lipopolysaccharide core region biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of the core region of bacterial lipopolysaccharides, which contains ten saccharide residues. [ISBN:0198506732]

The lipopolysaccharide (LPS) core region biosynthetic process is a complex and essential pathway in Gram-negative bacteria, responsible for constructing the core oligosaccharide component of LPS. LPS, also known as endotoxin, is a major component of the outer membrane of these bacteria and plays crucial roles in various biological processes, including:

1. **Structure and Integrity:** LPS provides structural integrity to the outer membrane, acting as a barrier against external threats like antibiotics and host immune defenses.

2. **Immune Evasion:** The core oligosaccharide region of LPS interacts with host immune cells, triggering various signaling pathways and influencing the outcome of immune responses. Some bacteria modify their core oligosaccharide structures to evade immune recognition and promote survival within the host.

3. **Virulence:** The LPS core region can contribute to bacterial virulence by facilitating adherence to host cells, promoting invasion, and triggering inflammatory responses.

**The biosynthesis of the LPS core region involves multiple enzymatic steps and can be broadly divided into two stages:**

**Stage 1: Synthesis of the Core Oligosaccharide:**

- The core oligosaccharide is built upon a lipid A backbone, which is anchored in the outer membrane.
- Specific glycosyltransferases add sugar residues in a specific order, forming the core oligosaccharide structure. This structure can vary among different bacterial species.
- The most common core oligosaccharide structure consists of a series of sugars, including KDO (2-keto-3-deoxyoctonate), heptose (heptoses are seven-carbon sugars), and various other sugars.

**Stage 2: Modification and Assembly of the Core Oligosaccharide:**

- Once the core oligosaccharide is assembled, it can undergo further modifications, such as phosphorylation, acetylation, and methylation.
- These modifications can influence the biological properties of the LPS molecule, including its interaction with host immune cells and its contribution to bacterial virulence.
- Finally, the core oligosaccharide is attached to the lipid A backbone, forming the complete LPS molecule.

**Enzymes Involved in LPS Core Region Biosynthesis:**

- **Glycosyltransferases:** Catalyze the addition of sugar residues to the growing core oligosaccharide chain.
- **Kinases:** Add phosphate groups to the core oligosaccharide.
- **Acetyltransferases:** Add acetyl groups to the core oligosaccharide.
- **Methyltransferases:** Add methyl groups to the core oligosaccharide.
- **Other enzymes:** Involved in the synthesis and transport of precursor sugars and other building blocks.

**Regulation of LPS Core Region Biosynthesis:**

- The synthesis of LPS is tightly regulated by various mechanisms, ensuring that the correct amount and structure of LPS are produced under different conditions.
- Environmental cues, such as nutrient availability and the presence of antibiotics, can influence the expression of genes involved in LPS biosynthesis.

**Importance of LPS Core Region Biosynthesis in Medicine:**

- Understanding the LPS core region biosynthetic pathway is crucial for developing new antibiotics and other drugs that target the synthesis and function of LPS.
- Targeting LPS biosynthesis can specifically inhibit the growth of Gram-negative bacteria, without affecting human cells.
- Furthermore, LPS and its core region play a role in various disease processes, including sepsis and inflammatory bowel disease. Understanding the mechanisms underlying LPS biosynthesis can contribute to the development of new therapies for these diseases.'
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Proteins (2)

Compounds (2)