Pyrimidine

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Definition

noun

plural: pyrimidines

py·rim·i·dine, [py·rim·i·dine]


A heterocyclic aromatic compound that presents as a pyrimidine ring, and serves as a component of nucleic acids (e.g. DNA and RNA), certain proteins, starches, etc.

Details

Overview

A nucleobase is a nitrogen-containing compound that when attached to a pentose sugar ribose or deoxyribose forms nucleotide. Nucleotide is the monomeric unit of nucleic acids, such as DNA and RNA. In two-stranded nucleic acids like DNA, the nucleobases are paired. The two nucleobases that are complementary are connected by a hydrogen bond. The nucleobases can be grouped into two major types: purines and pyrimidines.


Purines vs. Pyrimidines

While both purines and pyrimidines are heterocyclic aromatic compounds, they can be differed from each other based on the chemical structure. A purine has two carbon rings whereas a pyrimidine has one carbon ring. The purine has a pyrimidine ring fused to an imidazole ring. The pyrimidine has only a pyrimidine ring. Thus, the purine has four nitrogen atoms whereas the pyrimidine has two.


Pyrimidines include cytosine, thymine, and uracil whereas purines include adenine and guanine. These five nitrogenous bases are regarded as primary or canonical since they are the fundamental units of the genetic code. The nucleobases that make up the nucleic acid are used to distinguish DNA from RNA molecules. In DNA, thymine complementary pairs with adenine whereas in RNA, uracil matches with adenine. The thymine differs from uracil in having a methyl group, which the uracil lacks. The pairings of nucleobases C-G and A-T (or A-U in RNA) are referred to as base complements.


Properties of Pyrimidines

Pyrimidine is a heterocyclic aromatic organic compound with a chemical formula of C4H4N2. It has a single ring (called a pyrimidine ring) with alternating carbon and nitrogen atoms. The molar mass of pyrimidine is 80.088 g/mol and its melting point is at 20-22 °C.


Cytosine, Thymine, and Uracil

Cytosine, thymine, and uracil are pyrimidine nucleobases. Cytosine can be distinguished from the other pyrimidines by having a keto group at position 2 and an amine group at position 4 in its heterocyclic aromatic ring. It has a chemical formula of C4H5N3O. In DNA and RNA, cytosine matches with guanine forming three hydrogen bonds. When phosphorylated with three phosphoric acid groups, they become cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP), which are nucleotides that build up RNA and DNA molecules, respectively. A cytidine triphosphate is a nucleotide that forms part of DNA or RNA. It may also serve as a co-factor to enzymes. It can transfer its phosphate to convert ADP to ATP.


Thymine has a chemical formula of C5H6N2O2. It has two keto groups at positions 2 and 4, and a methyl group at position 5 in its heterocyclic aromatic ring. Thymine complementary base pairs with adenine by two hydrogen bonds. However, unlike cytosine that is present in both DNA and RNA, thymine is present only in the DNA molecule because it is replaced by uracil in RNA. Thymine that is attached to a deoxyribose (a pentose sugar) is referred to as deoxythymidine (or thymidine). When phosphorylated with three phosphoric acid groups, the deoxythymidine becomes deoxythymidine triphosphate (dTTP), which is one of the nucleotide monomeric units that build up DNA.


Uracil is similar to thymine in terms of structure except for the methyl group at position 5 in the heterocyclic aromatic ring present in thymine. It has a chemical formula of C4H4N2O2. In complementary base pairing, uracil pairs with adenine. In general, uracil occurs in RNA, not in DNA. Instead of uracil, DNA has thymine that pairs with adenine. One of the possible explanations why DNA has thymine instead of uracil is associated with the conversion of cytosine into uracil by spontaneous deamination. Cytosine can turn into uracil when it loses its amine group. This deamination of cytosine is a common occurrence. Nevertheless, the error is corrected through an inherent DNA repair systems. If not repaired though, it could lead to point mutation. If uracil is present in the DNA, the repair systems may not be able to distinguish the original uracil from the cytosine-turned-uracil and therefore may fail to discern which uracil to correct. The presence of methyl group in thymine (which is absent in uracil) helps avert this from happening, thereby, preserving the integrity and stability of the genetic code. Uracil that is attached to a deoxyribose (a pentose sugar) is referred to as uridine. When phosphorylated with three phosphoric acid groups, uridine becomes uridine triphosphate (UTP), which is one of the nucleotide monomeric units that build up RNA.


Common biological reactions

Biosynthesis

In pyrimidine biosynthesis, the ring forms by a series of steps that begins in the formation of carbamoyl phosphate. First, carbamoyl phosphate is produced from biochemical reaction involving bicarbonate, glutamine, ATP (for phosphorylation), and water molecule. The enzyme that catalyzes the reaction is carbamoyl phosphate synthetase II located in the cytosol. Next, the carbamoyl phosphate is converted into carbamoyl aspartate by the enzyme aspartate transcarbamylase. Then, the ring closes through intramolecular condensation, converting carbamoyl phosphate into dihydroorotate by the enzyme dihydroorotase. Lastly, the dihydroorotate is oxidized by dihydroorotate dehydrogenase (an integral membrane protein in the inner mitochondrial membrane) to convert into orotate. As a result, C2 of the pyrimidine ring comes from the bicarbonate ion (HCO3-), N3 comes from glutamine, and the rest of the atoms in the rings are derived from aspartate. After the pyrimidine ring forms, 5-phospho-α-D-ribosyl 1-pyrophosphate (PRPP), a ribose phosphate, reacts to orotate to form orotidine-5-monophosphate (OMP). OMP is then decarboxylated by the enzyme OMP decarboxylase to yield uridine monophosphate (UMP). Eventually, uridine diphosphate (UDP) and uridine triphosphate (UTP) are produced down the biosynthetic pathway by kinases and dephosphorylation of ATPs. UTP can be converted into cytidine triphosphate (CTP) by amination of UTP via the enzyme CTP synthetase.[1]


Pyrimidine biosynthesis differs from purine biosynthesis in a way that purines are synthesized as a nucleotide first whereas pyrimidines form initially as a free base. In humans, pyrimidines are synthesized in various tissues, especially in spleen, thymus, and gastrointestinal tract.


Pyrimidine salvage

Pyrimidines that are degraded can be recycled by a salvage pathway. Nucleobases are recovered for re-use post-RNA and DNA degradations. Pyrimidine salvage pathways are as follows:

  • Cytosine is converted into uracil by deamination. By uridine phosphorylase, uracil is converted into uridine by reacting with ribose-1-phosphate. Through the enzyme nucleoside kinase, uridine is converted into uridine monophosphate (UMP).
  • Thymine is converted into thymidine by reacting with deoxyribose-1-phosphate and by the enzyme thymidine phosphorylase. Thymidine is then converted into thymidine monophosphate by the enzyme nucleoside kinase.


Biological function

Pyrimidines as one of the nucleobases are important structural components of nucleic acids. Nucleic acids such as DNA and RNA molecules contain the genetic information important for all cellular functions and heredity. Apart from the nucleic acids, nucleobases are also important components of certain proteins and starches. Thus, their functions are not just to serve as structural constituents of DNA and RNA but they are also involved in the regulation of enzymes and cell signaling.



Supplementary

IUPAC

  • 1,3-Diazine
  • m-Diazine

Chemical formula

  • C4H4N2

Derived term(s)



Further reading

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See also



Reference

  1. Charma, K. & Somani, D. (2015). Pyrimidine Biosynthesis. Retrieved from Slideshare.net website: [Link]



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