Lipid II

Key takeaways

Lipid II belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Lipid II to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Lipid II from memory before moving on to harder problems.

Reference excerpt

Lipid II is a precursor molecule in the synthesis of the cell wall of bacteria. It is a peptidoglycan, which is amphipathic and named for its bactoprenol hydrocarbon chain, which acts as a lipid anchor, embedding itself in the bacterial cell membrane. Lipid II must translocate across the cell membrane to deliver and incorporate its disaccharide-pentapeptide "building block" into the peptidoglycan mesh. Lipid II is the target of several antibiotics.

Synthesis

In peptidoglycan biosynthetic pathway Lipid II is the final intermediate in peptidoglycan synthesis. It is formed when the MurG transferase catalyzes addition of N-acetylglucosamine (GlcNAc) to Lipid I, resulting in a complete disaccharide-pentapeptide monomer with a bactoprenol-pyrophosphate anchor. This occurs on the inside of the cytoplasmic membrane, where the bactoprenol chain is embedded in the inner leaflet of the bilayer. Lipid II is then transported across the membrane by a flippase, to expose the disaccharide-pentapeptide monomer, which is the pentapeptide stem consisting of L-Ala-γ-D-Glu-m-DAP-D-Ala-D-Ala between GlcNAc and N-acetylmuramic acid (MurNAc), for polymerization and cross-linking into peptidoglycan. The remaining bactoprenol-pyrophosphate is then recycled to the interior of the membrane. The essential MurJ flippase, which translocates lipid II across the cytoplasmic membrane, was only published in July 2014, after decades of searching. The discovery remained somewhat controversial as assay results were conflicting; FtsW (EC 2.4.1.129) was proposed as an alternative, but evidence has strongly favored the MurJ side since 2019.

Artificial production A method for artificial production of lipid II has been described. For synthesis of lipid II from UDP-MurNAc pentapeptide and undecaprenol, the enzymes MraY, MurG, and undecaprenol kinase can be used. Synthetic Lipid II analogues are used in experiments studying how it interacts with and binds molecules. Significant quantities of the important peptidoglycan precursor have also be isolated, following accumulation in bacterial cells.

Functions Lipid II acts as a "shuttle carrier" of peptidoglycan building blocks in many bacteria by translocating across the cell membrane to deliver and incorporate its disaccharide-pentapeptide. Polymers of lipid II form a linear glycan chain, catalyzed by the glycosyltransferases of family 51 (GT51). Transpeptidases cross link the chains and form a net-like peptidoglycan macromolecule. The resulting glycopeptide is an essential part of the envelope of many bacteria, estimated to exist at a concentration of less than 2000 molecules per bacterial cell. Lipid II biosynthesis is functional and essential even in organisms without a cell wall like Chlamydia and Wolbachia. It has been hypothesized that maintaining lipid II biosynthesis reflects its role in prokaryotic cell division. In the discovery and mechanism of assembly of pili in gram positive bacteria Lipid II has been implicated as a crucial structural molecule. It anchors the pili during or after polymerization of the pilus components.

Antibiotics Since Lipid II must be flipped outside the cytoplasmic membrane before incorporation of its disaccharide-peptide unit into peptidoglycan, it is a relatively accessible target for antibiotics. These antibiotics fight bacteria by either directly inhibiting the peptidoglycan synthesis, or by binding to lipid II to form destructive pores in the cytoplasmic membrane. Examples of antibiotics that target Lipid II include:

Vancomycin and its synthetic derivatives Ramoplanin Several lantibiotics, including the common food preservative nisin Teixobactin Copsin Human alpha defensins

Binding The D-Ala-D-Ala terminus is used by glycopeptide antibiotic vancomycin to inhibit lipid I- and lipid II-consuming peptidoglycan synthesis; in vancomycin-resistant strains vancomycin cannot bind, because a crucial hydrogen bond is lost. Oritavancin also uses the D-Ala-D-Ala terminus, but in addition it uses the crossbridge and D-iso-glutamine in position 2 of the lipid II stem peptide, as present in a number of Gram-positive pathogens, like staphylococci and enterococci. The increased binding of oritavancin through amidation of lipid II can compensate for the loss of a crucial hydrogen bond in vancomycin-resistant strains, Lantibiotics recognize lipid-II by its pyrophosphate. Lipid II interacts with human alpha defensins, a class of antimicrobial peptides, such as Defensin, alpha 1. The latter has been used to describe and predict binding of synthetic low-molecular weight compounds created as possible therapeutic agents in treating of Gram-positive infections. Penicillin-binding protein 4 exchanges d-amino acids into Lipid II (and Lipid I), acting as a transpeptidase in vitro.

References

External links Lipid+II at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Illustrations

Worked examples

Example 1 — a first encounter with Lipid II

Start with the simplest possible case. Write down what Lipid II claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Lipid II before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Lipid II ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Lipid II

In research: Lipid II appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Lipid II in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Lipid II is common in secondary-school and first-year university syllabi. It links to neighbouring topics Lipids, Prokaryotic cell anatomy, so understanding it makes those chapters shorter.
In everyday life: Look for Lipid II outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Lipid II in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Lipid II means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Lipid II out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Lipid II in simple terms?

Lipid II is a precursor molecule in the synthesis of the cell wall of bacteria. It is a peptidoglycan, which is amphipathic and named for its bactoprenol hydrocarbon chain, which acts as a lipid anchor, embedding itself in the bacterial cell membrane.

Why does Lipid II matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Lipid II?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Lipid II.