Cytidine: Function & Diseases

Cytidine belongs to the nucleosides and is composed of the nucleic base cytosine and the sugar ribose. It forms a base pair with guanosine via hydrogen bonding. It also plays a central role in pyrimidine metabolism.

What is cytidine?

Cytidine represents a nucleoside composed of cytosine and ribose. The nitrogen base cytosine is involved in the assembly of nucleic acids along with adenine, guanine, and thymine. Phosphorylation of cytidine results in cytidine monophosphate (CMP), cytidine diphosphate (CDP) or cytidine triphosphate (CTP). Cytidine monophosphate is a nucleotide of RNA. Two purine and two pyrimidine bases are involved in the assembly of each nucleic acid, with thymine exchanged for uracil in RNA. Thus, adenine and guanine belong to the purine bases, while thymine, cytosine and uracil belong to the pyrimidine bases. Cytidine can be deaminated to uridine by cytidine deaminase. Uridine is a nucleoside of ribose and uracil. It can also be phosphorylated to uridine monophosphate. Uridine monophosphate is also an important nucleotide for RNA. Furthermore, CDP and CTP are also activating groups for the synthesis of lecithin, cephalin and cardiolipin. Pure cytidine exists as a water-soluble solid, which decomposes at 201 to 220 degrees. It can be catalytically degraded to cytosine and ribose by the enzyme pyrimidine nucleosidase.

Function, action, and roles

Cytidine plays a central role in pyrimidine metabolism. Pyrimidine provides the backbone for the pyrimidine bases cytosine, thymine, and uracil found in nucleic acids. Thymine is exchanged for uracil in RNA. However, uracil is also formed by the deamination of cytidine with cytidine deaminase. The chemical transformations of the three pyrimidine bases among each other are of central importance for the repair processes in DNA and epigenetic changes. In the context of epigenetics, modifications of various properties do occur as a result of environmental influences. However, the genetic material does not change in the process. Modification changes of an organism are caused by the different expression of genes. Thus, differentiation processes of body cells to form different cell lineages and organs also represent an epigenetic process. Depending on the cell type, different genes are activated or deactivated. This occurs through the methylation of cytidine bases within DNA. Methylation produces methylcytosine, which can be converted to thymine by deamination. The complementary nucleic base guanine in the opposite double strand allows the error to be detected and thymine to be exchanged back to cytosine. However, guanine can also be exchanged for adenine, resulting in a point mutation. If the unmethylated cytosine is deaminated, uracil is formed. Since uracil does not occur in DNA, it is immediately replaced again by cytosine. At the site of cytosine, the mutation rate is somewhat increased by methylation. At the same time, however, more and more genes are switched off by methylations, resulting in further specialization of the cells within the cell line. In repair processes, repair enzymes target the original DNA strand, which they recognize by a higher degree of methylation. Based on the information stored there, the complementary strand is also built. Errors in incorporation are corrected immediately. Furthermore, the enzyme AID (Activation Induced Cytidine Deaminase) very specifically catalyzes the deamination of cytidine groups to uridine groups in single-stranded DNA. Somatic hypermutations occur, which alter the antibody sequences of B cells. Thereafter, selection of the appropriate B cells takes place. Thus, a flexible immune response is possible.

Formation, occurrence, properties, and optimal levels

Cytidine is an intermediate of pyrimidine metabolism. As an isolated compound, it plays no role. As mentioned earlier, it is composed of the nucleic base cytosine and the pentosugar ribose. Cytosine can be synthesized by the body itself. However, its synthesis is very energy-intensive, so it is recovered from nucleic acid building blocks as part of the salvage pathway and can be reincorporated into nucleic acids. Complete degradation of the base produces carbon dioxide, water, and urea. As a nucleoside, it is present in RNA. In DNA, cytosine is bound to deoxyribose, so that the nucleoside deoxycytidine is present here as a building block.

Diseases and disorders

Methylations at cytidine residues of DNA are very important for markers to separate different biochemical processes. However, errors can also occur during methylation that lead to disease. In the case of faulty methylations, both increased and decreased gene activities can be triggered, which do not correspond to the requirements. During cell division, these methylation patterns are inherited. In the long term, changes occur that can lead to disease. For example, some tumor cells have deviating methylation structures that do not occur in healthy cells. Thus, methylation can block certain genes that encode growth-regulating enzymes. If these enzymes are missing, uninhibited cell growth can occur. This also affects enzymes that initiate ordered cell death (apoptosis) when cell defects occur. Targeted manipulation of DNA methylation is not yet possible today. However, there are studies on the complete demethylation of tumor cells to bring them back under the control of growth-regulating proteins. According to several clinical studies, tumor growth could be limited by demethylation in patients with acute myeloid leukemia. This procedure is also known as epigenetic therapy. Methylation processes may also play a role in other diseases. Environmental influences cause the organism to adapt to changed conditions, forming biological modifications based on methylations of the cytidine residues of DNA. Thus, the body performs a learning process, which, however, can also cause misregulation.