N-Acetyl-D-glucosamine: used for the treatment of Osteoarthritis

Introduction

N-Acetyl-D-glucosamine, or glcnac or N-acetylchitosamine, belongs to the class of organic compounds known as acylaminosugars. Chemically, it is an amide between glucosamine and acetic acid. N-Acetyl-D-Glucosamine (N-acetlyglucosamine) is a monosaccharide derivative of glucose. A single N-acetlyglucosamine moiety linked to serine or threonine residues on nuclear and cytoplasmic proteins -O-GlcNAc, is an ubiquitous post-translational protein modification. These are organic compounds containing a sugar linked to a chain through the N-acyl group. O-N-Acetyl-D-glucosamine regulates cellular responses to hormones such as insulin, initiates a protective response to stress, modulates a cell's capacity to grow and divide, and regulates gene transcription.

Biological activity

N-Acetyl-D-glucosamine is an extremely weak basic (essentially neutral) compound (based on its pKa). It exists in all living organisms, ranging from bacteria to humans. In humans, it exists in the skin, cartilage, and blood vessels as a hyaluronic acid component, and bone tissue, cornea, and aorta are components of keratan sulfate. Within humans, N-acetyl-D-glucosamine participates in several enzymatic reactions. In particular, this compound can be biosynthesized from chitobiose through the action of the enzyme Beta-hexosaminidase subunit alpha. In addition, N-acetyl-D-glucosamine can be biosynthesized from chitin through the action of the enzyme chitotriosidase-1. O-N-Acetyl-D-glucosamine modified proteins are involved in sensing the nutrient status of the surrounding cellular environment and adjusting the activity of cellular proteins accordingly. In humans, it is involved in the metabolic disorder called the Salla disease/infantile sialic acid storage disease pathway. Outside of the human body, N-Acetyl-D-glucosamine is found, on average, in the highest concentration within milk (cow). N-Acetyl-D-glucosamine has also been detected but not quantified in peachs. This could make N-acetyl-D-glucosamine a potential biomarker for the consumption of these foods.

Treatment of Osteoarthritis

Glucosamine and N-acetyl-D-glucosamine (GlcNAc) are amino sugars in which the hydroxyl group of glucose at position 2 is substituted by an amino group and acetoamide group, respectively. They are the critical components of glycosaminoglycan polymers (such as chondroitin sulfate and hyaluronan) in articular cartilage. Since they are believed to have a crucial role in forming glycosaminoglycans in cartilage, they have been widely used as alternative medicines or dietary supplements for treating Osteoarthritis (OA). Oral administration of GlcNAc is effective in relieving symptoms of OA without generating any adverse reactions in human clinical studies. Hatano et al. conducted a randomized, double-blind comparative study to evaluate the effects of GlcNAc on OA in 67 untreated patients who presented with mild pain and discomfort in the knee. Subjects were divided into two groups and given 200 ml of normal soy milk or soy milk containing 1,250 mg of GlcNAc once daily for 12 weeks. Assessments of subjective symptoms and range of motion of the knee were performed. The results indicated a significant improvement in knee joint pain and the range of motion of the knee, beginning at 8 weeks after the administration of GlcNAc compared with placebo. Furthermore, blood chemistry and physical examination did not show any adverse clinical reactions of any importance.

[1] Daiki Kubomura. “Effect of N-acetylglucosamine administration on cartilage metabolism and safety in healthy subjects without symptoms of arthritis: A case report.” Experimental and therapeutic medicine 13 4 (2017): 1614–1621.

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