Background and overview[1-2]
Sphingolipid phosphate composed of sphingosine, fatty acids, phosphate groups and choline. Such as ceramide. Together with proteins and polysaccharides, it forms a protective layer for nerve fibers or axons and has an insulating effect. Sphingomyelin is a natural component in food. In recent years, sphingomyelin in food has gradually attracted people’s attention. The main reason is that it is closely related to diseases caused by cholesterol, fatty acids, and mycotoxins in the human body. Therefore, The relationship between sphingomyelin in food and human health has become a feature of current research. At present, the metabolic pathway of sphingomyelin in the human body is not very clear, but studies have shown that its two major metabolites, ceramide and sphingosine, are involved in physiological activities such as cell growth, differentiation, and apoptosis in the body.
Source[2]
Sphingomyelin is contained in most foods, but the content of sphingomyelin in different foods varies greatly. The content of sphingomyelin in fruits and some vegetables is less than 100 μmol/kg, while in eggs, dairy products and soy foods Up to 2000μmol/kg or more. Sphingomyelin in food can be measured using two methods. One is direct measurement, such as high performance liquid chromatography (HPLC) and gas chromatography (GC) to determine the content of sphingomyelin in food; the other is indirect measurement, such as The content of sphingomyelin in food can be estimated by measuring the phosphorus content of sphingomyelin, the hexose content or lipid and nitrogen content in ceramide.
Sphingomyelin metabolism[2]
Sphingomyelin is not easily absorbed in the stomachs of rats and mice, but it is quickly absorbed by enterocytes in the small intestine and colon and decomposes into fatty acids (fatty aldehydes) or re-synthesizes new sphingolipid substances. The reason is that it The intestinal lumen contains sphingomyelinase, glucosylceramidase and ceramidase activity factors. When rats were fed radioactively labeled sphingomyelin, a small amount of labeled sphingomyelin was also found in their blood and liver. Sphingomyelin, and taurocholic acid-dependent neutral sphingomyelinase was found in human pancreatic juice, and an alkaline sphingomyelinase was also found in bile, suggesting that dietary sphingomyelin is partially transported into the circulation system and digestive system.
But not all ingested sphingomyelin will be decomposed and absorbed. Rats are given a certain dose of sphingomyelin, 25% of which is excreted through feces, and 10% of this 25% is sphingomyelin prototype molecules, 80% to 90% % is ceramide, 3% to 6% is free sphingosine, and the ratio is directly related to the amount of sphingomyelin consumed; it has been recently reported that newborn infants given formula milk added with sphingomyelin are significantly different from those given normal formula milk. In comparison, the number of E. coli in the feces of the former was significantly reduced; it was also found that sphingomyelin in the germ-free rats was decomposed and absorbed very little. In short, it is suggested that the intestine and intestinal flora play a very important role in the absorption and metabolism of sphingomyelin.
Biological functions[2]
Sphingomyelin is mainly located on cell membranes, lipoproteins (especially LDL) and other lipid-rich tissue structures. Sphingomyelin is very important for maintaining the structure of cell membranes, especially the micro-control functions of cell membranes (such as membrane invagination). It can Regulates the activities of growth factor receptors and supercellular matrix proteins, and provides binding sites for some microorganisms, microbial toxins, and viruses. Many extracellular drugs and external stimuli such as tumor necrosis factor (TNFσ), interleukin (IL-1), gamma radiation, interferon (IFNγ), etc. can activate sphingomyelinase to hydrolyze sphingomyelin and release ceramide. As the second messenger, it can regulate the activity of the following substances: protein kinase C isoenzyme (PKCζ), protein phosphatase (CAPP) and protein kinase (CAPK).
As intracellular factors, they activate NF-κB, regulate the expression of c-myc, induce cyclooxygenase (CoX) and inhibit phospholipid D [6]. The final effect of ceramide shows different biochemical activities on different types of cells and is regulated by other channels, such as PKC channels. Cells show cell differentiation, cell cycle arrest, and apoptosis. For cells stimulated by platelet-derived growth factor (PDGF) and serum factors, sphingosine 1-phosphate mediates the signal transduction pathway of cell proliferation. These two lipid molecules are metabolites of sphingomyelin, but their effects are antagonistic. , the life and death of cells often depend on which one plays a dominant role.
Sphingomyelin and disease[2-3]
1. Sphingomyelin and colon cancer
Colon cancer is a type of cancer that is closely related to diet, and its incidence ranks third among all cancers in the world. Current research has found that sphingomyelin, in addition to constituting the structure of cell biofilms and having biofilm functions, also has a significant cancer-inhibiting effect. Its cancer-suppressing mechanism is one of the current research hotspots. The following in vivo and in vitro experimental research results show that the anti-cancer effect of sphingomyelin is mainly manifested in two aspects.
1) In vivo experiment: After treating healthy female CF1 mice with 1,2-dimethylhydrazine hydrochloride (DMH), the mice were fed with feed containing 0.025% to 0.1% sphingomyelin for 28 weeks, and then changed to basal feed. Feed for 24 weeks. The results showed that sphingomyelin did not affect the weight gain of mice; the incidence of colon tumors in the sphingomyelin group was 20%, while that of the control mice was 47% (P found. Although the occurrence of colon cancer has been confirmed to be related to diet, The factors that play a major role are still controversial.
Some foods rich in sphingomyelin (���dairy and soy) have attracted the attention of cancer researchers. For example, dairy reduces the number of abnormal crypts in rats, reduces the proliferation of abnormal colonic epithelial cells, and is associated with reduced colon cancer development in humans. Based on the above research results, sphingomyelin in the diet may have an impact on the occurrence of human colon cancer. Research on the anti-cancer mechanism of sphingomyelin may be helpful in explaining the anti-cancer functions of dairy products and other foods.
2) In vitro experiments: Ceramide, as the second messenger molecule that mediates various biological effects, has been deeply studied, but its role in apoptosis has only begun to be recognized in recent years. Studies have shown that TNFα, fatty acid synthase (Fas), ionizing rays and other stimulating factors produce ceramide through the sphingomyelin recycling pathway to act as the second signal phosphorous acid to mediate cell apoptosis. At present, it is discovered that more and more stimulating factors, including cytokines, immune molecules, ultraviolet rays, heat shock, hormones and anti-cancer drugs, can induce cell apoptosis through this pathway. Studies have reported that ceramide can induce apoptosis in a variety of tumor cells, such as breast cancer cells (MCF-7), colorectal cancer cells (LoVo), prostate cancer cells (LNCaP), etc.
2. Sphingomyelin and arteriosclerosis
1) The effect of sphingomyelin on cholesterol metabolism The effect of sphingomyelin on cholesterol metabolism is as follows: (1) It has a certain influence on the conversion of cholesterol into bile acids, cholesterol esters, and other metabolites; (2) It can regulate β- Activity of hydroxyβ-methylglutarate-CoA reductase; (3) Sphingomyelin promotes the conversion of intracellular cholesterol esters into free cholesterol. (4) Sphingomyelin can promote high-density lipoprotein-3 to mediate intracellular cholesterol efflux.
2) The effects of cholesterol and other lipids on sphingomyelin metabolism. The effects of cholesterol and other lipids on sphingomyelin metabolism are as follows: (1) 25-hydroxycholesterol, a cholesterol synthesis inhibitor, can stimulate the metabolism of Chinese hamster ovary cells. The synthesis of sphingomyelin; (2) The cholesterol content provided in the diet has a certain impact on the synthesis and metabolism of sphingomyelin in the body; (3) The lack of essential fatty acids will reduce the formation of ceramide in the skin.
The connection between sphingomyelin and cholesterol has puzzled researchers for decades. One existing molecular-level explanation for the cellular connection between these two lipids is their collective control of microcontroller functions, such as within membranes. trap. Both short-term and long-term animal experiments have shown that rats fed sphingomyelin-containing feeds have a 30% reduction in plasma cholesterol content compared with the control group. In vitro studies have found that the amount of sphingomyelin in the intestinal lumen epithelium is related to the cholesterol content. Absorption is closely related. The above correlation between sphingomyelin and cholesterol illustrates the role of sphingomyelin in atherosclerosis.
3. The role of SM and its metabolites in lung diseases
Respiratory diseases have always been an important disease that threatens human health, and the incidence rate remains high. Studies have found that sphingolipid metabolites are related to the pathogenesis of various lung diseases.
1) S1P and bronchial asthma: Bronchial asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction. Allergen stimulation is the most important factor in inducing asthma, and mast cells are the effector cells that play a central role in allergic diseases. Allergens bind to the high-affinity lgE receptor FcR1 (Fcreceptor1) on the surface of mast cells, leading to a variety of biological effect pathways. of activation. S1P/SPHK is one of the signaling pathways that induces FcR1 activation. As early as 1996, Choi et al. [7] first discovered that FcR1 stimulation induced an increase in SPHK activity in mouse mast cells, which promoted an increase in S1P levels in the body.
In addition, FcR1 also inhibits the production of SPHK inhibitor DHS (D, L-threodihydrosphingosine) by stimulating Ca2+ mobilization, thereby increasing S1P synthesis. Studies have proposed that the gradient difference between sphingosine and S1P in mouse mast cells has opposite effects on regulating mast cell activity. S1P leads to FcR1 activation by activating the MAPK pathway, causing mast cell degranulation and the release of leukotrienes, while sphingosine It has the effect of inhibiting the above pathways.
2) S1P and pneumonia: Pneumonia is the most common infectious inflammatory disease of the lungs. S1PR3 is significantly expressed on the membrane of peripheral blood neutrophils in patients with pneumonia, thereby activating S1PR3 to enhance cell adhesion and migration. In the lipopolysaccharide-induced macrophage inflammation model, S1P can switch macrophages from pro-inflammatory to anti-inflammatory effects and cause a decrease in pro-inflammatory factors such as TNF-α and IL-12. Recent studies have shown that various pro-inflammatory factors can cause up-regulation of intracellular SPHK1. Activating the SPHK1/S1P pathway can activate its downstream signals and induce the production of pro-inflammatory factors. Therefore, it is known that SPHK1/S1P plays a key role in the inflammatory response.
4. SM and its metabolites and HIV
TNFa is known to be an activator of HIV proto-oncovirus integrated into the chromosomes of T lymphocytes and monocyte macrophages. If HIV carriers are given competitive lipid analogs of Cer, HIV can be prevented. replication, which will have a great blocking effect on the spread of HIV.
Main reference materials
[1] Nutritional Science Dictionary
[2] Research progress on sphingomyelin
[3] Research progress on sphingomyelin and its metabolites and various diseases
