Spermidine

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Spermidine
N1-(3-aminopropyl)butane-1,4-diamine 200 2.svg
Spermidine-3D-balls.png
Names
Preferred IUPAC name
N1-(3-Aminopropyl)butane-1,4-diamine
Identifiers
3D model (JSmol)
3DMet
1698591
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.004.264 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 204-689-0
454510
KEGG
MeSH Spermidine
PubChem CID
RTECS number
  • EJ7000000
UNII
UN number 2735
  • InChI=1S/C7H19N3/c8-4-1-2-6-10-7-3-5-9/h10H,1-9H2 X mark.svgN
    Key: ATHGHQPFGPMSJY-UHFFFAOYSA-N X mark.svgN
  • NCCCCNCCCN
Properties
C7H19N3
Molar mass 145.250 g·mol−1
AppearanceColourless liquid
Odor Ichtyal, ammoniacal
Density 925 mg mL−1
Melting point 22 to 25 °C (72 to 77 °F; 295 to 298 K)
145 g L−1 (at 20 °C)
log P −0.504
UV-vismax)260 nm
Absorbance 0.1
1.479
Hazards
GHS labelling:
GHS-pictogram-acid.svg
Danger
H314
P280, P305+P351+P338, P310
Flash point 112 °C (234 °F; 385 K)
Related compounds
Related amines
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Spermidine is a polyamine compound (C
7
H
19
N
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. Polyamine synthesis.svg
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:

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]

FoodSpermidine
mg/kg
notes & refs
Wheat germ243 [15]
Soybean, dried207Japanese [13]
Cheddar, 1yr old199 [13]
Soybean, dried128German [13]
Mushroom89Japanese [13]
Rice bran50 [13]
Chicken liver48 [13]
Green peas46 [13]
Mango30 [13]
Chickpea29 [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

See also

Related Research Articles

<span class="mw-page-title-main">Putrescine</span> Foul-smelling organic chemical compound

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 putrefying flesh, but also contributes to other unpleasant odors.

<span class="mw-page-title-main">Ornithine decarboxylase</span>

The enzyme ornithine decarboxylase catalyzes the decarboxylation of ornithine to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids and forms a homodimer.

<span class="mw-page-title-main">DNA polymerase</span> Form of DNA replication

A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create two identical DNA duplexes from a single original DNA duplex. During this process, DNA polymerase "reads" the existing DNA strands to create two new strands that match the existing ones. These enzymes catalyze the chemical reaction

Agmatine, also known as 4-aminobutyl-guanidine, was discovered in 1910 by Albrecht Kossel. It is a chemical substance which is naturally created from the amino acid arginine. Agmatine has been shown to exert modulatory action at multiple molecular targets, notably: neurotransmitter systems, ion channels, nitric oxide (NO) synthesis, and polyamine metabolism and this provides bases for further research into potential applications.

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 polycation at physiological pH. Spermine is associated with nucleic acids and is thought to stabilize helical structure, particularly in viruses. It functions as an intracellular free radical scavenger to protect DNA from free radical attack. Spermine is the chemical primarily responsible for the characteristic odor of semen.

<span class="mw-page-title-main">Thromboxane-A synthase</span> Mammalian protein found in Homo sapiens

Thromboxane A synthase 1 , also known as TBXAS1, is a cytochrome P450 enzyme that, in humans, is encoded by the TBXAS1 gene.

<span class="mw-page-title-main">Myricetin</span> Chemical compound

Myricetin is a member of the flavonoid class of polyphenolic compounds, with antioxidant properties. Common dietary sources include vegetables, fruits, nuts, berries, tea, and red wine.

<span class="mw-page-title-main">T7 RNA polymerase</span> Class of enzymes

T7 RNA Polymerase is an RNA polymerase from the T7 bacteriophage that catalyzes the formation of RNA from DNA in the 5'→ 3' direction.

<span class="mw-page-title-main">Polynucleotide phosphorylase</span> Class of enzymes

Polynucleotide Phosphorylase (PNPase) is a bifunctional enzyme with a phosphorolytic 3' to 5' exoribonuclease activity and a 3'-terminal oligonucleotide polymerase activity. That is, it dismantles the RNA chain starting at the 3' end and working toward the 5' end. It also synthesizes long, highly heteropolymeric tails in vivo. It accounts for all of the observed residual polyadenylation in strains of Escherichia coli missing the normal polyadenylation enzyme. Discovered by Marianne Grunberg-Manago working in Severo Ochoa's lab in 1955, the RNA-polymerization activity of PNPase was initially believed to be responsible for DNA-dependent synthesis of messenger RNA, a notion that was disproven by the late 1950s.

Spermine synthase is an enzyme that converts spermidine into spermine. This enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">Endothelial NOS</span> Protein and coding gene in humans

Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. This enzyme is one of three isoforms that synthesize nitric oxide (NO), a small gaseous and lipophilic molecule that participates in several biological processes. The other isoforms include neuronal nitric oxide synthase (nNOS), which is constitutively expressed in specific neurons of the brain and inducible nitric oxide synthase (iNOS), whose expression is typically induced in inflammatory diseases. eNOS is primarily responsible for the generation of NO in the vascular endothelium, a monolayer of flat cells lining the interior surface of blood vessels, at the interface between circulating blood in the lumen and the remainder of the vessel wall. NO produced by eNOS in the vascular endothelium plays crucial roles in regulating vascular tone, cellular proliferation, leukocyte adhesion, and platelet aggregation. Therefore, a functional eNOS is essential for a healthy cardiovascular system.

<span class="mw-page-title-main">Calcium/calmodulin-dependent protein kinase type II subunit alpha</span> Protein-coding gene in the species Homo sapiens

Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMKIIα), a.k.a.Ca2+/calmodulin-dependent protein kinase II alpha, is one subunit of CamKII, a protein kinase (i.e., an enzyme which phosphorylates proteins) that in humans is encoded by the CAMK2A gene.

<span class="mw-page-title-main">Cyclooxygenase-1</span> Enzyme

Cyclooxygenase 1 (COX-1), also known as prostaglandin-endoperoxide synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene. In humans it is one of two cyclooxygenases.

<span class="mw-page-title-main">DYNLL1</span> Protein-coding gene in humans

Dynein light chain 1, cytoplasmic is a protein that in humans is encoded by the DYNLL1 gene.

<span class="mw-page-title-main">SAT1 (gene)</span> Protein-coding gene in the species Homo sapiens

Diamine acetyltransferase 1 is an enzyme that in humans is encoded by the SAT1 gene found on the X chromosome.

<span class="mw-page-title-main">SMOX</span> Enzyme

Spermine oxidase is an enzyme that in humans is encoded by the SMOX gene.

Jerard Hurwitz was an American biochemist who co-discovered RNA polymerase in 1960 along with Sam Weiss, Audrey Stevens, and James Bonner. He most recently worked at the Sloan-Kettering Institute in New York studying DNA replication in eukaryotes and its control.

A polyamine is an organic compound having more than two 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. Most aromatic polyamines are crystalline solids at room temperature.

<span class="mw-page-title-main">DNA polymerase alpha catalytic subunit</span> Protein-coding gene in humans

DNA polymerase alpha catalytic subunit is an enzyme that in humans is encoded by the POLA1 gene.

BpsA is a single-module non-ribosomal peptide synthase (NRPS) located in the cytoplasm responsible for the process of creating branched-chain polyamines, and producing spermidine and spermine. It has a singular ligand in its structure involved with Fe3+ and PLIP interactions. As seen by its EC number, it is a transferase (2) that transfers an alkyl or aryl group other than methyl groups (5) (2.5.1). BpsA was first discovered in the archaea Methanococcus jannaschii and thermophile Thermococcus kodakarensis and since then has been used in a variety of applications such as being used as a reporter, researching phosphopantetheinyl transferase (PPTase), and for NRPS domain recombination experiments it can be used as a model. Both (hyper)thermophilic bacteria and euryarchaeotal archaea seem to conserve BpsA and orthologs as branches chains polyamines are crucial for survival. There is also a second type of BpsA also known as Blue-pigment indigoidine synthetase that produces the pigment indigoidine and is found in organisms like Erwinia chrysanthemi. However, not much seems to be known about this variant except that it is a synthase, and it does not yet appear to be classified under an EC number.

References

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