Spermidin: the pathway in the body

Spermidin is part of the pathway “Spermidine”. This page shows the whole pathway; the station of Spermidin is highlighted.

Where this laboratory value sits: Spermidine — three nitrogen sites. Spermidine synthase attaches an aminopropyl group from dcSAM to putrescine. Spermidine also comes from food, such as wheat germ, soybeans and aged cheese, and from gut bacteria. Source 1, 5

In brief

Spermidine belongs to the polyamines, small molecules carrying several positive charges. Cells build it from ornithine; it attaches to RNA and DNA and provides the piece from which the amino acid hypusine is formed on the factor eIF5A.

The pathway step by step

1. Ornithine → Putrescine ODC · vitamin B6 (PLP) Ornithine decarboxylase removes the carboxyl group from ornithine. The enzyme is made and broken down very quickly; this is how the cell regulates the amount of polyamines. Source 1
2. Putrescine → Spermidine Spermidine synthase · dcSAM Spermidine synthase attaches an aminopropyl group from dcSAM to putrescine. Spermidine also comes from food, such as wheat germ, soybeans and aged cheese, and from gut bacteria. Source 1, 5
3. Spermidine → Spermine Spermine synthase · dcSAM A second aminopropyl group turns spermidine into spermine. Both polyamines carry several positive charges and therefore bind to negatively charged molecules. Source 1
4. Spermine → Polyamine recycling SSAT, PAO · acetyl-CoA The enzyme SSAT attaches an acetyl group, and polyamine oxidase turns the product back into spermidine or putrescine. Acetylated forms leave the body in the urine. Source 1
5. SAM → dcSAM AdoMetDC The decarboxylase AdoMetDC removes the carboxyl group from SAM. The resulting dcSAM supplies the aminopropyl groups for spermidine and spermine. Source 1
6. Spermidine in the cell → eIF5A with hypusine DHS, DOHH · oxygen Two enzymes transfer part of the spermidine to the factor eIF5A. This creates hypusine, an amino acid found only in this one protein. Source 3
7. eIF5A with hypusine → Protein synthesis · ribosome With hypusine, eIF5A helps the ribosome past difficult stretches, such as runs of several prolines. Without this modification, protein synthesis stalls at exactly such stretches. Source 3
8. Spermidine in the cell → Binding to RNA and DNA Polyamines attach to nucleic acids and stabilise their folding. In this way they influence how RNA is read and how DNA is packaged. Source 1, 2
9. Spermidine in the cell → Autophagy EP300 inhibited In cell and animal models, spermidine inhibits the acetyltransferase EP300. Autophagy proteins then remain unacetylated, and the cell begins to break down and recycle its own components. Source 4, 2

Cofactors in this pathway

• Ornithine — Starting material from which ornithine decarboxylase makes putrescine Source 1In the ORY catalogue as a laboratory value: Ornithin
• Arginine — Amino acid from which ornithine arises in the urea cycle Source 1In the ORY catalogue as a laboratory value: Arginin
• Vitamin B6 — Cofactor (PLP) of ornithine decarboxylase Source 1In the ORY catalogue as a laboratory value: Vitamin B6
• SAM (from methionine) — Converted into dcSAM and thereby provides the aminopropyl group for spermidine and spermine Source 1In the ORY catalogue as a laboratory value: Methionin
• NAD⁺ — Cofactor of deoxyhypusine synthase, which transfers the spermidine part onto eIF5A Source 7, 3In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Iron — Two iron atoms in the active site of deoxyhypusine hydroxylase Source 8, 3In the ORY catalogue as a laboratory value: Eisen
• Acetyl-CoA — Donor of the acetyl group for SSAT during the breakdown of the polyamines Source 1

What acts on this pathway

• Eflornithine — Eflornithine binds tightly to ornithine decarboxylase and switches it off permanently. This has been described for local application to the skin. Source 6

Sources

1. Pegg AE. Mammalian polyamine metabolism and function. IUBMB Life 2009 · PubMed 19603518
2. Madeo F, Eisenberg T, Pietrocola F et al. Spermidine in health and disease. Science 2018 · PubMed 29371440
3. Park MH, Wolff EC. Hypusine, a polyamine-derived amino acid critical for eukaryotic translation. J Biol Chem 2018 · PubMed 30257869
4. Hofer SJ, Simon AK, Bergmann M et al. Mechanisms of spermidine-induced autophagy and geroprotection. Nat Aging 2022 · PubMed 37118547
5. Zou D, Zhao Z, Li L et al. A comprehensive review of spermidine: Safety, health effects, absorption and metabolism, food materials evaluation, physical and chemical processing, and bioprocessing. Compr Rev Food Sci Food Saf 2022 · PubMed 35478379
6. Balfour JA, McClellan K. Topical eflornithine. Am J Clin Dermatol 2001 · PubMed 11705097
7. Chen M, Gai Z, Okada C et al. Flexible NAD(+) Binding in Deoxyhypusine Synthase Reflects the Dynamic Hypusine Modification of Translation Factor IF5A. Int J Mol Sci 2020 · PubMed 32752130
8. Frey AG, Nandal A, Park JH et al. Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase. Proc Natl Acad Sci U S A 2014 · PubMed 24843120

Whole pathway: Spermidine

Related pathways

• Methylation: methionine and homocysteine — sam
• Arginine and nitric oxide — ornithine
• Vitamin B12 — sam
• Carnitine — Vitamin B6, Methionin
• Dopamine, noradrenaline, adrenaline — Vitamin B6, Methionin

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert approval pending
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