiency, uracil's role is highlighted in the increased ratio of deoxyuridine monophosphates (dUMP)/deoxythymidine monophosphates (dTMP). This imbalance can lead to uracil misincorporation into DNA and a decrease in DNA production, potentially increasing the risk of cancer.