Uracil is a nucleic base that forms a base pair with adenine in RNA and is the counterpart to the similarly structured thymine in DNA. Uracil represents an aromatic, heterocyclic compound with a six-membered ring consisting of a modified pyrimidine backbone. In RNA, uracil is present in the form of uridine, which is a nucleoside linked to a ribose molecule by an n-glycosidic bond and, like thymine, forms two hydrogen bonds with the complementary base adenine.
What is uracil?
Uracil is one of four nucleic bases that make up the RNA strands of the genetic material. Here, uracil replaces the similarly composed nucleic base thymine of DNA. Uracil is a heterocyclic, aromatic compound with a modified pyrimidine six-membered ring as its basic structure. In RNA, uracil exists as a nucleoside called uridine. Uridine, like thymidine in DNA, forms two hydrogen bonds with the complementary base adenine. The chemical formula C4H4N2O2 shows that uridine consists exclusively of carbon, hydrogen, nitrogen and oxygen. No rare minerals or trace elements are required for biosynthesis. As with the other nucleic bases that make up uridine, the body is capable of synthesizing uridine, but prefers to obtain uridine from recycling processes and from the degradation of certain proteins that contain uridine in its pure form or in the nucleoside form as uridine, or even in the phosphorylated form of uridine. Uridine can be phosphorylated with one to three phosphate groups to form uridine mono- (UMP), uridine di- (UDP) or uridine triphosphate (UTP). In the body, uridine occurs mainly as a component of RNA or in the phsphorylated form of uridine.
Function, effects, and roles
The main function of uracil is to occupy its respective positions at designated sites in the base strands of RNA and to bond with the complementary nucleic base adenine via a two-way hydrogen bond during the transcription or translation phase. This is one of several prerequisites for the corresponding RNA base strand to be properly encoded and, after complementary copying by so-called messenger RNA (mRNA), to lead to the synthesis of the genetically intended proteins in terms of amino acid selection and sequence. Proteins consist of a string of certain proteinogenic amino acids linked together by peptide bonds. Structurally, they are polypeptides, which are called proteins or albumen from a number of one hundred or more amino acids involved. This means, in effect, that the main role of uracil or uridine – like that of the other nucleic bases – is a passive one. Uracil is not actively involved in biochemical conversion processes. A possible role of uridine or uridine phosphorylated with one to three phosphate groups as a component of enzymes or hormones is not known.
Formation, occurrence, properties, and optimal values
In principle, the body is able to synthesize uracil itself. No rare basic substances are required. However, synthesis is complex and requires high energy expenditure, so the body prefers to obtain uracil and uridine by catalytic means, via the degradation and remodeling of other substances containing a pyrimidine backbone. This particular pathway of procuring uracil, which the body also prefers in the bioactive production of the other nucleic acids, is called the Salvage Pathway. The term translates loosely as recycling and recovery. Since the basic skeleton of uracil consists of a heterocyclic six-membered ring, six different tautomers are possible, each differing by the arrangement of molecules or molecular groups on the six-membered ring. In the dioxo form with two oxygen atoms and no OH group, uracil forms a white powder that only melts at a temperature of 341 degrees Celsius. The significance of the individual tautomers within metabolism is not known. The nucleic base does not occur in free form in the body, but only in bound, phosphorylated, form or as a component of RNA. An optimal concentration of uracil or uridine or a reference value for the definition of a normal range does not exist.Since uracil consists solely of carbon, oxygen, and hydrogen, the body can completely degrade the compound to carbon dioxide, ammonium ions, and oxopropanoic acid and dispose of it without leaving any residue, or use the freed molecular groups to build other substances.
Diseases and disorders
One of the main hazards associated with uracil as an integral component of RNA is the defective preparation of copies of DNA or RNA strands, which leads to the defective synthesis of the intended proteins in subsequent steps. Due to incorrect repeat sequences of certain nucleic acid triplets, omission or other errors, unintended amino acids and/or amino acids in the wrong sequence are strung together via peptide bonds. If the body cannot correct the errors via its own repair capabilities, biochemically inactive proteins or unstable compounds are then formed, which are directly degraded and metabolized by the body. Such defects, however, are not due to active intervention of the nucleic bases. Uracil is important as a basic substance for a drug combination with Tegafur, a cytostatic drug for the treatment of colorectal cancer. Uracil supports the effect of the cytostatic drug because it inhibits its degradation, thereby prolonging the exposure time of the cytostatic drug. In other drug combinations, uracil derivatives such as 5-fluoro-uracil and deoxyuridine are used as inhibitors of folic acid metabolism in advanced colorectal cancer. Cytostatic drugs inhibit the growth and proliferation of cells, but not only the proliferation of certain cancer cells but also the cells of healthy tissues, so undesirable side effects are a challenge in their use.
