After synthesis within the plasma membrane, HA gets secreted from the cell into the extracellular space unmodified. These monosaccharide building blocks are synthesized in the cell cytoplasm and are recruited to the plasma membrane by diffusion for HA synthesis. Instead, the structure consists of sequentially bound glucuronic acid and N-acetylglucosamine residues. Hyaluronic acid (HA) has the simplest structure of all GAGs and does not require additional sulfation of functional groups in the Golgi apparatus as do the other GAGs. The molecular structure of each of the major categories appears below. Variations in the type of monosaccharides and the presence or absence of modification by sulfation results in the different major categories of GAGs, including hyaluronic acid, heparin/heparan sulfate, chondroitin sulfate/dermatan sulfate, and keratan sulfate. ![]() The molecular structures of individual GAGs are in the following section.Īs the name suggests, the “glyco-” prefix refers to galactose or a uronic sugar (glucuronic acid or iduronic acid) attached to an aminoglycan, or amino sugar ( N-acetylglucosamine or N-acetylgalactosamine). Modification by epimerization of the resulting polysaccharide structures by enzymatic action is responsible for the production of the various molecular structures of GAGs and their resulting properties. Keratan sulfate is the only sulfated GAG that is not linked to a PG protein core by this mechanism and is instead linked by various other compounds depending on the subtype of keratan sulfate, described in further detail below. The tethering process for the GAGs heparin/heparan sulfate, chondroitin sulfate, and dermatan sulfate occurs through a serine amino acid residue present on the protein core that connects to a common tetrasaccharide linker between the GAG and PG. The sulfated GAGs synthesized in the Golgi apparatus undergo covalent linkage to anchor proteins known as proteoglycans (PGs). The availability of PAPS for sulfation of GAGs significantly affects the biosynthetic rate of production of sulfated GAGs. Īll other GAGs require additional modification steps that take place in and around the Golgi apparatus, including sulfation of functional groups by the action of the sulfate donor compound 3`-phosphoadenosine-5`-phosphosulfate (PAPS). Instead of undergoing modification and sulfation in the Golgi apparatus, the HA precursor sugars UDP-glucuronic acid and UDP- N-acetylglucosamine are transported from the cytoplasm to the plasma membrane for further processing without sulfation, which leads to the production of HA. The noteworthy exception to the following steps in GAG biosynthesis is hyaluronic acid (HA). These UDP-activated sugars are then transported from the cytoplasm to the Golgi apparatus through an antiporter transmembrane transporter for further modification. These sugars include UDP-glucuronic acid, UDP- N-acetylglucosamine, UDP-xylose, UDP-galactose, and UDP- N-acetylgalactosamine. The process of GAG biosynthesis begins in the cellular cytoplasm with the synthesis of five uridine diphosphate (UDP) derived activated sugars. It is important to note that unlike proteins and nucleic acids, GAG biosynthesis is a non-template driven process that occurs through the combined action of several tissue-specific enzymes. This section will provide an overview of the cellular mechanisms involved in GAG biosynthesis. The cellular organelles involved in the synthesis and modification of GAGs to their final, bioactive structure are numerous and differ based on the unique GAG synthesized. ![]() This activity will provide a summary of the molecular structures and resulting physiologic functions of the four primary groups of GAGs. The four primary groups of GAGs are classified based on their core disaccharide units and include heparin/heparan sulfate, chondroitin sulfate/dermatan sulfate, keratan sulfate, and hyaluronic acid. Some of these processes include regulation of cell growth and proliferation, promotion of cell adhesion, anticoagulation, and wound repair, among many more. However, evidence now suggests that GAGs play a key role in cell signaling, which serves to modulate a vast amount of biochemical processes. ![]() Historically, the function of GAGs was thought to be limited to cell hydration and structural scaffolding. Their functions within the body are widespread and determined by their molecular structure. They are composed of repeating disaccharide units that are present in every mammalian tissue. Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are negatively-charged polysaccharide compounds.
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