Spermidine

Spermidine

Skeletal formula of spermidine
Ball and stick model of spermidine
Names
Preferred IUPAC name N1-(3-Aminopropyl)butane-1,4-diamine
Identifiers
CAS Number	124-20-9 (free base) Y 334-50-9 (trihydrochloride) Y
3D model (JSmol)	Interactive image
Beilstein Reference	1698591
ChEBI	CHEBI:16610  N
ChEMBL	ChEMBL19612  N
ChemSpider	1071  N
DrugBank	DB03566  Y
ECHA InfoCard	100.004.264
EC Number	204-689-0
Gmelin Reference	454510
IUPHAR/BPS	2390
KEGG	C00315  N
MeSH	Spermidine
PubChem CID	1102
RTECS number	EJ7000000
UNII	U87FK77H25  (free base) Y 1O14BED398  (trihydrochloride) Y
UN number	2735
CompTox Dashboard (EPA)	DTXSID4036645
InChI InChI=1S/C7H19N3/c8-4-1-2-6-10-7-3-5-9/h10H,1-9H2 N Key: ATHGHQPFGPMSJY-UHFFFAOYSA-N N
SMILES NCCCCNCCCN
Properties
Chemical formula	C7H19N3
Molar mass	145.250 g·mol−1
Appearance	Colourless liquid
Odor	Fishy, ammoniacal
Density	925 mg mL−1
Melting point	22 to 25 °C (72 to 77 °F; 295 to 298 K)
Solubility in water	145 g L−1 (at 20 °C)
log P	−0.504
UV-vis (λmax)	260 nm
Absorbance	0.1
Refractive index (nD)	1.479
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H314
Precautionary statements	P280, P305+P351+P338, P310
Flash point	112 °C (234 °F; 385 K)
Related compounds
Related amines	Dipropylamine Methyl-n-amylnitrosamine Norspermidine Dibutylamine Iproheptine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N  verify  (what is  YN ?) Infobox references

Spermidine is a polyamine compound (C
_⁷H
_¹⁹N
_³) found in ribosomes and living tissues and having various metabolic functions within organisms.

Function

Spermidine is an aliphatic polyamine. Spermidine synthase (SPDS) catalyzes its formation from putrescine. It is a precursor to other polyamines, such as spermine and its structural isomer 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.

Biosynthesis of spermidine and spermine from putrescine. Ado = 5'-adenosyl.

Spermidine is a longevity agent in mammals due to various mechanisms of action, which are just beginning to be understood. Autophagy 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. ^{[1] [2]} Spermidine has been theorized to promote autophagy via the MAPK pathway by inhibiting phosphorylation of raf, ^[1] or possibly by inhibiting cytosolic autophagy-related protein acetylation by EP300 and thereby increasing acetylation of tubulin. ^[2]

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 and salinity 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.” ^[3]

Biochemical actions

Spermidine's known actions include:

• Inhibits neuronal nitric oxide synthase (nNOS) ^[4]
• Binds and precipitates DNA ^[5]
• Polyamine plant growth regulator ^{[6] [7] [8] [9] [10] [11] [12]}

Sources

Good dietary sources of spermidine are aged cheese, mushrooms, soy products, legumes, corn, and whole grains. ^[13] Spermidine is plentiful in a Mediterranean diet. ^[2] For comparison: The spermidine content in human seminal plasma varies between approx. 15 and 50 mg/L (mean 31 mg/L). ^[14]

Food	Spermidine mg/kg	notes & refs
Wheat germ	243	[15]
Soybean, dried	207	Japanese [13]
Cheddar, 1yr old	199	[13]
Soybean, dried	128	German [13]
Mushroom	89	Japanese [13]
Rice bran	50	[13]
Chicken liver	48	[13]
Green peas	46	[13]
Mango	30	[13]
Chickpea	29	[13]
Cauliflower (cooked)	25	[13]
Broccoli (cooked)	25	[13]

Note: spermidine content varies by source and age. See ref for details.

In grains, the endosperm contains most of the spermidine. One of the best known grain dietary sources is wheat germ, containing as much as 243 mg/kg. ^[15]

Uses

• Spermidine can be used in electroporation 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. ^[16]
• 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. ^[17] It also was found to reduce the amount of aging in yeast, flies, worms, and human immune cells by inducing autophagy. ^[18]
• Spermidine may play a role in male and female fertility. ^[19] Fertile men have higher spermidine levels than men who are infertile, ^[20] and spermidine supplementation has been shown to help maintain a healthy hormone balance and reduce oxidative stress. ^[21]
• Spermidine is commonly used for in vitro molecular biology reactions, particularly, in vitro transcription by phage RNA polymerases, ^[22] in vitro transcription by human RNA polymerase II, ^[23] and in vitro translation.
• Spermidine increases specificity and reproducibility of Taq-mediated PCR by neutralizing and stabilizing the negative charge on DNA phosphate backbone.

See also

• Food portal

• Norspermidine  – chemical compoundPages displaying wikidata descriptions as a fallback
• Putrescine  – Foul-smelling organic chemical compound
• Spermine  – Polyamine involved in cellular metabolism

References

1. Minois N (28 January 2014). "Molecular Basis of the "Anti-Aging" Effect of Spermidine and Other Natural Polyamines – A Mini-Review". Gerontology . 60 (4): 319–326. doi: 10.1159/000356748 . PMID   24481223.
2. Madeo F, Eisenberg T, Pietrocola F, Kroemer G (2018). "Spermidine in health and disease". Science . 359 (6374): eaan2788. doi: 10.1126/science.aan2788 . PMID   29371440.
3. Ramot Y, Tiede S, Bíró T, Abu Bakar MH, Sugawara K, Philpott MP, Harrison W, Pietilä M, Paus R (27 July 2011). "Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell Functions". PLOS ONE. 6 (7): e22564. Bibcode:2011PLoSO...622564R. doi: 10.1371/journal.pone.0022564 . ISSN   1932-6203. PMC   3144892 . PMID   21818338.
4. Hu J, Mahmoud MI, El-Fakahany EE (1994). "Polyamines inhibit nitric oxide synthase in rat cerebellum". Neuroscience Letters. 175 (1–2): 41–5. doi:10.1016/0304-3940(94)91073-1. PMID   7526294. S2CID   37856308.
5. Wan CY, Wilkins TA (1993). "Spermidine facilitates PCR amplification of target DNA". PCR Methods and Applications. 3 (3): 208–10. doi: 10.1101/gr.3.3.208 . PMID   8118404.
6. Cull M, McHenry CS (1990). "Preparation of extracts from prokaryotes". Guide to Protein Purification. Methods in Enzymology. Vol. 182. pp. 147–53. doi:10.1016/0076-6879(90)82014-S. ISBN   978-0-12-182083-1. PMID   2107372.
7. Blethen SL, Boeker EA, Snell EE (1968). "Arginine decarboxylase from Escherichia coli. I. Purification and specificity for substrates and coenzyme". The Journal of Biological Chemistry. 243 (8): 1671–7. doi: 10.1016/S0021-9258(18)93498-8 . PMID   4870599.
8. Wu WH, Morris DR (1973). "Biosynthetic arginine decarboxylase from Escherichia coli. Subunit interactions and the role of magnesium ion". The Journal of Biological Chemistry. 248 (5): 1696–9. doi: 10.1016/S0021-9258(19)44246-4 . PMID   4571774.
9. Tabor CW, Tabor H (1984). "Polyamines". Annual Review of Biochemistry. 53: 749–90. doi:10.1146/annurev.bi.53.070184.003533. PMID   6206782.
10. Krug MS, Berger SL (1987). "First-strand cDNA synthesis primed with oligo(dT)". Guide to Molecular Cloning Techniques. Methods in Enzymology. Vol. 152. pp. 316–25. doi:10.1016/0076-6879(87)52036-5. ISBN   978-0-12-182053-4. PMID   2443800.
11. Karkas JD, Margulies L, Chargaff E (1975). "A DNA polymerase from embryos of Drosophila melanogaster. Purification and properties". The Journal of Biological Chemistry. 250 (22): 8657–63. doi: 10.1016/S0021-9258(19)40721-7 . PMID   241752.
12. Bouché JP (1981). "The effect of spermidine on endonuclease inhibition by agarose contaminants". Analytical Biochemistry. 115 (1): 42–5. doi:10.1016/0003-2697(81)90519-4. PMID   6272602.
13. Ali MA, Poortvliet E, Strömberg R, Yngve A (2011). "Polyamines in foods: development of a food database". Food Nutr Res. 55: 5572. doi:10.3402/fnr.v55i0.5572. PMC   3022763 . PMID   21249159.
14. Ciba-Geigy, ed. (1977), "Sperma", Wissenschaftliche Tabellen Geigy (in German), vol. Teilband Körperflüssigkeiten (8 ed.), Basel: CIBA-GEIGY Limited, pp. 181-189
15. "Brochure on Polyamines, rev. 2" (PDF). Japan: Oryza Oil & Fat Chemocial Co., Ltd. 2011-12-26. Archived from the original (PDF) on 2016-03-03. Retrieved 2013-11-06.
16. T.M. Klein, T. Gradziel, M.E. Fromm, J.C. Sanford (1988). "Factors influencing gene delivery into Zea mays cells by high–velocity microprojectiles". Nature Biotechnology. 6 (5): 559–63. doi:10.1038/nbt0588-559. S2CID   32178592.
17. Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A (2016). "Cardioprotection and lifespan extension by the natural polyamine spermidine". Nature Medicine. 22 (12): 1428–1438. doi:10.1038/nm.4222. PMC   5806691 . PMID   27841876.
18. Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, et al. (November 2009). "Induction of autophagy by spermidine promotes longevity". Nat. Cell Biol. 11 (11): 1305–14. doi:10.1038/ncb1975. PMID   19801973. S2CID   3126330. Archived from the original on May 30, 2020.
19. "The Ultimate Spermidine Guide: Benefits, Side Effects & How To Take". Prohormones. Retrieved 2022-07-29.
20. Lefèvre PL, Palin M, Murphy BD (2011). "Polyamines on the Reproductive Landscape" . Endocrine Reviews. 32 (5): 694–712. doi:10.1210/er.2011-0012. PMID   21791568 . Retrieved 2022-07-29.
21. Li B, Hu X, Yang Y, Zhu M, Zhang J, Wang Y, Pei X, Zhou H, Wu J (2019-09-06). "GAS5/miR-21 Axis as a Potential Target to Rescue ZCL-082-Induced Autophagy of Female Germline Stem Cells In Vitro". Molecular Therapy. Nucleic Acids. 17: 436–447. doi:10.1016/j.omtn.2019.06.012. ISSN   2162-2531. PMC   6637212 . PMID   31319247.
22. Frugier M, Florentz C, Hosseini MW, Lehn JM, Giegé R (July 1994). "Synthetic polyamines stimulate in vitro transcription by T7 RNA polymerase". Nucleic Acids Res. 22 (14): 2784–90. doi:10.1093/nar/22.14.2784. PMC   308248 . PMID   8052534.
23. Mertelsmann R (June 1969). "Purification and some properties of a soluble DNA-dependent RNA polymerase from nuclei of human placenta". Eur. J. Biochem. 9 (3): 311–8. doi: 10.1111/j.1432-1033.1969.tb00610.x . PMID   5795512.

External links

• Safety Data Sheet