Lipids to Chemiosmosis PDF

They represent a very heterogeneous class of Lipids substances comprising compounds soluble in organic solvents and not in water In animals, they are used as food (9.3 kcal/ g) and accumulated as reserve material They can be distinguished in: ◼ Saponifiabl...

They represent a very heterogeneous class of Lipids substances comprising compounds soluble in organic solvents and not in water In animals, they are used as food (9.3 kcal/ g) and accumulated as reserve material They can be distinguished in: ◼ Saponifiable lipids (containing a carboxylic group - fatty acids and their esters) ◼ Non-saponifiable lipids (they do not contain a carboxylic group - alcohols, alkanes, 1 terpenes) cell structuring 2  Fatty acids Fatty acids are aliphatic monocarboxylic acids with a variable number of carbon atoms, usually in even numbers, without branches and non- cyclic saturated unsaturated Saturation is referred to hydrogens. When the the aliphatic chain does not present any double bond the fatty acid is considered saturated (of hydrogen atoms) Fatty acids can be divided in three categories Short-chain fatty acids: C4 - C10 O caproic acid CH3(CH2)4C OH Medium-chain fatty acids: C12 - C14 O lauric acid CH3(CH2)10C OH Long-chain fatty acids: C16 - C22 O arachidic acid CH3(CH2)18C OH 4 Double bond position Traditionally the position of the double bonds is numbered starting from the terminal methyl (ω) Unsaturated fatty acids in humans have a "cis" conformation This numbering is justified by the specificity of the desaturases In humans, there is no enzyme capable of forming double bonds in the ω-3 position 5 R groups on the same side R groups on the opposite side Cis double bonds induce peculiar molecular shapes in fatty acids 6 Natural fatty acids They are distinguished in ◼ Saturated ◼ Unsatured ◼ Insaturi 7 The different fatty acids have different melting temperatures 8  1) The presence of cis double bonds results in bent structures. Remember that double bonds are rigid bonds and rotation around them is not allowed. STRONG INTERACTIONS VS WEAK INTERACTIONS Arachidonic acid 2) Differently from unsaturated fatty acids, saturated fatty acids give rise to strong intermolecular interactions. They can align one to HIGH MELTING POINT vs LOW MELTIG POINT the other maximizing the contact. (SOLID) (LIQUID) 9 Lipid composition The appearance of the food is determined by its composition The hydrogenation of unsaturated fatty acids in vegetable oils is performed to produce margarines and alter the macroscopic structure of the fat (it makes it spreadable, extends its storage period) 10  The triacylglycerols or triglycerides Most dietary lipids are fatty acid esters with glycerol forming triacylglycerols Again: nucleophilic acyl substitution! 11  Phospholipids consist of 2 Phospholipids long non-polar chains (tails) and a complex polar head Molecules that have both a hydrophobic and hydrophilic part are called amphipathic 12  Phospholipids The two hydrocarbon tails are formed by carbon and hydrogen atoms. The binding electrons of the CH2 groups are evenly distributed and the structure does not show polarity. The non-polar molecules are unable to interact with water and are excluded from the aqueous phase. The head of the phospholipids displays an electrically charged and polar group capable of interacting effectively with water molecules. They are amphipathic molecules 13 Phospholipids Glycerophospholipids are similar to triglycerides except that one hydroxyl group of glycerol is replaced by the ester of phosphoric acid and another molecule as an amino alcohol, bonded through a phosphodiester bond. 14 Amphipathic molecules self-organize spontaneously The structuring of the water molecules involves a negative variation in the entropy of the system To minimize this effect, the system tends to reduce the contact surface between water and the hydrophobic part of the lipid molecules. This objective can be achieved by making the hydrophobic components aggregate in a single phase (coalescence 15 of the hydrophobic parts).  Amphipathic molecules Detergents, fatty acids and phospholipids have a hydrophilic component (polar head) and a hydrophobic component (non-polar tail) Molecules that have both a hydrophobic and hydrophilic part are called amphipathic 16 If the lipid molecules The shape of the lipid have a bulky polar head and a thin non-polar tail, they self-organize into determines the final micelles structure of the membrane If the lipid molecules have a polar head and an non-polar tail of similar size, they self-organize into double layers 17  Membranes Life is possible because there are structures (membranes) capable of separating the organism from the external world Membranes are used as: Protective barriers of separation with the external environment Systems to form specialized compartments within the cell Systems for regulating the exchange of matter and information between the outside and inside of the cell and between its compartments 18 Membrane structure Intercellular membrane space membrane The cell membrane at the electron microscope consists of two dark structures separated by a less dense component 19  Biological membranes Cell membranes consist mainly of phospholipids They have an average thickness of about 5 nm. Polar heads 5 nm Non-polar hydrocarbon tails Aqueous phase 20  Study of membranes There are numerous instrumental techniques that allow to obtain information on cell membranes A considerable development of our knowledge on membranes is due to the introduction of the freeze- fracture technique 21  Fluid Mosaic The model was proposed by Singer and Nicholson in 1972 Numerous proteins are embedded in the membrane Proteins and lipids are able to move on the membrane plane 22  Membrane proteins Membrane proteins can be classified into: ◼ Extinsic: they are partially immersed in the lipid bilayer ◼ Intrinsic: they are completely immersed in the lipid bilayer 23  Membrane water channels Water can cross the membrane by means of specialized channel proteins: aquaporins 24  Cell membrane allows the movement The proteins present on the membrane represent the elements of recognition for the external environment 25 The biological membrane is a flexible structure The cell membrane is used to promote cell movements Keratinocyte on fibronectin 27  Membrane composition Proteins Lipids Carbohydrates Membrane (%) (%) (%) Erythrocyte 49 43 8 Nuclear 59 35 6 membrane Internal 1 mitochondrial 76 23 membrane Myelin 18 79 3 Membrane of 46 51 3 28 the hepatocyte Cell membranes are asymmetrical and both the lipid and protein composition of the two layers is different. Lipid composition of membranes lipids Erythrocyte Myelin Mitochondria Phosphatidyl 19 % 10 % 39 % choline Phosphatidyl 18 % 20 % 27 % ethanolamine Colesterol 25 % 26 % 3% Glycolipids 10 % 26 % 0% Phosphatidyl 1% 1% 7% 29 inositol  Detergents and some toxins destroy the integrity of the membrane Detergents break down the membrane structure by interacting with both the hydrophobic and hydrophilic parts of lipids Toxins can form pores in the membrane, creating an opening between the cytoplasm and the external environment 30  It is produced by all animal cells, as Cholesterol it is an essential structural component of all animal cell membranes. It is essential to maintain both the structural integrity of the membrane and its fluidity. Cholesterol confers stability to animal cells (without affecting their flexibility) protecting membrane integrity and cell viability, thereby allowing animal cells to change shape and animals to move (unlike bacteria and plant cells, which are limited by their cell wall). 31 Cholesterol The cholesterol molecule has numerous functions within the cell membrane ◼ Immobilizes the first portion of the aliphatic tails by hardening and reinforcing the phospholipid bilayer. This decreases the permeability of the membrane to small molecules (water). ◼ Prevents the crystallization of hydrocarbon tails 32 Membranes in biological systems All living organisms control their biological functions by regulating the absorption and elimination of substances through the membranes 33  Partition coefficient The concentration inside the membrane will be different membrane from the concentration in solution depending on the size and polarity of the molecules Cmembrana = Csoluzione β is the partition coefficient solution 34 Permeability depends on the partition coefficient 35 Water freely crosses the membranes Very small, electrically neutral molecules can cross membranes very quickly by simple diffusion Water crosses the membranes much more quickly than can be expected from simple diffusion Electrolytes and larger polar molecules are unable to cross biological membranes 36 Transport across biological membranes There are various ways to transport molecules that do not move freely across cell membranes 37 The protein channels in the membrane Strongly polar or electrically charged molecules that are solvated in solution can not cross lipid membranes The protein channels facilitate the removal of the water molecules and, interacting with the solute, allow its passage. 38 Facilitated diffusion The channel protein resides in the lipid membrane It has access to both sides of the membrane It is selective It can only balance the concentrations on either side of the membrane It is characterized by saturation kinetics 39 Facilitated diffusion 2 The carrier proteins do not extend through the entire lipid bilayer To exert their transport function, they bind reversibly to their molecular cargo and they diffuse through the lipid bilayer Finally, they release the molecular cargo to the other side of the membrane They can only balance the concentrations on either side of the membrane They are characterized by selectivity and saturation 40 kinetics  Comparison between simple diffusion and facilitated diffusion In both types of transport, the net direction of the flow of matter is regulated by the difference in concentration and the net flow stops when the concentrations on the two sides of the membrane are balanced. In simple diffusion the flux is directly proportional to the difference in concentration of the molecule on the two sides of the membrane, while in facilitated diffusion the kinetics follow a saturation trend. 41 Facilitated diffusion kinetics The transport kinetics of facilitated diffusion displays a saturation behavior and it is possible to identify the following parameters:: – Maximum velocity (Vmax) – Affinity constant (Km) transport is subjected to competitive inhibition 42 43  When it is necessary to transport substances against a concentration gradient, active transports are used Primary active transport Secondary active transport – Primary active transport It – It involves the coupling of the involves the use of ATP transport of two substances. which provides energy for The difference in transport concentration of one provides energy for the transport of the other 44  Primary active transport It directly involves the energy obtained from the metabolism (ATP) which is coupled to transport. More than a third of the ATP produced by our body is used to maintain the transmembrane ion concentration gradients ATPasi Na/K It is electrogenic 45 Secondary active transport 1: the antiport It involves the transport of two substances in the opposite direction The difference in concentration of one species is used to promote the transport of the second in the opposite direction The flow of the two substances is coupled 46 Secondary active transport 2: the symport it involves the transport of two substances simultaneously in the same direction The difference in concentration of species is used to promote the transport of the second species in the same direction The flow of the two substances is coupled 47  The absorption of glucose Glucose is absorbed by the intestinal cell through a symport mechanism with the sodium ion Sodium is actively removed from the cell by a pump (ATPase Na / K) in antiport with potassium Glucose is transferred from inside the cell to the blood by facilitated diffusion 48  Phagocytosis and pinocytosis The transport of substances within the cell can take place through very complex mechanisms that involves the use of specialized membrane recognition structures Endocytosis (phagocytosis and pinocytosis) is used for large particles that cannot cross cell membranes 49 Exocytosis The cell is able to secrete substances through a complex mechanism that involves the recognition of membranes 50 ATP Synthesis (Chemiosmosis) The synthesis of ATP is performed by a particular protein complex (ATP synthase or F0F1 complex) on the inner membrane of the mitochondrion which exploits the different concentration of H+ ion between the inside and outside of the mitochondrion 51