MACROMOLECULES CHAPTERS 2,3 LECTURE 4 1. LIVING ORGANISMS OBEY CHEMICAL AND PHYSICAL LAWS 2. CARBON CONTAINING MOLECULES ARE STABLE 3. FUNCTIONAL GROUPS 4. WATER 5. SYNTHESIS BY POLYMERIZATION 6. CELLS CONTAIN FOUR MAJOR FAMILIES OF MACROMOLECULES What I study: Anti-Tumor Immunity Immune Control of Cancer: B cell activation Antigenic Targets Antigen Processing Trafficking T cell activation Innate immunity Immune evasion of Cancer: T cell Dysfunction APC Dysfunction Cytokine Dysregulation Inflammation Immune cells Breast cancer Infiltration of CD8+ lymphocytes into tumor sites after cancer vaccine Red: anti-CD8 CD8+ cells Before After 1. LIVING ORGANISMS OBEY CHEMICAL AND PHYSICAL LAWS: - It is based overwhelmingly on carbon compounds. - It depends most exclusively on chemical reactions that take place in watery solutions and in the relatively narrow range of temperature and pH. Keeping in this range is called homeostasis. - It is dominated and coordinated by enormous polymeric molecules ? chains of chemical subunits linked end-to-end. The unique properties of these long polymeric molecules enable cells and organisms to grow and reproduce and do all the other things that are characteristic of life. - The chemical processes in cells are tightly regulated. - It is complex; even the simplest cell is vastly more complicated in its chemistry than any other chemical systems known. Some allotropes of carbon: a) diamond b) graphite c) lonsdaleite d?f) fullerenes (C60, C540, C70); g) amorphous carbon h) carbon nanotube 2. CARBON CONTAINING MOLECULES ARE STABLE: - The stability of carbon containing molecules is based on the property of the favorable electronic configuration of each carbon atom in the molecule. - The most significant characteristic of carbon is its tetravalent nature. - Each carbon atom forms covalent bonds with four other atoms; creating, for example, short to long chains or ring compounds. - When only hydrogen atoms are used to satisfy the valence requirements the compounds are called HYDROCARBONS. Hydrocarbons in biology play only modest roles because they are essentially insoluble in water. The exception is found in membranes which are very important to biology and whose interior is a non- aqueous, hydrophobic environment of long hydrocarbon tails of phospholipid molecules. The hydrocarbon tails of phospholipid molecules are 'water-hating.? 3. FUNCTIONAL GROUPS: - Most biological compounds contain atoms of oxygen, nitrogen, phosphorus or sulfur (in addition to carbon and hydrogen). - These are typically part of FUNCTIONAL GROUPS conferring water solubility and chemical reactivity. Common functional groups include carboxyl and phosphorus groups, amino groups, and hydroxyl, sulfhydryl, carbonyl and aldehyde groups. 4. WATER: - Water is important because of its critical role as the UNIVERSAL INORGANIC SOLVENT in biological systems. - It is the most abundant component of cells (It is important to note that some organisms have adapted to be able to survive long periods of desiccation.) - Polarity is the key: temperature stability and cohesive properties. - Water molecules are triangular; not linear; two hydrogen atoms bound to the oxygen at an angle of 104.5 degrees. -The molecule is not charged but the electrons are unevenly distributed. The oxygen at the head is ELECTRO- NEGATIVE (it tends to draw electrons toward it giving the end of the molecule a partial negative charge) leaving the other end with a positive charge around the hydrogen atoms. This charge separation gives the water molecule its POLARITY. THIS IMAGE TELLS YOU WHY IONS DO NOT DIFFUSE (OR HAVE A VERY DIFFICULT TIME) ACROSS MEMBRANES Water molecules are closely associated with ions forming a tight shell around them - WATER IS AN EXCELLENT SOLVENT: The most important property of water is its ability to solubilize polar materials of great variety. Most molecules in cells are polar and interact with water. Polar molecules thus dissolve readily in water and are called HYDROPHILIC such as sugar, organic acids and some amino acids. Non-polar molecules are much less soluble in water and are called HYDROPHOBIC such as lipids and most proteins. M. Zinkova 5. SYNTHESIS BY POLYMERIZATION: - Most cellular structures are made up of ordered arrays of linear polymers, i.e., macromolecules: proteins, nucleic acids, polysaccharides, lipids. - Not all macromolecules are linear, some branching occurs such as in polysaccharides. - Macromolecules are made up of repeating subunits (MONOMERS). For example, glucose in cellulose or glycogen, amino acids in proteins, and nucleotides in nucleic acids. - Monomers are added onto one end of a growing polymer chain. - The subunits are added in a particular order, or sequence. - Macromolecules themselves are used as building blocks for the formation of larger structures. - There are four kinds of macromolecule based on FUNCTION: informational: nucleic acids (DNA, RNA=coding information), proteins (recognition, signals), oligosaccharides (recognition), lipids (signals) storage: polysaccharides (starch, glycogen); lipids (triglycerides) structural: polysaccharides (cellulose, chitin); proteins (cytoskeleton). functional: proteins (enzymes) - Macromolecules are synthesized by stepwise polymerization of monomers. - Generally the stepwise polymerization of similar or identical monomers is as follows: i. Addition of each monomer occurs with the removal of a water molecule = CONDENSATION REACTION. ii. Monomers must be present in an ?activated? form. iii. The synthesis of polysaccharides, proteins, and nucleic acids requires an input of energy. This occurs through the consumption of high-energy nucleoside- triphosphates that activate each monomer before its addition to the growing polymer chain. THESE ARE ANABOLIC REACTIONS ATP and NADH (and NADPH) are the most important of the activated carrier molecules. Activated carriers store energy in an easily exchangeable form: ATP stores energy as a readily transferable chemical group. NADH (and NADPH) stores energy as high-energy electrons. 4. macromolecules typically have an inherent directionality. The two ends of the polymer chain are chemically different from each other. 6. CELLS CONTAIN FOUR MAJOR FAMILIES OF MACROMOLECULES: The composition of a cell (bacterial or animal) A limitless variety of polymers can be built from a small set of monomers (=subunits) a. PROTEINS: We will cover this in the next two lectures b. NUCLEIC ACIDS - Nucleic acids store, transmit, and express genetic information. - DNA (=deoxyribonucleic acid) is the primary repository of genetic information and RNA (=ribonucleic acid) has several roles in the expression of DNA information during protein synthesis (messenger RNA, transfer RNA, ribosomal RNA). - Nucleotides consist of a five carbon sugar, one or more phosphate groups, and a nitrogen-containing aromatic base. The sugar ribose for RNA or deoxyribose for DNA. (note that there is less variety in number of nucleotides than in number of amino acids) -The base may be either a purine or a pyrimidine. - DNA contains the purines adenine (A) and guanine (G) and the pyrimidines cytosine (C) and thymine (T). - RNA also has adenine, guanine, and cytosine but contains the pyrimidine uracil (U) in place of thymine. (nucleoside) (nucleotide) - Nucleotides are the Building Blocks of DNA and RNA - Nucleotides can act as short-term carriers of chemical energy (ATP) and signaling molecules (GTP) -The three phosphates are linked by two phospho- anhydride bonds; hydrolysis of these phosphate bonds releases large amounts of chemical energy - The Double helix consists of two complementary chains of DNA twisted together around a common axis to form a right-handed helical structure that resembles a circular staircase. - The chains are oriented in opposite directions along the helix running in the 5' to 3' direction the other in the 3' to 5' direction (antiparallel). - The two strands are also complementary. That is, each base in one strand forms specific hydrogen bonds with the base in the other strand directly across from it. Each adenine must be paired with a thymine and each guanine must be paired with a cytosine. Phosphodiester bond Photograph 51 The Double Helix: 1953 Rosalind Franklin Xray crystals James Watson and Francis Crick Ovarian Cancer age 37 c. POLYSACCHARIDES - Polysaccharides=organic molecules made of sugars - Play no known informational role in the cell (are involved in cell-cell recognitions) and usually consist of a single kind of repeating unit or an alternating pattern of two kinds. -The major polysaccharide in higher organisms are storage molecules like starch and glycogen and structural like cellulose and chitin. - Monomers are monosaccharides (=single sugar). Most sugars have three and seven carbon atoms. The single most common sugar in the biological world is glucose (C6H12O6). The energy is stored in chemical bonds harvested in cellular respiration. - Disaccharides consist of two monosaccharides linked covalently. * Common disaccharides are maltose (2 glucose), lactose (milk sugar, composed of a glucose and galactose), and sucrose (common sugar, composed of glucose and fructose). - Oligosaccharides consist of seven to ten monosaccahrides - Polysaccharides perform either storage or structural function. *Glycogen is highly branched for example. Glycogen is stored in the liver (source of glucose and to maintain blood sugar levels) and muscles (serves as fuel source to generate ATP). * Starches storage in plants. * Cellulose is the best known example of a STRUCTURAL POLYSACCHARIDE and is found in plant cell walls. More than half of the carbon in higher plants is present in cellulose. Like starch and glycogen, it is a polymer of glucose but the repeating monomer is ß glucose, which has nutritional implications. We do NOT have the enzymes to break these bonds so we can?t go out and eat a tree for nutritional purposes while we can hydrolysis the ? bonds of starch. *So... ? bonds for storage; ß bonds for structure. - Functions of Sugars * Production and Storage of Energy: the monosaccharide glucose is a key energy source for cells. * Mechanical Support: components of the extracellular matrix; cellulose of plant cell walls; chitin of insect exoskeleton and fungal cell wall. * Molecular Recognition: small oligosaccharides can be covalently attached to proteins to form glycoproteins and to lipids to form glycolipids; both glycoproteins and glycolipids are found in cell membranes; the sugar side chains on these molecules are recognized by other cells. Example: Human blood groups, termed A, B, AB and O groups). d. LIPIDS - Most lipids are not formed by the kind of stepwise polymerization. - Lipids constitute a heterogeneous group of cellular components that resemble one another more in their solubility properties than in their chemical structures. - The distinguishing feature is their hydrophobic nature, i.e., they have little (at best) affinity for water but are soluble in nonpolar solvents (chloroform). Some lipids are AMPHIPATHIC having both a polar and nonpolar regions. - Lipids are important for energy storage, membrane structure and specific biological functions (such as transmission of chemical signals into and within the cell=signal transduction). - There are 6 main classes of lipids: fatty acids, triacylglycerols, phospholipids, glycolipids, steroids, and terpenes. i. Fatty acids: Long, unbranched hydrocarbon chain with a carboxyl group at one end. * The FA molecule is amphipathic (the carboxyl group renders one end polar and the hydrocarbon tail is nonpolar). * FAs contain 12 to 24 carbons atoms per chain with 16 and 18 common. Each molecule is generated by the stepwise addition of 2 carbon units. * Because they are greatly reduced they hold more potential energy than other biological molecules; yield a great deal of energy when they are oxidized = good energy storage. * Fatty acids with only single bonds between the carbons are saturated fatty acids because every carbon atom in the chain has the maximum number of hydrogen atoms. Unsaturated fatty acids contain one or few double bonds. As you can see this changes the shape of the molecule. ii. Triacylglycerols (TAG): TAGs are also called TRIGLYCERIDES * TAGs consist of a glycerol molecule and three fatty acids. Glycerol is a 3 carbon alcohol with a hydroxyl group on each carbon. * The main function of TAGs is to store energy and contain mostly saturated fatty acids usually solid or semisolid at room temperature. THESE ARE FATS (butter, lard, oils) * Fats do not mix with water because they have three long nonpolar hydrocarbon tails * An important characteristic of fats is the number of double bonds in fatty acid tails. Unsaturated fats are liquid at room temperature (e.g., vegetable oils). Saturated fats like butter and lard are solid at room temperature (contributes to heart disease). NON POLAR TAILS iii. Phospholipids (PL): PL are important components in cell membranes. -They are the critical bilipid layer structure found in all membranes. iv. Glycolipids (GL): These are derivatives of phospholipids that contain a carbohydrate group instead of a phosphate group. The carbohydrate may contain one to six sugars which are water soluble giving glycolipid an amphipathic nature. * GLs are specialized constituents of some membranes and can be sites for biological recognition of surfaces. v. Steroids: Most common is cholesterol which is found primarily in the membranes. It is the starting point for the synthesis of steroid hormones. Vitamin D is a steroid. * All steriods have the same carbon skeleton made of four linked rings. Steroids differ in what is attached to the rings. vi. Terpenes: Joined together in various combinations to produce Vitamin A, carotenoid pigments, and coenzyme Q. ltorvalds Slide 1
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