The cadaverine is a naturally occurring polyamine with multiple bioactive forms. Polyamines are molecules with cationic characteristics that are distributed throughout the cell cytosol and help regulate cell growth and differentiation processes.
In animals, increases in the concentration of cadaverine in the cytosol of cells have generally been related to cell growth. However, on occasion, such growth may be due to tumorigenesis of the tissue.
Graphic diagram of a cadaverine molecule (Source: Calvero. Via Wikimedia Commons)
In plants, cadaverine has been shown to play an essential role in cell division and embryogenesis. It interacts directly with nucleic acids and anionic components that the plant cell membrane possesses.
Cadaverine is easily synthesized from one of the basic amino acids, rich in nitrogen groups, such as alanine. Because of this, foods rich in amino acids, if not properly preserved, develop rotten odors as a result of the formation of cadaverine.
Today, cadaverine is produced with commercial interest through direct microbial fermentation or whole cell bioreactors.
For all these reasons, cadaverine has a large number of applications for biotechnology in the areas of agriculture and medicine and, at present, this compound is becoming an important industrial chemical, due to its wide variety of applications.
Structure
Cadaverine has a nucleus made up of an α-alkane composed of 5 carbon atoms arranged in a linear fashion (pentane) and that at its ends (carbons 1 and 5) has two amines (ω-diamine). Its structure is very similar to that of hexamethylenediamine and, therefore, it is used in the synthesis of polyamides and polyurethanes.
The common name "cadaverina" comes from the scent of decomposing corpses. Bacteria that begin to decompose bodies synthesize a large amount of cadaverine and cause that foul aroma.
The molecular formula of cadaverine is C5H14N2 and the name of the chemical compound can be 1,5-pentanediamine or 1,5-diaminopentane. It is a compound soluble in water.
The molecular weight of cadaverine is 102.178 g / mol, it has a melting point of 9 ° C and a boiling point of 179 ° C. The compound is flammable in the presence of a heat source above 62 ° C.
In its commercial form, cadaverine is in a colorless liquid state with the repellent and unpleasant odor characteristic of the compound.
This compound is homologous to putrescine, however, putrescine has a central skeleton of four carbon atoms (butane) and not five, like cadaverine.
Most compounds with a structure similar to cadaverine, such as putrescine, norespimidine, spermidine, and spermine, are characterized by their strong odor, typically recognized as a foul odor characteristic of decaying meat.
Features
In bacteria
In bacteria, one of the main functions of cadaverine is to regulate the pH in the cytosol, that is, it protects cells against acidic stress and achieves this when the pH decreases and there are abundant amounts of L-lysine in the medium, from which they can synthesize cadaverine.
This protection mechanism is activated by the signaling of membrane proteins called cadaverine C. These are activated when they detect an increase in the concentration of H + ions outside the cell.
Furthermore, when cells are in anaerobic conditions (absence of oxygen) it protects them from the absence of inorganic phosphorus (Pi).
In anaerobic bacteria, cadaverine is an essential component of the cell wall, since it functions as a bond between peptidoglycan and the outer membrane. Cadaverine also participates in the biosynthesis and export of siderophores to the extracellular medium.
In plants
In plants the application of cadaverine and its derivatives as a modulator of stress and senescence has been studied. This intervenes in the signal system to activate the defense systems against both factors.
Some scientists propose that cadaverine binds to the sugar phosphate backbone of DNA, protecting it and making it more stable against mutagenic agents, as high concentrations have been found in plant cells under osmotic and saline stress.
The addition of cadaverine to frozen plant tissues decreases DNA damage, increases the production of antioxidant enzymes and mRNA. An increase in the concentration of cadaverine has been detected in cells infected by pathogens.
However, there are still many controversies about the exact activity of cadaverine in the immune response of plants. In general terms, cadaverine is considered as a conductor and signal transducer in the internal metabolism of plants.
In animals
Little is known about the mechanism of action of cadaverine in animals. However, it is clear that it is not synthesized in the cytosol, since animal cells do not have the enzyme necessary for this reaction.
This compound is formed within the cell through different routes. The presence of cadaverine has always been found in growing animal cells, whether they show normal or excessive growth (due to some pathology).
Synthesis
In almost all organisms, cadaverine is produced by direct decarboxylation of the amino acid L-alanine, thanks to the action of the enzyme lysine decarboxylase inside their cells.
Graphic scheme of the synthesis of cadavaerin by the action of the enzyme lysine decarboxylase (LDC) (Source: RicHard-59 Via Wikimedia Commons
In plants, the enzyme lysine decarboxylase is found inside chloroplasts. Specifically in the stroma and in the shoots of the seeds (seedlings) an increase in the production of cadaverine has been found.
However, seeds, embryonic axis, cotyledons, epicotyl, hypocotyl, and roots show the highest peaks of activity of the enzyme lysine decarboxylase in many plant species.
Despite the above, there is, in fact, an information gap on the experimental production of cadaverine by direct enzymatic catalysis, since lysine decarboxylase loses 50% of its activity after producing a certain amount of cadaverine.
At an industrial level, this compound is obtained by separation and purification methods from bacteria maintained in bioreactors, which is achieved using organic solvents such as n-butanol, 2-butanol, 2-octanol or cyclohexanol.
Another method by which a good yield is obtained in obtaining cadaverine is the separation of phases by chromatography, distillation or precipitation, since it has a lower melting point than many of the other compounds in cell fermentation.
References
- Gamarnik, A., & Frydman, RB (1991). Cadaverine, an essential diamine for the normal root development of germinating soybean (Glycine max) seeds. Plant physiology, 97 (2), 778-785.
- Kovács, T., Mikó, E., Vida, A., Sebő, É., Toth, J., Csonka, T.,… & Tóth, D. (2019). Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors. Scientific reports, 9 (1), 1300.
- Ma, W., Chen, K., Li, Y., Hao, N., Wang, X., & Ouyang, P. (2017). Advances in cadaverine bacterial production and its applications. Engineering, 3 (3), 308-317.
- Samartzidou, H., Mehrazin, M., Xu, Z., Benedik, MJ, & Delcour, AH (2003). Cadaverine inhibition of porin plays a role in cell survival at acidic pH. Journal of bacteriology, 185 (1), 13-19.
- Tomar, PC, Lakra, N., & Mishra, SN (2013). Cadaverine: a lysine catabolite involved in plant growth and development. Plant signaling & behavior, 8 (10), e25850.