The Introduction of Sulfation
Sulfation refers to the biochemical process by which an inorganic sulfate forms a biologically active organic sulfate under the catalysis of an enzyme. Elemental sulfur in the form of inorganic sulfates can only be bioavailable after metabolic activation, such as 5'-adenosine-5' phosphosulfate (APS) and 3'-phosphate glands 3'-phosphoadenosine-5'-phosphosulfate (PAPS). The synthesis of PAPS is two-step catalysis of ATP (adenosine triphosphate) sulfatase and APS kinase. The inorganic sulfate reacts with ATP to form APS and pyrophosphate; then, APS reacts with ATP to form PAPS and ADP (adenosine diphosphate). The family of sulfuric acid transferases is responsible for the transfer of activated sulfate groups from PAPS to various biomolecules such as hormones, neurotransmitters, carbohydrates and protein tyrosine. In addition, APS and PAPS are also used to synthesize reducing sulfur metabolites, such as the components of many proteins - methionine and cysteine.
The Role of Sulfation
Sulfation is important in the body for protein sulfation and polysaccharide sulfation; for certain neuropeptides, tyrosine sulfation is necessary for its activity. For example, the hormonal activity of CCK depends on the sulfation of tyrosine residues, since the activity of sulfated CCK is 260 times of non-sulfated CCK. Tyrosine sulfate may be a form of a single translation product that forms a variety of phenotypes. For example, the ability of gastrin to stimulate the secretion of gastric acid is not affected by the sulfur acidification. However, after the sulfur acidification of tyrosine acid, gastrin has the second biological activity. Andersen and Stodil observed that the gastrin precursor was processed differently in various tissues. The extent to which macromolecules are processed into small molecules is related to the presence of tyrosine sulfation. Tyrosine sulfation occurs in the cis-Golgi network. Therefore, it is almost certain that the sulfation occurs before the enzymatic hydrolysis of the peptide precursor, so sulfation promotes the processing of the gastrin precursor. Recently, Frioderieh et al. have done a series of studies on the yolk pheromone l of Drosophila, which showed that tyrosine sulfation can affect the transport of secreted proteins. A variety of polysaccharides can enhance biological activity, and this activity is more pronounced after the polysaccharides is sulfated. The dextran sulfate is a polyclonal activator of B lymphocytes and induces proliferation of peripheral blood T lymphocytes. Zhen huanguo studied the sulfating astragalus polysaccharide sulfate (sAPS), sulfate epimedium polysaccharide (sEPS) and sulfated angelica polysaccharides (sCAPS) influence on chicken peripheral blood lymphocyte proliferation; the results showed that appropriate doses of the five kinds of sulfated polysaccharide can alone or together with sword bean grain globulin (ConA) stimulate lymphocyte proliferation and present a certain effect. The antiviral activity of sulfated polysaccharides is mainly due to the characteristics of its polyanions, while the polyanionic properties are mainly derived from the sulfate groups in its molecules. The strongly negatively charged sulfate polyanions bind to viruses or cell surface and positively charged molecules, which can be stereoscopically inhibition of virus adsorption; sulfated polysaccharides can also directly inhibit certain steps of virus entry into cells or inhibition of their entry into cells; in addition, sulfated polysaccharides can also inhibit the expression of viral antigens, inhibit the formation of syncytia and inhibit reverse transcriptase activity and antioxidant effects. Polysaccharides generally have anticoagulant activity after being sulfated and can be an effective substitute for heparin. Xu Zhongping found that laminaria sulfate can inhibit the adhesion of basic fibroblast growth factor (bFGF) and bFGF-dependent cells, thereby effectively inhibiting the formation of tubular structures of endothelial cells and inhibiting the formation of chicken chorioallantoic membrane and has anti-mouse RIF-1 tumor growth activity.
The Regulation of Sulfation
Biomacromolecules are the main bearers of various life activities such as polysaccharides, proteins and nucleic acids, which have the functions of enhancing immunity, anti-aging, anti-oxidation, anti-cancer and anti-rheumatoid. Sulfated polysaccharides and proteins have received extensive attention in recent years due to their biological activities such as anti-oxidation, anti-viral, and anti-tumor. The introduction of sulphate changes the physical and chemical properties of biomacromolecules, thereby affecting their biological activity. When no sulfate group is introduced, some polysaccharides have no biological activity such as oxidation resistance and anticoagulation. After the introduction of sulfate, polysaccharides and proteins are given biological activities such as anti-oxidation and anti-clotting. Carrageenan and heparin have the activity of inhibiting herpes virus replication and anticoagulation, but if the sulfate of these polysaccharides is removed, the above activity disappears, indicating that the introduction of sulfate groups has an improvement on the biological activity of polysaccharides and proteins. The sulfation properties of biomacromolecules are not only related to the content of sulfate, but also related to molecular weight and structure. Yamada et al. prepared sulfated carrageenan and found that low molecular sulfated carrageenan (molecular weight 50000 Da) has higher anti-HIV activity than other molecular weight sulfated carrageenan. The low molecular sulfated chitosan synthesized by Xing et al has stronger scavenging ability to superoxide anion radical and hydroxyl radical than polymer sulfated chitosan. It is indicated that the bioactivity of the sulfated product is closely related to the molecular weight after the sulfation modification.