Thymine: Function & Diseases

Thymine is one of the four nucleic bases that make up DNA strands, the seat of genetic information. The complementary base in the double helix is always adenine. Chemically, it is a heterocyclic aromatic compound with a pyrimidine backbone. In addition to serving as a nucleic base in DNA to encode the amino acid sequence for protein synthesis, thymine plays a role in the body’s metabolism as a component of certain bioactive nucleotides.

What is thymine?

The basic structure of thymine is formed by a heterocyclic aromatic six-membered ring, the pyrimidine backbone. Thymine is one of a total of 4 nucleic bases that make up DNA strands. Strictly speaking, it is the nucleotide of thymine. First, a deoxyribose molecule is added, so that the nucleoside deoxythymidine is formed from the nucleic base. Additional addition of one to three phosphate groups then converts the nucleoside to the nucleotide deoxythymidine monophosphate (dTMP), deoxythymidine diphosphate (dTDP), or deoxythymidine triphosphate (dTTP). Thymine does not normally occur in RNA because thymine is replaced there by the nucleic base uracil. In RNA, uracil is the complementary base to adenine. However, thymine occurs as a special glycoside (ribothymidine) with an attached ribose molecule in transfer RNA (tRNA). The chemical molecular formula C5H5N2O2 shows that thymine is composed exclusively of carbon, hydrogen, nitrogen, and oxygen, substances that are ubiquitous. No rare minerals or trace elements are involved in the composition of thymine. Thymine is preferentially obtained by the body from the metabolism of proteins containing thymine or thymidine. Thymine can be completely broken down by body metabolism to carbon dioxide and water.

Function, effects, and roles

The main function of thymine is to be present in one of the strands of the double helix of DNA at each of the designated sites and to form a bond with the complementary nucleic base adenine via a two-way hydrogen bond. For the fulfillment of its main task, thymine does not intervene directly in the metabolism, but together with the other three nucleic bases determines only by its position on the corresponding section of the double helix strand which amino acids are assembled into proteins and in which order. After making a copy of the corresponding section of a DNA base strand, the so-called messenger RNA (mRNA), this is transferred from the nucleus of the cell into the cytoplasm. In the cytoplasm, the translation of the base sequences into the type and sequence of amino acids, which are assembled into the intended protein via peptide bonds, takes place at the ribosomes. The function and tasks of thymine or deoxythymidine within metabolism are not precisely known. In animal experiments, thymine administration has been shown to improve blood counts in pernicious anemia, anemia caused by B12 deficiency. It is likely that vitamin B12 deficiency can be related to a disturbance in the synthesis of nucleosides.

Formation, occurrence, properties, and optimal levels

The body can synthesize thymine on its own when needed. However, because synthesis is laborious and energy-intensive, the vast majority of the nucleic base is obtained by some form of recycling of spent thymine or thymidine compounds or from the degradation of proteins containing thymine or thymidine. This pathway of synthesis is known as the Salvage Pathway. It is followed whenever it means that the body has to expend less energy on the degradation of higher molecules than on biosynthesis. Thymine forms shiny needle- or prism-shaped crystals that taste bitter and can be dissolved in hot water, but hardly in alcohol or ether. Since the basic structure of thymine consists of a six-membered ring, thymine can occur in six different tautomers, each with the same chemical formula but with a different arrangement of double bonds and/or attached groups or molecules. Since the nucleic base hardly occurs in free form in the organism, there is no optimal level or concentration that could be considered as a reference value for pathological deviations and disorders. On the other hand, thymine serves as a drug base for the production of drugs used for the treatment of certain viral diseases such as AIDS and hepatitis B.

Diseases and disorders

During the creation of copies of DNA strands in the form of the creation of mRNA, errors can occur such as too frequent replication of a triplet, a sequence of three nucleic bases that determine the type of amino acid, or there is a loss of a sequence, or there is a point mutation with potentially serious consequences. Common to all problems arising from the creation of mRNA is that the errors are not caused by the nucleic bases themselves. However, only thymine makes a certain exception because it is susceptible to DNA mutation under the influence of UV light. When two thymine bases are directly adjacent on a DNA strand, under the influence of UV light (sunlight) the methyl groups (CH3 group) can form a stable bond with the respective adjacent thymine, resulting in a dimer that chemically corresponds to a derivative of cyclobutane. The DNA is thus modified at this point so that a shortened version with fewer DNA bases is produced when the DNA strand is replicated. If transcription occurs, the error previously copied from the mRNA is translated into an erroneous amino acid sequence. A modified protein is then produced, which at worst has no biological activity or is unstable and is immediately metabolized again. This is a gene mutation that is predominantly observed in skin cells exposed to direct sunlight. Therefore, experts debate whether such dimers can cause skin cancer.