Unit 2. Molecules and membranes PDF

Unit 2. Molecules and membranes. SECTION I: INTRODUCTION. INDEX 2.1. Cell molecules Carbohydrates Lipids Nucleic acids Proteins 2.2. Cell membranes Membrane lipids Membrane proteins Transport across cell membranes Of the elements found in the human body, f...

Unit 2. Molecules and membranes. SECTION I: INTRODUCTION. INDEX 2.1. Cell molecules Carbohydrates Lipids Nucleic acids Proteins 2.2. Cell membranes Membrane lipids Membrane proteins Transport across cell membranes Of the elements found in the human body, four of them make up the largest percentage of our body weight (96.2%): oxygen, hydrogen, carbon, nitrogen 2.1 Cell molecules Cells are complex and varied structures, capable of replicating and performing a wide range of specialized tasks in multicellular organisms. Cells are basically composed of three fundamental elements: Water Inorganic ions Organic molecules (containing carbon) WATER It represents 70% (or more) of the cell mass. Polar molecule, where H atoms have a slightly positive charge and O slightly negative. This characteristic allows it to form hydrogen bonds with each other and with other polar molecules, or interact with positively or negatively charged ions. Nonpolar molecules tend to minimize their contact with water by being As a result: ions and polar molecules are closely related to each other. easily soluble in water (hydrophilic), while non-polar molecules are poorly soluble in aqueous medium (hydrophobic). INORGANIC IONS They represent 1% (or less) of the total mass of the cell. They are involved in numerous aspects of cellular metabolism and play an important role in some cellular functions. ✓Na+, sodium ✓HPO42-, monohydrogen phosphate ✓K+, potasium ✓Cl-, chlorine ✓Mg2+, magnesium ✓HCO3-, bicarbonate ✓Ca2+, calcium ORGANIC MOLECULES 4 types: carbohydrates, lipids, proteins and nucleic acids. These macromolecules make up more than 90% of the dry weight of most cells. The rest of the mass is made up of molecules of small molecular size, including the precursors of these macromolecules. Proteins, nucleic acids, and most carbohydrates (polysaccharides) are macromolecules formed by the polymerization of hundreds or thousands of low molecular weight precursors: amino acids, nucleotides, or simple sugars, respectively. Carbohydrates Simple sugars (monosaccharides). Main nutrients of cells. Its degradation provides not only the source of energy, but also the starting material for the synthesis of other cellular compounds. Polysaccharides. They are energy storing sugars and are structural components of the cell. In addition, polysaccharides and other shorter polymers of sugars act as markers for a variety of cell recognition processes, including inter-cell adhesion, and the transport of proteins to appropriate intracellular destinations. MONOSACCHARIDES The basic formula of monosaccharides is: (CH2O)n, where n is the number of carbon atoms that make it up. From this formula comes the name of carbohydrate [C = 'carbo' and H2O = 'hydrate']. Glucose (6C) sugar is especially important in cells, as it is the main source of energy. Other simple sugars have between 3 and 7 carbons, with 3 to 5 carbons being the most common sugars.  Sugars with 5 or more carbons can be cyclized to form ring structures, which are the predominant forms within cells. Cyclized sugars exist in two forms: a and b, depending on the configuration of C1.  Monosaccharides can be linked to each other through dehydration reactions, where a molecule of water is removed and the two sugars are linked by a glycosidic bond between two carbon atoms. If only a few sugars are attached, the resulting polymer is called an oligosaccharide. Polymers of hundreds or thousands of glycosidic bond sugars are called polysaccharides.  Glycogen and starch: most common polysaccharides. They constitute the storage forms of carbohydrates in the cells of animals and plants respectively. Composed of glucose molecules in a configuration. The glycosidic bond occurs between the C1 of one glucose and the C4 of another. Occasionally, these polysaccharides contain a(1 → 6) bonds, in which the C1 of one glucose binds to the C6 of another, so that two independent chains a(1 → 4) join (branches). Starch is a macromolecule made up of two polysaccharides, amylose and amylopectin (1: 3 ratio). Only amylopectin has branches a(1 → 6).  amylopectin (starch) glycogen More branches  Cellulose, in contrast, has a well-defined function as the main structural component of the cell wall of plant cells. Composed of glucose molecules. The glucose residues have a b -conformation and is not a branched polysaccharide. The union of the glucose residues is carried out by b(1 → 4) bonds that make the cellulose form long chains that are packed together to form fibers of great mechanical strength. Other functions of carbohydrates: Cell signaling. Bound to proteins they function as markers to direct proteins to the cell surface or to join various cell organelles. As markers on the cell surface. Playing important roles in cell recognition and interactions between cells in multicellular tissues. Lipids They perform fundamental functions in cells: 1. Energy source. 2. Main component of cell membranes. 3. Cell signaling: - steroid hormones (estrogens, testosterone) - molecular messengers that carry signals from receptors to molecular targets within cells.  The simplest lipids are fatty acids, consisting of long hydrocarbon chains, containing between 16 or 18 C, with a COO- carboxyl group at the end. Long hydrocarbon chains of fatty acids contain only nonpolar C-H bonds, which are unable to react with water. Its hydrophobic nature is responsible for the behavior of complex lipids, in particular for the formation of biological membranes.  Fatty acids are stored in the form of triglycerides or fats, which consist of three molecules of fatty acids, linked with one molecule of glycerol. Triglycerides are insoluble in water and accumulate as a fat drop in the cytoplasm. When necessary, they are degraded for use as energy precursor molecules. More efficient storage than carbohydrates, producing more than twice the energy, per weight of degraded material. They allow energy to be stored in less than half the body weight that would be required to store the same amount of energy with carbohydrates, which is very important since it allows greater mobility of the animals.  Phospholipids are the main components of cell membranes. They are made up of two fatty acid molecules plus a polar head group consisting of a phosphate group and other polar molecule/s. For this reason, they are amphipathic molecules, partly soluble in water and partly insoluble: they have hydrophobic tails and hydrophilic head groups. Membrane phospholipids are typically phosphoglycerides, in which the two fatty acid molecules are attached to a glycerol molecule and the third carbon of glycerol is attached to the phosphate group. In turn, the phosphate group can bind to another small polar molecule (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, or phosphatidylinositol). Sphingomyelin: the only non-glyceric phospholipid in cell membranes, the two fatty acid chains are attached to a polar head group consisting of serine instead of glycerol.  In addition to phospholipids, many cell membranes contain glycolipids and cholesterol. Glycolipids are composed of fatty acids linked to polar head groups that contain carbohydrates, so they are also amphipathic. Cholesterol consists of four strongly hydrophobic hydrocarbon rings, but the hydroxyl group (OH) attached to one end of cholesterol is weakly hydrophilic, so it can also be considered amphipathic. Testosterone and estradiol are hormones derived from cholesterol that play a fundamental role in intercellular signaling. Nucleic acids They are the main information molecules of cells. Deoxyribonucleic acid (DNA) - a unique role as genetic material. There are different types of ribonucleic acid (RNA): ✓ Messenger RNA (mRNA) carries information from DNA to ribosomes, where it serves as a template for protein synthesis. ✓ Ribosomal RNA (rRNA) and transfer RNA (tRNA) are involved in protein synthesis. ✓ Other forms of RNA are involved in the processing and transport of both RNA and proteins, catalyze various chemical reactions, or regulate gene expression.  DNA and RNA are polymers of nucleotides. Nucleotide: nitrogenous bases (purines or pyrimidines), linked to sugars (2'- deoxyribose in DNA; and ribose in RNA)) phosphorylated at the C-5 of sugars. Purines: adenine, guanine Pyrimidines: cytosine, thymine, uracil  The polymerization of nucleotides to form nucleic acids involves the formation of phosphodiester bonds between the 5'-phosphate of one nucleotide and the 3'-OH of the next.  Oligonucleotides are small polymers that contain only a few nucleotides. The polynucleotides that make up cellular RNA or DNA can contain thousands or millions of nucleotides respectively. A nucleotide chain has one sense, with one end of the chain terminated by a 5'-phosphate group and the other by a 3'-hydroxyl group. Polynucleotides are always synthesized in the 5 '→ 3' direction, adding a nucleotide to the 3'-OH group of the chain in formation. By convention, the RNA and DNA strand is always written in the direction 5’→3’.  Information from RNA and DNA is transmitted by the order of the bases in polynucleotide chains. DNA is a double-stranded molecule, which runs in opposite directions. The bases are found on the inside of the molecule, and the two chains are linked by hydrogen bonds between complementary base pairs. The information contained in DNA and RNA directs the synthesis of specific proteins.  Nucleotides play fundamental roles in other biological processes, for example the ATP (adenosine 5 'triphosphate) molecule, the main form of chemical energy within cells. ATP Some nucleotides such as cAMP function as members of cellular signaling pathways. Proteins The proteins are in charge of 'executing' the tasks defined in the information contained in the nucleic acids. They are the most varied macromolecules. Each cell contains thousands of different proteins that perform a wide range of functions: ✓ They are structural components of cells ✓ Transport and storage of small molecules (e.g. hemoglobin that carries O 2) ✓ Information transmitters between cells (protein hormones) ✓ They provide defenses against infection (antibodies) ✓ Enzymes  Proteins are polymers of amino acids (aa). There are 20 different aa. Every aa. It is composed of a carbon (aC), linked to a carboxyl group (COO-), an amino group (NH3+), a hydrogen atom and a characteristic side chain (R). The specific chemical properties of each aa. are At physiological pH (pH = 7) the amino and defined by the nature of R: carboxyl groups are in ionic form. nonpolar aa: They do not interact with H2O. The chains of these aa. are located inside proteins. polar aa: they have polar groups, such as hydroxyl (OH) or amide groups (O=C- NH2). They are hydrophilic and tend to be on the outside of proteins. basic and acidic aa: they are very hydrophilic and are usually found on the surface of proteins.  aa. are linked by peptide bonds between the a- carboxyl group of an aa and the a - amino group of the following. Polypeptides are linear chains of aa, usually hundreds to thousands. Each polypeptide chain has two distinctive ends, one ending in an amino group (amino or N-terminal end), and the other in a carboxyl group (carboxy- or C-terminal end). The amino acid sequence of a polypeptide is written (by convention) in the same order peptide bond in which it is synthesized: from the N- terminus to the C-terminus.  The defining characteristic of proteins is that they are polypeptides with a specific amino acid sequence. Frederick Sanger in 1953 determined for the first time the complete sequence of a protein, insulin: two polypeptide chains linked by disulfide bonds. Frederick Sanger, 1953  Proteins take on characteristic three-dimensional configurations that are crucial to their function. These settings are determined by their aminoacid interactions, so the shape of proteins is determined by their aa sequence. Christian Anfinsen 1957  The structure of proteins is defined in 4 levels: Primary structure: the sequence of aa. of its polypeptide chain. Secondary structure: regular arrangement of aa. within localized regions of the polypeptide. Two most common shapes: the α helix and the β sheet. Both structures are maintained thanks to the hydrogen bonds between the CO and NH groups of the polypeptide bonds. Tertiary structure: it is the folding of the polypeptide chain as a result of the interactions between the side chains of aa. found in different regions of the primary sequence. Quaternary structure: consists of the interactions between different polypeptide chains in proteins composed of more than one polypeptide. 2.2 Cell membranes Cell membranes separate the interior of the cell from its environment and define the internal compartments of eukaryotic cells. All membranes share the same structural organization: phospholipid bilayers and associated proteins. Proteins are responsible for many specialized functions: small molecule transporters, membrane receptors, interactions between cells in multicellular organisms, electron transport, and oxidative phosphorylation. Membrane lipids Phospholipids: fundamental molecules of all cell membranes. As their fatty acid tails are insoluble in water, phospholipids spontaneously form phospholipid bilayers in aqueous media. These bilayers form a stable barrier between two aqueous media and represent the basic structure of all biological membranes. Lipids constitute 50% of the mass of most cell membranes, although this proportion varies depending on the type of membranes. The proportion in the plasma membranes is approximately 50% lipids and 50% proteins. The membranes of the mitochondria can have up to 75% of their mass in proteins.  Lipid bilayers behave like two-dimensional fluids: individual lipids and proteins can rotate and move in lateral directions. Fluidity is crucial for membrane function and depends on temperature and lipid composition (short chain fatty acid interactions are weaker than longer ones: less rigid and maintain greater fluidity at lower temperatures). Cholesterol plays a fundamental role: It inserts into the lipid bilayer with its polar hydroxyl groups close to the hydrophilic head groups of phospholipids. Its hydrocarbon rings interact with the hydrophobic chains of the fatty acids of phospholipids, reducing mobility and increasing rigidity. However, at low temperatures it maintains fluidity. Membrane proteins Phospholipids provide the structural organization and proteins inserted in the lipid bilayer define the specific functions of the different membranes. These proteins are divided into two types, based on their association with the membrane: i. Integral membrane proteins: embedded in the lipid bilayer. Some go completely through the membrane (transmembrane proteins). The parts that generally pass through the membranes are 20-25 nonpolar aa a- helical regions. Another structure that passes through the membrane is the b-barrel, formed by folding b-sheets into a barrel-like structure. This structure is found mainly in bacteria, chloroplasts and mitochondria. ii. Peripheral membrane proteins: they are not inserted in the membrane but are indirectly associated, generally through interaction with other proteins.  They are amphipathic molecules. Some pass through membranes only once, others multiple times. In eukaryotes, most membrane proteins have been modified by the addition of carbohydrates (glycoproteins) that are exposed on the cell surface and play a fundamental role in cell-to-cell signaling and recognition. Proteins can also be membrane anchored by lipids that are covalently linked to the polypeptide chain. Transport across membranes The selective permeability of biological membranes to small molecules allows the cell to control and maintain its internal composition. Only small uncharged molecules can diffuse freely through the phospholipid bilayer. Larger polar molecules (glucose) or charged ions are unable to diffuse across the plasma membrane.  Some transmembrane proteins can act as membrane transporters for these substances that do not cross the lipid bilayer freely. They are classified into two groups: a. Protein channels: they form pores in the membrane, allowing the passage of molecules of a suitable size and charge. Ion channels allow the passage of inorganic ions such as Na+, K+, Ca2+ and Cl-. The pores formed by these channels are not permanently open; rather, they can be selectively opened or closed in response to extracellular signals, allowing cells to control the movement of ions across the membrane. b. Carrier proteins: selectively bind and transport specific molecules, such as glucose. They undergo conformational changes to facilitate the passage of specific molecules through membranes. PASSIVE TRANSPORT Molecules transported, either through protein channels or thanks to carrier proteins, cross membranes in the energetically favorable direction, determined by concentration and electrochemical gradients. ACTIVE TRANSPORT The molecules are transported in an energetically unfavorable direction. It requires the consumption of energy, in the form of ATP.