Spermidine is a type of polyamine. Polyamines are small, fatty, polycationic (-NH3+) biomolecules. There are four main polyamines in mammals: spermine, spermidine, putrescine and cadaverine. Spermine belongs to the tetramines, spermidine belongs to the triamines, putrescine and cadaverine belong to the diamines. Different numbers of amino groups give them different physiological properties.
Spermidine in humans
Spermidine not only exists in semen, but is also widely distributed in other tissues and cells of the human body. The intracellular spermidine concentration mainly depends on four factors:
①Intracellular synthesis:
Arginine → putrescine → spermidine ← spermine. Arginine is the main raw material for the synthesis of spermidine in cells. It is catalyzed by arginase to generate ornithine and urea. Ornithine is then used to generate putrescine under the action of ornithine decarboxylase (ODC1). This is the rate-limiting step), putrescine generates spermidine under the action of spermidine synthase (SPDS). Spermidine can also be produced by the degradation of spermine.
②Extracellular uptake:
Divided into food intake and intestinal microbial synthesis. Foods rich in spermidine include wheat germ, natto, soybeans, mushrooms, etc. Spermine and spermidine ingested from food are rapidly absorbed from the intestines and distributed without degradation, so the concentration of spermidine in the blood is Concentrations are highly diverse. Probiotic bacteria in the intestinal microbiota such as Bifidobacterium can also synthesize spermidine.
③Catabolism:
Spermine in the body is gradually decomposed into spermidine and putrescine by N1-acetyltransferase (SSAT), polyamine oxidase (PAO) and other amine oxidases, while putrescine is further converted into aminobutyric acid by oxidases. Finally, amine ions and carbon dioxide are generated and excreted from the body.
④Age:
The concentration of spermidine changes with age. Researchers measured the concentration of polyamines in various tissues and organs of 3-week-old, 10-week-old and 26-week-old mice and found that it was basically maintained in the pancreas, brain and uterus. Changes in the intestine decrease slightly with age, and decrease significantly in the thymus, spleen, ovary, liver, stomach, lung, kidney, heart and muscle. It is not difficult for us to speculate that the reasons for this change include dietary changes, changes in intestinal flora structure, reduced activity of polyamine synthase, etc.
Natural target of spermidine
Why is such a simple small molecule an essential key substance for the human body? The secret actually lies in its structure: Spermidine is a polycationic (-NH3+) fatty amine small molecule that exists in a multi-protonated form under physiological pH conditions, with positive ions distributed throughout the carbon chain. Electric charge, has strong physiological activity.
Therefore, whether it is nucleic acids, phospholipids, acidic proteins containing acidic residues, pectic polysaccharides containing carboxyl groups and sulfates, or neurotransmitters and hormones (dopamine, epinephrine, serotonin, thyroid hormone, etc.) with similar structures, Potentially a target for spermidine binding. The more critical ones are:
① Nucleic acid:
Studies have found that most polyamines exist in the form of polyamine-RNA complexes within cells, with 1-4 equivalents of polyamine bound per 100 equivalents of phosphate compounds. Therefore, the main role of spermidine is related to the structural changes and translation of RNA, such as affecting various stages of protein synthesis by affecting the secondary structure of mRNA, tRNA and rRNA. Spermidine can also form stable "bridges" between double-helical DNA strands, reducing the accessibility of free radicals or other DNA-damaging agents, and protecting DNA from thermal denaturation and X-ray radiation.
②Protein:
Spermidine can bind to proteins carrying large negative charges and change the spatial conformation of the protein, thereby affecting its physiological function. Examples include protein kinases/phosphatases (an important link in multiple signal transduction pathways), enzymes involved in histone methylation and acetylation (affecting gene expression by changing epigenetics), acetylcholinesterase (an important component of neurodegenerative diseases). one of the therapeutic drugs), ion channel receptors (such as AMPA, AMDA receptors), etc.
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Post time: Oct-23-2024
