The thymine is an organic compound consisting of a heterocyclic ring derived from the pyrimidine, a benzene ring with two carbon atoms replaced by two nitrogen atoms. Its condensed formula is C 5 H 6 N 2 O 2, being a cyclic amide and one of the nitrogenous bases that make up DNA.
Specifically, thymine is a pyrimidine nitrogenous base, along with cytosine and uracil. The difference between thymine and uracil is that the former is present in the structure of DNA, while the latter is present in the structure of RNA.
Deoxyribonucleic acid (DNA) is made up of two helices or bands wound together. The exterior of the bands is formed by a deoxyribose sugar chain, the molecules of which are linked through a phosphodiester bond between the 3 'and 5' positions of neighboring deoxyribose molecules.
One of the nitrogenous bases: adenine, guanine, cytosine and thymine, binds to the 1 'position of deoxyribose. The purine adenine base of one helix couples or binds to the pyrimidine base thymine of the other helix through two hydrogen bonds.
Chemical structure
The first image represents the chemical structure of thymine, in which two carbonyl groups (C = O) and the two nitrogen atoms that complete the heterocyclic amide can be seen, and in the upper left corner is the methyl group (–CH 3).
The ring derives from that of pyrimidine (pyrimidine ring), it is flat but not aromatic. The respective number of atoms in the thymine molecule is assigned starting with the nitrogen below.
Thus, C-5 is linked to the group -CH 3, C-6 is the left adjacent carbon atom of N-1, and C-4 and C-2 correspond to the carbonyl groups.
What is this numbering for? The thymine molecule has two hydrogen bond acceptor groups, C-4 and C-2, and two hydrogen bond donor atoms, N-1 and N-3.
In accordance with the above, carbonyl groups can accept C = OH- type bonds, while nitrogens provide NHX type bonds, X being equal to O, N or F.
Thanks to the groups of C-4 and N-3 atoms, thymine pairs with adenine, forming a pair of nitrogenous bases, which is one of the determining factors in the perfect and harmonic structure of DNA:
Thymine tautomers
The image above lists the six possible tautomers of thymine. What are they? They consist of the same chemical structure but with different relative positions of their atoms; specifically, of the H's bound to the two nitrogens.
Maintaining the same numbering of the atoms, from the first to the second, it is observed how the H of the N-3 atom migrates to the oxygen of C-2.
The third also derives from the first, but this time the H migrates to the oxygen of the C-3. The second and fourth are similar but not equivalent, because in the fourth the H comes out of the N-1 and not of the N-3.
On the other hand, the sixth is similar to the third, and as with the pair formed by the fourth and the second, the H emigrates from the N-1 and not from the N-3.
Finally, the fifth is the pure enol form (lactyma), in which both carbonyl groups are hydrogenated in hydroxyl groups (-OH); This is contrary to the first, the pure ketonic form and the one that predominates in physiological conditions.
Why? Probably due to the great energetic stability that this acquires when pairing with adenine by hydrogen bonds and belonging to the structure of DNA.
If not, enol form number 5 should be more abundant and stable, due to its marked aromatic character unlike the other tautomers.
Features
The main function of thymine is the same as the other nitrogenous bases in DNA: to participate in the necessary coding in DNA for the synthesis of polypeptides and proteins.
One of the DNA helices serves as a template for the synthesis of an mRNA molecule in a process known as transcription and catalyzed by the enzyme RNA polymerase. In transcription the DNA bands are separated, as well as their unwinding.
Transcription
Transcription begins when RNA polymerase binds to a region of DNA known as the promoter, initiating mRNA synthesis.
Subsequently, the RNA polymerase moves along the DNA molecule, producing an elongation of the nascent mRNA until it reaches a region of the DNA with the information for the termination of transcription.
There is an antiparallelism in transcription: while the template DNA is read in the 3 'to 5' orientation, the synthesized mRNA has the 5 'to 3' orientation.
During transcription there is a complementary base coupling between the template DNA strand and the mRNA molecule. Once transcription is complete, the DNA strands and their original coiling are reunited.
The mRNA moves from the cell nucleus to the rough endoplasmic reticulum to initiate protein synthesis in the process known as translation. Thymine does not intervene directly in this, since the mRNA lacks it, taking in its place the pyrimidine base uracil.
Genetic code
Indirectly, thymine is involved, since the base sequence of mRNA is a reflection of that of nuclear DNA.
The sequence of bases can be grouped into triplets of bases known as codons. The codons have the information for the incorporation of the different amino acids to the protein chain being synthesized; this constitutes the genetic code.
The genetic code is formed by 64 triplets of bases constituting the codons; there is at least one codon for each of the amino acids in proteins. Likewise, there are translation initiation codons (AUG) and codons for its termination (UAA, UAG).
In summary, thymine plays a determining role in the process that ends with protein synthesis.
Health implications
Thymine is the target for the action of 5-fluorouracil, a structural analog of this compound. The drug used in cancer treatment is incorporated in the place of thymine into cancer cells, blocking their proliferation.
Ultraviolet light acts on the regions of the DNA bands that contain thymine at neighboring sites, forming thymine dimers. These dimers create "knots" that block the nucleic acid from working.
Initially it is not a problem due to the existence of repair mechanisms, but if these fail, they can cause serious disorders. This appears to be the case for xeroderma pigmentosa, a rare autosomal recessive disease.
References
- Webmaster, Department of Chemistry, University of Maine, Orono. (2018). Structure and Properties of Purines and Pryimidines. Taken from: chemistry.umeche.maine.edu
- Laurence A. Moran. (July 17, 2007). Tautomers of Adenine, Cytosine, Guanine, and Thymine. Taken from: sandwalk.blogspot.com
- Daveryan. (June 6, 2010). Thymine skeletal.. Recovered from: commons.wikimedia.org
- Wikipedia. (2018). Thymine. Taken from: en.wikipedia.org
- Mathews, CK, Van Holde, K. E: and Ahern, KG Biochemistry. 2002. Third edition. Edit. Pearson Adisson Wesley
- O-Chem in Real Life: A 2 + 2 Cycloaddition. Taken from: asu.edu