ADENINE: STRUCTURE, BIOSYNTHESIS, FUNCTIONS - BIOLOGY

The adenine is nucleobase purine type found in ribonucleic acids (RNA) and deoxyribonucleic (DNA) of living organisms and viruses. Some of the functions of these biopolymers (RNA and DNA) are the storage, replication, recombination and transfer of genetic information.

To constitute nucleic acids, first the nitrogen atom 9 of adenine forms a glycosidic bond with the prime carbon 1 (C1 ′) of ribose (of RNA) or 2'-deoxyribose (of DNA). In this way, adenine forms the nucleoside adenosine or adenosine.

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Second, the hydroxyl group (-OH) on the 5 ′ carbon of the sugar (ribose or 2′-deoxyribose), of adenosine, forms an ester bond with a phosphate group.

In living cells, depending on the number of phosphate groups present, it can be adenosine-5′-monophosphate (AMP), adenosine-5′-diphosphate (ADP) and adenosine-5′-triphosphate (ATP). Equivalents possessing 2′-deoxyribose also exist. For example, deoxyadenosine-5′-monophosphate (dAMP), etc.

Structure and characteristics

Adenine, called 6-aminopurine, has the empirical formula C ₅ H ₅ N ₅, and has a molecular weight of 135.13 g / mol, being purified as a pale yellow solid, with a boiling point of 360ºC.

Its molecule has a double ring chemical structure with conjugated double bonds, which is the fusion of a pyrimidine with an imidazole group. Because of this, adenine is a flat heterocyclic molecule.

It has a relative solubility of 0.10 g / mL (at 25 ºC), in acidic and basic aqueous solutions, with a pKa of 4.15 (at 25 ºC).

For this same reason, it is capable of being detected by absorbance at 263 nm (with an absorption coefficient of E ^{1.2 mM} = 13.2 M ^-1.cm ^-1 in 1.0 M HCl), an area of the electromagnetic spectrum corresponding to near ultraviolet.

Biosynthesis

Purine nucleotide biosynthesis is identical in practically all living things. It begins with the transfer of an amino group from glutamine to the substrate 5-phosphoribosyl-1-pyrophosphate (PRPP), and produces 5-phosphoribosylamine (PRA).

This is a reaction catalyzed by glutamine-PRPP transferase, a key enzyme in the regulation of this metabolic pathway.

After sequential additions of the amino acids glutamine, glycine, methenyl-folate, aspartate, N ¹⁰ -formyl-folate to the PRA, which include condensations and ring closure, inosine-5′-monophosphate (IMP) is produced, whose heterocyclic unit is hypoxanthine (6-oxypurine).

These additions are driven by the hydrolysis of ATP to ADP and inorganic phosphate (Pi). Subsequently, an amino group from aspartate is added to the IMP, in a reaction coupled with the hydrolysis of guanosine-triphosphate (GTP), to finally generate AMP.

The latter exercises control of this biosynthetic pathway through negative feedback, acting on the enzymes that catalyze the formation of PRA and the modification of IMP.

As with the breakdown of other nucleotides, the nitrogenous base of adenosine nucleotides goes through a process called "recycling."

Recycling consists of the transfer of a phosphate group from PRPP to adenine, and forms AMP and pyrophosphate (PPi). It is a single step catalyzed by the enzyme adenine phosphoribosyltransferase.

Roles in oxidative and reductive metabolism

Adenine is part of several important molecules in oxidative metabolism, which are the following:

Flavin adenine dinucleotide (FAD / FADH ₂) and nicotinamide adenine dinucleotide (NAD ⁺ / NADH), which participate in oxidation-reduction reactions by transferring hydride ions (: H ^-).
Coenzyme A (CoA), which participates in the activation and transfer of acyl groups.

During oxidative metabolism, NAD ⁺ functions as an electron acceptor substrate (hydride ions) and forms NADH. Whereas FAD is a cofactor that accepts electrons and becomes FADH ₂.

On the other hand, adenine forms nicotinamide adenine dinucleotide phosphate (NADP ⁺ / NADPH), which participates in reductive metabolism. For example, NADPH is an electron donor substrate during lipid and deoxyribonucleotide biosynthesis.

Adenine is part of the vitamins. For example, niacin is the precursor to NAD ⁺ and NADP ⁺ and riboflavin is the precursor to FAD.

Functions in gene expression

Adenine is part of S-adenosylmethionine (SAM), which is a methyl radical donor (-CH ₃) and participates in the methylation of adenine and cytosine residues in prokaryotes and eukaryotes.

In prokaryotes, methylation provides its own DNA recognition system, thereby protecting the DNA from its own restrictive enzymes.

In eukaryotes, methylation determines the expression of genes; that is, it establishes which genes should be expressed and which ones should not. In addition, adenine methylations can mark repair sites for damaged DNA.

Many proteins that bind to DNA, such as transcription factors, have amino acid residues glutamine and asparagine that form hydrogen bonds with the N ⁷ atom of adenine.

Functions in energy metabolism

Adenine is part of ATP, which is a high-energy molecule; that is, its hydrolysis is exergonic, and the Gibbs free energy is a high and negative value (-7.0 Kcal / mol). In cells, ATP participates in many reactions that require energy, such as:

- Promote endergonic chemical reactions catalyzed by enzymes that participate in intermediate metabolism and in anabolism, through the formation of high-energy intermediates or coupled reactions.

- Promote protein biosynthesis in ribosomes, by allowing the esterification of amino acids with their corresponding transfer RNA (tRNA), to form aminoacyl-tRNA.

- Promote the movement of chemical substances through cell membranes. There are four types of carrier proteins: P, F, V, and ABC. The P, F, and V types carry ions and the ABC type carries substrates. For example, the Na ⁺ / K ⁺ ATPase, class P, needs an ATP to pump two K ⁺ into the cell and three Na ^{+ out}.

- Boost muscle contraction. Provides the energy that directs actin filament glide over myosin.

- Promote nuclear transport. When the beta subunit of the heterodimeric receptor binds to ATP, it interacts with components of the nuclear pore complex.

Other functions

Adenosine serves as a ligand for receptor proteins present in neurons and cells of the intestinal epithelium, where it acts as an extracellular or neuromodulator messenger, when changes occur in cellular energy metabolism.

Adenine is present in powerful antiviral agents such as arabinosiladenine (araA), which is produced by some microorganisms. In addition, it is present in puromycin, an antibiotic that inhibits protein biosynthesis and is produced by microorganisms of the genus Streptomyces.

In AMP it serves as a substrate for reactions that generate the second messenger cyclic AMP (cAMP). This compound, produced by the enzyme adenylate cyclase, is essential in most of the intracellular signaling cascades, necessary for cell proliferation and survival, as well as inflammation and cell death.

Sulfate in its free state is not reactive. Once it enters the cell, it is converted to adenosine-5'-phosphosulfate (APS), and subsequently to 3'-phosphoadenosine-5'-phosphosulfate (PAPS). In mammals, PAPS is the donor of sulfate groups and forms organic sulfate esters such as those of heparin and chondroitin.

In cysteine biosynthesis, S-adenosylmethionine (SAM) serves as a precursor for the synthesis of S-adenosylhomocysteine, which is transformed by several steps, catalyzed by enzymes, into cysteine.

Prebiotic synthesis

Experimentally, it has been shown that keeping hydrogen cyanide (HCN) and ammonia (NH ₃) enclosed, under laboratory conditions similar to those that prevailed on early Earth, adenine is produced in the resulting mixture. This occurs without the need for any living cell or cellular material to be present.

Prebiotic conditions include the absence of free molecular oxygen, a highly reducing atmosphere, intense ultraviolet radiation, large electrical arcs such as those generated in storms, and high temperatures. This assumes that adenine was the main and most abundant nitrogen base formed during prebiotic chemistry.

Thus, the synthesis of adenine would constitute a key step that would make the origin of the first cells possible. These had to have a membrane that formed a closed compartment, inside which the molecules required to build the first biological polymers necessary for self-perpetuation would be found.

Use as a therapeutic and cell culture factor

Adenine is, along with other organic and inorganic chemical compounds, an essential ingredient in the recipe used in all biochemistry, genetics, molecular biology and microbiology laboratories in the world, to grow cells that are viable over time.

This is because wild normal cell varieties can detect and capture available adenine from the surrounding environment and use it to synthesize their own adenine nucleosides.

This supposes a form of cellular survival, that economizes internal resources synthesizing more complex biological molecules from simple precursors taken from the outside.

In experimental models of chronic kidney disease, mice have a mutation in the adenine phosphoribosyltransferase gene that produces an inactive enzyme. These mice are administered commercial solutions containing adenine, sodium citrate, and glucose, intravenously, to promote rapid recovery.

This treatment is based on the fact that PRPP, the initial metabolite for purine biosynthesis, is synthesized from ribose-5-phosphate through the pentose phosphate pathway, whose starting metabolite is glucose-6-phosphate. However, many of these solutions are not approved by international regulatory bodies for human use.

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ADENINE: STRUCTURE, BIOSYNTHESIS, FUNCTIONS - BIOLOGY - 2025