Lipopolysaccharides: the pathway in the body

This page shows the biochemical pathway behind the laboratory value Lipopolysaccharides (LPS / endotoxins): which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Lipopolysaccharides (LPS, endotoxins) are components of the outer envelope of Gram-negative bacteria. When they reach the blood, immune cells recognise them via the receptor TLR4, and the liver captures and modifies them.

The pathway step by step

1. Gram-negative bacteria → Lipopolysaccharide LPS, also called endotoxin, is the main component of this outer envelope. It consists of the fatty lipid A, a sugar core and a long sugar chain. Source 1
2. Lipopolysaccharide → LPS in the blood · Chylomicrons When bacteria die, LPS fragments are released. Some of them pass, together with dietary fat in chylomicrons, from the gut into lymph and blood. Source 2
3. LPS in the blood → LPS + LBP · LBP In the blood, lipopolysaccharide-binding protein (LBP) picks up individual LPS molecules and hands them on to the surface protein CD14. Source 3
4. TLR4-MD-2 → NF-κB MyD88 signalling Via the MyD88 signalling chain, the switch NF-κB is released inside the cell. It moves into the nucleus and has certain genes read there. Source 4
5. NF-κB → Cytokines These genes include messengers such as TNF-α and interleukin-6. They summon further immune cells and switch metabolism over. Source 4
6. LPS in the liver → Inactivated LPS AOAH The enzyme AOAH cuts two of the six fatty chains out of lipid A. Without them, the molecule no longer fits into the pocket of MD-2. Source 5
7. Inactivated LPS → Excretion The liver releases the remnants into the gut with the bile. Another part stays bound to lipoproteins in the blood and is kept harmless there. Source 5

Cofactors in this pathway

• Zinc — Metal centre of the bacterial enzyme LpxC, which carries out an early step of lipid A synthesis Source 6, 1
• Magnesium — Divalent ions such as magnesium bridge neighbouring LPS molecules in the outer envelope Source 7In the ORY catalogue as a laboratory value: Magnesium
• Pantothenic acid — Building block of the acyl carrier protein that supplies the fatty chains for lipid A synthesis Source 1
• Triglycerides (dietary fat) — Form chylomicrons, with which LPS passes from the gut into lymph and blood Source 2In the ORY catalogue as a laboratory value: Triglyzeride
• Lipoproteins (HDL) — Bind LPS in the blood and keep it bound Source 5In the ORY catalogue as a laboratory value: HDL-Cholesterin

Sources

1. Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem 2002 · PubMed 12045108
2. Ghoshal S, Witta J, Zhong J et al. Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res 2009 · PubMed 18815435
3. Schumann RR, Latz E. Lipopolysaccharide-binding protein. Chem Immunol 2000 · PubMed 10608081
4. Park BS, Lee JO. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med 2013 · PubMed 24310172
5. Munford RS. Endotoxemia — menace, marker, or mistake? J Leukoc Biol 2016 · PubMed 27418356
6. Di Leo R, Cuffaro D, Rossello A, Nuti E. Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives. Molecules 2023 · PubMed 37298854
7. Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 2003 · PubMed 14665678

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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