Рибонуклеотиды: структура, функции и роль в биохимии.

Nucleotide containing ribose as its pentose component
In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic monomeric building blocks for RNA. Deoxyribonucleotides, formed by reducing ribonucleotides with the enzyme ribonucleotide reductase (RNR), are essential building blocks for DNA. There are several differences between DNA deoxyribonucleotides and RNA ribonucleotides. Successive nucleotides are linked together via phosphodiester bonds. Ribonucleotides are also utilized in other cellular functions. These special monomers are utilized in both cell regulation and cell signaling as seen in adenosine monophosphate (AMP). Furthermore, ribonucleotides can be converted to adenosine triphosphate (ATP), the energy currency in organisms. Ribonucleotides can be converted to cyclic adenosine monophosphate (cyclic AMP) to regulate hormones in organisms as well. Both types of pentoses in DNA and RNA are in their β furanose (closed five membered ring) form and they define the identity of a nucleic acid. DNA is defined by containing 2' deoxy ribose nucleic acid while RNA is defined by containing ribose nucleic acid. Nucleotides with phosphate groups in positions other than on the 5' carbon have also been observed. Examples include ribonucleoside 2',3' cyclic monophosphates which are isolatable intermediates, and ribonucleoside 3' monophosphates which are end products of the hydrolysis of RNA by certain ribonucleases. Other variations include adenosine 3',5' cyclic monophosphate (cAMP) and guanosine 3',5' cyclic monophosphate (cGMP).

Ribonucleotides are linked together to form RNA strands via phosphodiester bonds. The 5' phosphate group of one nucleotide is linked to the 3' hydroxyl group of the next nucleotide, creating a backbone of alternating phosphate and pentose residues. There is no phosphodiester bond at each end of the polynucleotide. Phosphodiester bonds are formed between ribonucleotides by the enzyme RNA polymerase. The RNA chain is synthesized from the 5' end to the 3' end as the 3' hydroxyl group of the last ribonucleotide in the chain acts as a nucleophile and launches a hydrophilic attack on the 5' triphosphate of the incoming ribonucleotide, releasing pyrophosphate as a by product. Due to the physical properties of the nucleotides, the backbone of RNA is very hydrophilic and polar. At neutral pH, nucleic acids are highly charged as each phosphate group carries a negative charge. Both DNA and RNA are built from nucleoside phosphates, also known as mononucleotide monomers, which are thermodynamically less likely to combine than amino acids. Phosphodiester bonds, when hydrolyzed, release a considerable amount of free energy. Therefore, nucleic acids tend to spontaneously hydrolyze into mononucleotides. The precursors for RNA are GTP, CTP, UTP and ATP, which is a major source of energy in group transfer reactions.

During DNA synthesis, DNA polymerases must select against ribonucleotides, present at much higher levels compared with deoxyribonucleotides. It is crucial that there is selectivity as DNA replication has to be accurate to maintain the organism's genome. It has been shown that the active sites of Y family DNA polymerases are responsible for maintaining a high selectivity against ribonucleotides. Most DNA polymerases are also equipped to exclude ribonucleotides from their active site through a bulky side chain residue that can sterically block the 2' hydroxyl group of the ribose ring. However, many nuclear replicative and repair DNA polymerases incorporate ribonucleotides into DNA, suggesting that the exclusion mechanism is not perfect.

Prior to James Watson and Francis Crick's landmark paper that detailed the structure of DNA from Rosalind Franklin's X ray crystallography image, there were several historical scientists that also contributed to its discovery. Friedrich Miescher, a Swiss physician, who, in 1869, was first to isolate and identify nucleic substance from the nuclei of white blood cells he later called “nuclein”, paving the way for the discovery of DNA. Following Mieschers work, was the German biochemist, Albrecht Kossel, who, in 1878, isolated the non protein components of “nuclein”, and discovered the five nucleobases present in nucleic acids: adenine, cytosine, guanine, thymine and uracil. Although some fundamental facts were known about nucleic acids due to these early discoveries, its structure and function remained a mystery. It wasn't until the discovery of nucleotides in 1919 by Phoebus Levene, a Russian Lithuanian biochemist that re opened the gates of the DNA discovery. Levene first identified the carbohydrate component present in yeast RNA was in fact ribose. However, it was not until his discovery that the carbohydrate component in thymus nucleic acid was also a sugar but lacked one oxygen atom, termed deoxyribose, that his discovery was widely appreciated by the scientific community. Eventually, Levene was able to identify the correct order of which the components of RNA and DNA are put together, a phosphate sugar base unit, in which he later called a nucleotide. Although the order of nucleotide components were well understood by Levene, the structure of nucleotide arrangement in space and its genetic code still remained a mystery during the early years of his career.