STRUCTURE AND PROPERTIES OF BIOMOLECULES - A. E. Zemlyakov - 2017

16. LIPIDS: LIPID COMPLEXES AND BIOLOGICAL MEMBRANES

❖ Micelles — the simplest aggregates formed by Lipids in the bulk phase of a solvent. Depending on the polarity of the solvent, regular micelles or inverted ("reverse") micelles are formed.

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Lipids with a bulky and/or charged polar HEAD and relatively short hydrocarbon chains, such as gangliosides or dioctanoylphosphatidylcholine, readily form micelles in Water. One of the driving forces behind micellization is the system's tendency to minimize hydrophilic-hydrophobic interactions.

An important property of micelles is their ability to solubilize (dissolve) substances that are otherwise insoluble in a given medium. For instance, regular micelles can incorporate fat-soluble substances such as vitamin A.

❖ Lipid bilayers. Lipids that do not form micelles aggregate in an aqueous bulk phase into a bimolecular layer 4-5 nm thick. In this arrangement, the polar head groups of the lipids contact water, while the hydrophobic hydrocarbon "tails" form a nonpolar core. Bilayers are most characteristic of lipids whose polar and nonpolar cross-sectional areas are comparable, such as Phospholipids.

At low water content (up to 40%), the system is homogeneous and exhibits a layered (lamellar) Structure. When the aqueous phase is increased, closed mono- or multilamellar structures known as Liposomes are formed. Like micelles, liposomes can entrap various BIOLOGICALLY ACTIVE SUBSTANCES and provide targeted delivery into Cells.

❖ Molecular Organization of Introduction/36.html">Biological Membranes. As early as the first half of the 20th century, it was established that biological membranes are Complexes of Proteins and lipids. Several models for the mutual arrangement of these components within the membrane were proposed, but they were refuted by experimental data.

In 1972, American researchers S. Singer and G. Nicolson proposed the "fluid-mosaic" model of Biomembranes, which, with certain modifications, is currently considered universally accepted. According to this model, The basis of the lipid membrane consists of phospholipids and sterols forming a biomolecular layer.

Phospholipids contain residues of saturated and unsaturated carboxylic acids. Unsaturated hydrocarbon chains pack less densely against one another, thereby reducing hydrophobic interactions between individual phospholipid molecules and, consequently, increasing lipid mobility.

Proteins are embedded within Cell/29.html">The Lipid Bilayer; some reside on the membrane surface (peripheral proteins), whereas others—integral proteins—span the entire lipid layer.

Integral proteins possess large hydrophobic regions and are therefore strongly bound to the lipid environment. Hydrophilic Amino Acids predominantly form the surface that interacts with the aqueous surroundings.

The interaction of proteins with their lipid surroundings, including sterols and Glycolipids, creates Regions of the lipid membrane with reduced mobility known as microdomains, which float like icebergs in the "lipid sea" of the biomembrane.

Table 12. Major membrane components of various organisms

Many integral proteins function as receptors or Ion Channels, while several Membrane Proteins exhibit enzymatic properties. Integral proteins are typically glycosylated. The oligosaccharide chains of such Glycoproteins, together with glycolipids, form a carbohydrate coat (glycocalyx) on The Cell surface, such as the oligosaccharide determinants On the surface of erythrocytes.

In some regions of the lipid molecule, lipids rotate easily around their own axis and move along the plane of the lipid layer, known as lateral diffusion, whereas in other regions, the lipid components exist in a highly ordered state.

A number of proteins are capable of moving across the membrane surface, while others remain in a fixed position due to interactions with the Cytoskeleton or internal cellular Organelles. The biological properties of membrane proteins typically manifest themselves precisely when they are associated with the biomembrane.

Proteins exhibit absolute Asymmetry in their arrangement on the biomembrane. They are always oriented in a strictly specific manner. This is facilitated both by the aforementioned interaction of hydrophobic amino acids with the lipid layer and by additional stabilization through the incorporation of lipophilic molecules into the protein. The hydrocarbon "tails" of such structures embed themselves into the lipid bilayer and act as "lipid anchors."

Lipids also display asymmetry between the inner and outer leaflets of the membrane—meaning that identical lipids are present at different concentrations.

This lipid asymmetry persists despite the fact that "flip-flop" occurs readily in real membranes—the translocation of a lipid from the outer leaflet to the inner one and vice versa.

The "flip-flop" process is facilitated by specialized membrane proteins known as flippases, which ease the energetically unfavorable transfer of the polar lipid head group across the Hydrophobic core.

❖ Cell wall of mycobacteria. The surface of every cell type has its own distinctive features. It is well known that tuberculosis Bacteria are exceptionally resistant to antiseptic agents, including acids, alkalis, and oxidizing agents. This is largely due to the ORGANIZATION OF THE mycobacterial cell wall. The lipid-protein membrane of this genus of bacteria is covered by a peptidoglycan mesh, to which arabinogalactan chains are attached via phosphodiester bonds (linkers) at muramic acid residues (approximately one in every ten). In this polysaccharide, the galactan core is linked to arabinofuranosyl chains containing blocks of mycolic acids.

On the other hand, lipoarabinomannan (LAM) chains are anchored to the biomembrane via embedded lipid "anchors" consisting of phosphatidylinositol linked to a mannose residue (PIM). Polyprenyl (pPre) sugar derivatives also function as lipid "anchors." Thus, a robust carbohydrate shell is formed on the cell surface, which is further complemented by a capsular layer of Polysaccharides (glucans, Mannans).

In turn, the highly lipophilic residues of mycolic acids are capable of retaining surface glycolipids—including TDM—as well as hydrophobic proteins through hydrophobic interactions. This forms a second lipid layer that differs in structure from the phospholipid bilayer.

❖ Transport across membranes. One of the primary Functions of biomembranes is to mediate the selective transport of various substances, including ions. For virtually all compounds, with the exception of water molecules and certain other low-molecular-weight products, free transport (simple diffusion) across the membrane is impossible. Specialized structures known as channel proteins exist on the cell surface to facilitate specialized substance transport. Ionotropic receptors, which function as ion channels, were discussed earlier.

Aquaporins serve as another example of proteins involved in membrane transport. These integral membrane proteins allow water molecules to pass into the cell while blocking larger molecules and ions. Certain aquaporins also mediate The transport of ammonia, carbon dioxide, and glycerol molecules.

For the discovery of aquaporins, American professor P. Agre was awarded the Nobel Prize in Chemistry in 2003.

Ion transport mediated by specialized compounds—ionophores and channel-forming Antibiotics—has been extensively studied using model membranes.

✵ Ionophores are specific molecules or molecular assemblies that form complexes with ions on one side of the membrane, transport them across the lipid layer in this complexed form, and subsequently release the ions. Such substances are also referred to as "carriers."

The best-known "carrier" is the cyclic peptide valinomycin. Its structure contains three blocks consisting of D- and L-valine and two hydroxy acids: L-lactic acid (Lac) and D-2-hydroxy-3-methylbutyric acid (Hmb).

The dimensions of the internal cavity correspond to the radius of the potassium ion, which is coordinated by the oxygen atoms of the ester carbonyl groups. This is accompanied by high selectivity for the cation. The Stability of the complex with the potassium ion is many times higher than that with the sodium ion.

In a non-polar environment, due to six intramolecular Hydrogen Bonds (C=O…H-N), the molecule adopts the conformation of a bulky letter S. Upon coordination with a potassium ion, the molecular conformation changes, shielding the internal ion. In this form, the molecule easily crosses the lipid layer. In a polar aqueous phase, the molecule assumes an “open” shape, releasing the K⁺ ion.

✵ Channel-forming antibiotics. A number of peptide antibiotics, such as gramicidin A, are capable of forming a channel in the bilayer membrane through which ions can pass. Structurally, gramicidin A is a linear pentadecapeptide with blocked N- and C-termini.

Two Types of channel architecture are possible: two molecules form an antiparallel double helix, as demonstrated by models in organic Solvents, or two gramicidin A molecules form a helix by joining “head-to-head”. The latter option is realized in lipid membranes.

Within cells, channels are formed as complex assemblies of channel-forming antibiotic molecules and sterols. Such channels are permeable not only to water and ions, but even to small neutral molecules like glucose.

Control Tasks

Test 5 (Option)

1. Write the structural formula of adenosine 5'-triphosphate.

2. Write the structural formula of oleic acid.

3. Determine the name of the given compound and identify the lipid group to which it belongs.

I. N-oleoylsphingosine; II. N-linoleoylsphingosine; III. nervon; IV. globoside; V. cholesteryl palmitate; VI. ergosteryl palmitate; VII. phosphatidylcholine; VIII. phosphatidylserine; IX. phosphatidylinositol; X. ceramide phosphocholine; XI. 1-O-palmitoyl-sn-glycerol; XII. 3-O-palmitoyl-sn-glycerol

A. glycerolipids; B. Waxes; C. sterols; D. phospholipids; E. sulfolipids; F. glycolipids; G. Sphingolipids.

4. Match the pairs:

A. codon; B. exon; C. intron; D. promoter; E. terminator.

I. a DNA region where METABOLISM/31.html">Transcription begins; II. a DNA region where transcription halts; III. a DNA sequence consisting of three NUCLEOTIDES; IV. a Gene region encoding Protein Synthesis; V. non-coding DNA regions.

5. Arrange the letter designations of substances and processes in accordance with their positions in the transcription diagram:

A. terminator; B. promoter; C. factor; D. mRNA; E. DNA; F. ATP, GTP, CTP, TTP; G. ATP, GTP, CTP, UTP; H. transcriptase.

6. Identify the name of the presented compounds

1. myricyl palmitate; 2. Cholesterol; 3. stigmasterol; 4. ergosterol; 5. sphingosine; 6. thymidine; 7. ribothymidine; 8. uridine; 9. pseudouridine; 10. deoxycytidine; 11. deoxyadenosine; 12. deoxyguanosine.