Spermidine is a

polyamine A polyamine is an organic compound having two or more amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. ...

compound () found in

ribosome Ribosomes () are molecular machine, macromolecular machines, found within all cell (biology), cells, that perform Translation (biology), biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order s ...

s and living tissues and having various metabolic functions within organisms.

Function

Spermidine is an

aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated (in which all ...

polyamine.

Spermidine synthase Spermidine synthase is an enzyme () that catalyzes the transfer of the propylamine group from ''S''-adenosylmethioninamine to putrescine in the biosynthesis of spermidine. The systematic name is S-adenosyl 3-(methylthio)propylamine:putrescine 3- ...

(SPDS) catalyzes its formation from

putrescine Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of Putrefaction, putref ...

. It is a precursor to other polyamines, such as

spermine Spermine is a polyamine involved in cellular metabolism that is found in all eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some bacteria as well. It is found as a p ...

and its structural

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

thermospermine. Spermidine synchronizes an array of biological processes, (such as Ca²⁺, Na⁺, K⁺ -ATPase) thus maintaining membrane potential and controlling intracellular pH and volume. Spermidine regulates biological processes, such as Ca²⁺ influx by glutamatergic ''N''-methyl-D-aspartate receptor (NMDA receptor), which has been associated with nitric oxide synthase (NOS) and cGMP/PKG pathway activation and a decrease of Na⁺,K⁺-ATPase activity in cerebral cortex synaptosomes. Polyamine synthesis

Spermidine is a

longevity Longevity may refer to especially long-lived members of a population, whereas ''life expectancy'' is defined Statistics, statistically as the average number of years remaining at a given age. For example, a population's life expectancy at birth ...

agent in mammals due to various mechanisms of action, which are just beginning to be understood.

Autophagy Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-depe ...

is the main mechanism at the molecular level, but evidence has been found for other mechanisms, including inflammation reduction, lipid metabolism, and regulation of cell growth, proliferation, and death. Spermidine has been theorized to promote autophagy via the MAPK pathway by inhibiting phosphorylation of raf, or possibly by inhibiting cytosolic autophagy-related protein acetylation by

EP300 Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the ''EP300'' gene. It functions as histone ace ...

and thereby increasing acetylation of

tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...

. Spermidine is known to regulate plant growth, assisting the ''in vitro'' process of transcribing RNA, and inhibition of NOS. Also, spermidine is a precursor to other polyamines, such as spermine and thermospermine, some of which contribute to tolerance against

drought A drought is a period of drier-than-normal conditions.Douville, H., K. Raghavan, J. Renwick, R.P. Allan, P.A. Arias, M. Barlow, R. Cerezo-Mota, A. Cherchi, T.Y. Gan, J. Gergis, D. Jiang, A. Khan, W. Pokam Mba, D. Rosenfeld, J. Tierney, ...

and

salinity Salinity () is the saltiness or amount of salt (chemistry), salt dissolved in a body of water, called saline water (see also soil salinity). It is usually measured in g/L or g/kg (grams of salt per liter/kilogram of water; the latter is dimensio ...

in plants. Spermidine has been tested and discovered to encourage hair shaft elongation and lengthen hair growth. Spermidine has also been found to “upregulate expression of the epithelial stem cell-associated keratins K15 and K19, and dose-dependently modulated K15 promoter activity ''in situ'' and the colony forming efficiency, proliferation and K15 expression of isolated human K15-GFP+ cells ''in vitro''.”

Biochemical actions

Spermidine's known actions include: * Inhibits neuronal nitric oxide synthase (nNOS) * Binds and precipitates DNA * Polyamine plant growth regulator

Sources

Good dietary sources of spermidine are aged cheese, mushrooms, soy products, legumes, corn, and whole grains. Spermidine is plentiful in a

Mediterranean diet The Mediterranean diet is a concept first proposed in 1975 by the American biologist Ancel Keys and chemist Margaret Keys. The diet took inspiration from the eating habits and traditional food typical of Crete, much of the rest of Greece, and s ...

. For comparison: The spermidine content in human seminal plasma varies between approx. 15 and 50 mg/L (mean 31 mg/L). Note: spermidine content varies by source and age. See ref for details. In grains, the

endosperm The endosperm is a tissue produced inside the seeds of most of the flowering plants following double fertilization. It is triploid (meaning three chromosome sets per nucleus) in most species, which may be auxin-driven. It surrounds the Embryo#Pla ...

contains most of the spermidine. One of the best known grain dietary sources is

wheat germ The germ of a cereal grain is the part that develops into a plant; it is the seed embryo. Along with bran, germ is often a by-product of the milling that produces refined grain products. Cereal grains and their components, such as wheat germ ...

, containing as much as 243 mg/kg.

Uses

* Spermidine can be used in

electroporation Electroporation, also known as electropermeabilization, is a microbiological and biotechnological technique in which an electric field is applied to cells to briefly increase the permeability of the cell membrane. The application of a high-vo ...

while transferring the DNA into the cell under the electrical impulse. May be used for purification of DNA-binding proteins. * Spermidine is also used, along with calcium chloride, for precipitating DNA onto microprojectiles for bombardment with a

gene gun In genetic engineering, a gene gun or biolistic particle delivery system is a device used to deliver exogenous DNA (transgenes), RNA, or protein to cells. By coating particles of a heavy metal with a gene of interest and firing these micro-projec ...

. * Spermidine has also been reported to protect the heart from aging and prolong the lifespan of mice, while in humans it was correlated with lower blood pressure. It also was found to reduce the amount of aging in yeast, flies, worms, and human immune cells by inducing

autophagy Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-depe ...

. * Spermidine may play a role in male and female fertility. Fertile men have higher spermidine levels than men who are infertile, and spermidine supplementation has been shown to help maintain a healthy hormone balance and reduce oxidative stress. * Spermidine is commonly used for in vitro molecular biology reactions, particularly, in vitro transcription by phage RNA polymerases, ''in vitro'' transcription by human RNA polymerase II, and ''in vitro'' translation. *Spermidine increases specificity and reproducibility of Taq-mediated PCR by neutralizing and stabilizing the negative charge on DNA phosphate backbone.

References

External links