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Biological synthesis of Hyaluronic acid

Views: 11     Author: Site Editor     Publish Time: 2023-02-08      Origin: Site

Hyaluronan is synthesized by a class of integral membrane proteins called hyaluronan synthases,of which there are three types in vertebrates:HAS1, HAS2, and HAS3.These enzymes prolong hyaluronic acid by repeatedly adding D-glucuronic acid and N-acetyl-D-glucosamine to nascent polysaccharides as it passes through the cell membrane via the ABC transporter into the extracellular space.The term fascia is used to describe the fibroblast-like cells that synthesize HA.Hyaluronic acid synthesis has been shown to be inhibited by 4-methylumbelliferone (hymecromone),a 7-hydroxy-4-methylcoumarin derivative.This selective inhibition (without inhibition of other glycosaminoglycans) may help prevent metastasis of malignant tumor cells.When tested in cultured human synovial fibroblasts,low molecular weight hyaluronan (<500 kDa) feedback inhibited hyaluronan synthesis at high concentrations,but high molecular weight hyaluronan ( >500 kDa) stimulate hyaluronan synthesis.The bacterium Bacillus subtilis was recently genetically modified to be cultured to produce a proprietary formulation of hyaluronic acid,in a patented process to produce a human-grade product.

Fasciacyte hyaluronic acid,

Fascia cells are biological cells that produce a hyaluronic acid-rich extracellular matrix and regulate the sliding of muscle fascia.Fascia cells are fibroblast-like cells found in fascia.They are round,have rounder nuclei, and have fewer elongated cell processes than fibroblasts.Fascial cells aggregate along the upper and lower surfaces of the fascial layers.Fascial cells produce hyaluronic acid, which regulates fascial sliding.

Biosynthetic mechanism

Hyaluronic acid (HA) is a linear glycosaminoglycan (GAG), an anionic gel-like polymer found in the extracellular matrix of vertebrate epithelium and connective tissue.It is part of a family of linear anionic polysaccharides with a complex structure.The presence of carboxylate groups in the molecule makes it negatively charged so that it can successfully bind water and makes it valuable for cosmetics and pharmaceuticals.HA consists of repeating β4-glucuronic acid (GlcUA)-β3-N-acetylglucosamine (GlcNAc) disaccharides and is synthesized by hyaluronan synthase (HAS), a class of integral membrane Proteins that produce well-defined, uniform chain lengths.There are three types of HAS in vertebrates: HAS1,HAS2, and HAS3; these all contribute to the elongation of HA polymers.To create HA capsules,this enzyme must be present because it polymerizes UDP sugar precursors into HA.HA precursors are synthesized by first phosphorylating glucose with hexokinase,yielding glucose-6-phosphate, the major HA precursor.Then,two routes were used to synthesize UDP-n-acetylglucosamine and UDP-glucuronic acid,and the two reacted to generate HA.Glucose-6-phosphate is converted to fructose-6-phosphate by hasE (phosphoglucose isomerase) or to glucose-1-phosphate by pgm (alpha-phosphoglucomutase),both undergoing different reactions.UDP-glucuronic acid and UDP-n-acetylglucosamine are joined together by hasA (HA synthase) to form HA.

Synthesis of UDP-glucuronic acid

UDP-glucuronic acid is converted from glucose-1-P to UDP-glucose by hasC (UDP-glucose pyrophosphorylase),which is then reacted with hasB (UDP-glucose dehydrogenase) to form UDP-glucuronic acid.

Synthesis of N-acetylglucosamine

The forward pathway from fructose 6-P utilizes glmS (amidotransferase) to form glucosamine 6-P,glmM (mutase) then reacts with this product to form glucosamine-1-P.hasD (acetyltransferase) converts this to n-acetylglucosamine-1-P, and finally, hasD (pyrophosphorylase) converts this product to UDP-n-acetylglucosamine.

Two disaccharides form hyaluronic acid

UDP-glucuronic acid and UDP-n-acetylglucosamine combine to form HA through hasA (HA synthase) to complete the synthesis.


Hyaluronic acid can be degraded by a family of enzymes called hyaluronidases.In humans,there are at least seven types of hyaluronidase-like enzymes,several of which are tumor suppressors. Hyaluronan degradation products,oligosaccharides and very low molecular weight hyaluronan have pro-angiogenic properties.Furthermore, recent studies have shown that hyaluronan fragments, rather than natural high-molecular-weight molecules,can induce inflammatory responses in macrophages and dendritic cells in tissue injury and skin grafts.Hyaluronan can also be degraded by non-enzymatic reactions.These include acidic and alkaline hydrolysis, sonication, thermal decomposition and oxidant degradation.


Hyaluronic acid is derived from hyalos (Greek for vitreous,meaning "glassy") and uronic acid because it was first isolated from the vitreous humor and has a high uronic acid content.The term hyaluronate refers to the conjugate base of hyaluronic acid.Since the molecule normally exists in the body as a polyanion,it is most commonly referred to as hyaluronan.