Sialic Acids
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About Sialic Acids
These are a fascinating group of alpha-keto acid glycans (see SNFG symbol) with a nine-carbon backbone that has about 80 derivatives containing various functional groups, such as acetyl, glycolyl, and hydroxyl groups, which can vary among different types of sialic acids (see: Schauer R, and Kamerling JP., 2018). Neu5AC, Neu5Gc, and KDN (Keto-3-deoxy-D-glycero-D-galacto-nononic acid) are the three basic forms. Among those, N-Acetyl-D-Neuraminic Acid (Neu5Ac) is more common among animal kingdom. Humans lack the sialic acid N-glycolylneuraminic acid (Neu5Gc) due to a mutation in the CMAH gene (Chou, H...Varki, 2002), which encodes the enzyme responsible for converting N-acetylneuraminic acid (Neu5Ac) into Neu5Gc. This mutation is estimated to have occurred over 2 million years ago in our evolutionary lineage. As a result of this loss, humans often develop antibodies against Neu5Gc, which can lead to immune reactions in xenotransplantation when traces of Neu5Gc are incorporated from dietary sources (Tector, et. al., 2020). Neu5Ac, also known as NANA, is one of the ten monosaccharides that forms glycocode in humans. Here are some key points about them:
Physical chracteristics:
Solubility
- Water Solubility: Sialic acids are generally soluble in water due to their polar nature, which allows them to interact with other biomolecules in the aqueous environment of cells.
Charge
- Negative Charge: At physiological pH, sialic acids carry a negative charge due to their carboxyl group. This charge plays a crucial role in cell-cell interactions and helps create a repulsive force between cells, influencing processes like immune response and cell adhesion.
Anomeric Forms
- Alpha and Beta Forms: Sialic acids can exist in alpha and beta anomeric forms, with the beta form being predominant in solution (over 90%). This structural variation can affect their interactions with other molecules.
Stereoisomeric Forms
- Neu5Ac exist as D- isomeric form. In fact, all of the ten monosaccharides that form glycocode exist as D- isomer except Fucose that exist as L-isomer.
Location: They are typically found at the terminal ends of glycoproteins and glycolipids on cell surfaces, playing crucial roles in cellular interactions. These are quite abundant in humans, playing crucial roles in various biological processes.
Key Locations
- Brain: The highest concentration of sialic acids is found in the brain, where they are vital for neural transmission and the structure of gangliosides, which are important for synaptic function.
- Blood: Sialic acids are present in blood plasma, primarily bound to glycoproteins like orosomucoid and transferrin. They help stabilize these proteins and contribute to immune responses.
- Milk: Human breast milk contains significant amounts of sialic acids, which are believed to support infant brain development and immune function.
Functions:
- Cell Recognition: This glycan helps cells communicate and recognize each other, which is vital for immune responses and tissue development.
- Pathogen Interaction: Some bacteria and viruses exploit host sialic acids to evade the immune system or facilitate infection. For example, influenza viruses bind to sialic acids on host cells to initiate infection.
- Cancer: Tumor cells often overexpress sialic acids, which can help them evade immune detection.
Because of these, analogs of Sialic acid are drawing great attentions as a glycan-based drug candidate (Vocadlo, et. al., 2022; WißfeldJannis, et. al., 2024)
Health Implications:
- Brain Development: Sialic acids are important for neural function and development. They are abundant in the brain and play roles in synaptic transmission.
- Dietary Sources: Humans cannot synthesize certain types of sialic acids, like N-glycolylneuraminic acid (Neu5Gc), but can incorporate them from dietary sources.
Metabolism
- Biosynthesis: Sialic acids are synthesized from precursors like N-acetylmannosamine and phosphoenolpyruvate.
- Degradation: They can be broken down by enzymes called sialidases, which remove sialic acid residues from glycoproteins.
Common Linkages with other glycans:
- α2,3 Linkage: This is where sialic acid is linked to the C2 position of a galactose (Gal) residue. This linkage is common in many glycoproteins and glycolipids.
- α2,6 Linkage: Here, sialic acid is attached to the C6 position of galactose (Gal) or N-acetylgalactosamine (GalNAc). This linkage is often found in N-linked glycans.
- α2,8 Linkage: This involves sialic acid linking to another sialic acid, forming polysialic acid, which is important in neural cell adhesion and signaling.
Importance of Linkages
The type of linkage affects the biological function and recognition of the sialylated glycans. For instance, different linkages can influence how cells interact with each other and how pathogens recognize host cells.
See other glycans in the human glycocodes.