Nucleic Bases: Function & Diseases

Nucleic bases are the building blocks that, in their phosphorylated nucleotide form, make up the long chains of DNA and RNA molecules. In DNA, which forms rope ladder-like double strands, the 4 occurring nucleic bases form tight pairings with the respective complementary base via hydrogen bonds. The nucleic bases consist of either a bicyclic purine or a monocyclic pyrimidine backbone.

What are nucleic bases?

The 4 nucleic bases, adenine, guanine, cytosine, and thymine, are the building blocks of DNA’s long double-helix molecular chains, forming the ever-constant pairings adenine-thymine (A-T) and guanine-cytosine (G-C). The two bases adenine and guanine each consist of a modified bicyclic six- and five-membered ring of the purine backbone and are therefore also called purine bases. The basic structure of the other two nucleic bases, cytosine and thymine, consist of a heterocyclic aromatic six-membered ring corresponding to a modified pyrimidine backbone, which is why they are also referred to as pyrimidine bases. Since RNA is mostly present as single strands, there is initially no base pairing there. This only takes place during replication via the mRNA (messenger RNA). The copy of the RNA strand consists of the complementary nucleic bases analogous to the second strand of DNA. The only difference is that thymine in RNA is substituted by uracil. The DNA and RNA chain molecules are not formed by the nucleic bases in pure form, but they first combine in the case of DNA with the 5-sugar deoxyribose to form the corresponding nucleoside. In the case of RNA, the sugar group consists of ribose. In addition, the nucleosides are phosphorylated with a phosphate residue to form so-called nucleotides. The purine bases hypoxanthine and xanthine, which also occur in DNA and RNA, correspond to modified thymine. Hypoxanthine is formed from adenine by replacing the amino group (-NH3) with a hydroxy group (-OH), and xanthine is formed from guanine. Neither nucleic base contributes to the transmission of genetic information.

Function, action, and roles

One of the most important functions of the nucleic bases that make up the double strands of DNA is to provide a presence at their respective designated positions. The sequence of nucleic bases corresponds to the genetic code and defines the type and sequence of amino acids that make up proteins. This means that the most important function of nucleic bases as a component of DNA consists of a passive, static, role, i.e. they do not actively intervene in metabolism and their biochemical structure is not changed during the reading process by messenger RNA (mRNA). This partly explains the longevity of DNA. The half-life of mitochondrial DNA (mtDNA), at which half of the bonds originally present between the nucleic bases break down, is highly dependent on environmental conditions and varies from about 520 years in average conditions with positive temperatures to up to 150,000 years in permafrost conditions. As a component of RNA, nucleic bases have a somewhat more active role. In principle, when cells divide, the DNA double strands are broken and separated from each other to form a complementary strand, mRNA, which is the working copy, so to speak, of the genetic material and serves as the basis for the selection and sequence of amino acids from which the intended proteins are assembled. Another nucleic base, dihydrouracil, is found only in the so-called transport RNA (tRNA), for amino acid transport during protein synthesis. Some nucleic bases fulfill a completely different function as part of enzymes, which actively enable and control certain biochemical processes by catalytic means. The best-known function is performed by adenine as a nucleotide in the energy balance of cells. Here, adenine performs an important role as an electron donor as adenosine diphosphate (ADP) and adenosine triphosphate (ATP), and as a component of nicotinamide adenine dinucleotide (NAD).

Formation, occurrence, properties, and optimal levels

In the nonphosphorylated form, nucleic bases consist exclusively of carbon, hydrogen, and oxygen, substances that are ubiquitous and freely available. Therefore, the body is capable of synthesizing nucleic bases on its own, but the process is complex and energy-consuming. Therefore, the recovery of nucleic acids by recycling is preferred, e. g.B. by the degradation of proteins containing certain compounds that can be isolated and converted into nucleic acids with little or even energy gain. As a rule, nucleic acids do not occur in pure form in the body, but mostly as a nucleoside or deoxynucleoside with an attached ribose or deoxyribose molecule. As a component of DNA and RNA and as a component of certain enzymes, the nucleic acids or their nucleosides are additionally reversibly phosphorylated with one to three phosphate groups (PO4-). A reference value for an optimal supply of nucleic bases does not exist. A deficiency or excess of nucleic bases can only be determined indirectly via certain disturbances in metabolism.

Diseases and disorders

The type of hazards, disorders, and risks that are associated with nucleic bases are errors in number and sequence on DNA or RNA strands, resulting in a change in coding for protein synthesis. If the body cannot correct the error via its repair mechanisms, synthesis of biologically inactive or usable proteins occurs, which in turn can lead to mild to severe metabolic disorders. For example, gene mutations may be present that can trigger symptomatic diseases from the outset via metabolic disorders, which may be incurable. But even in a healthy genome, copying errors can occur in the replication of DNA and RNA chains, which have an effect on metabolism. A known metabolic disorder in purine balance, for example, is due to a gene defect on the x chromosome. Because of the gene defect, the purine bases hypoxantine and guanine cannot be recycled, which ultimately promotes the formation of urinary stones and, in the joints, gout.