] BIOCHEMISTRY REVIEW Overview of Biomolecules Deborah W. Louda, Associate Professor Charles E. Schmidt College of Medicine Florida Atlantic University Copyright 2012 Table of Contents Chapter 1: Introduction to Biomolecules…………………………………………………1 Chapter 2: Amino Acids………………………………………………………………….. 4 Chapter 3: Peptides……………………………………………………………………….21 Chapter 4: Protein Sequence……………………………………………………………25 Chapter 5: Protein Conformation………………………………………………………..34 Chapter 6: Enzymes……………………………………………………………………....44 Chapter 7: Carbohydrates………………………………………………………………..57 Chapter 8: Lipids…………………………………………………………………………..84 Chapter 9: Nucleotides…………………………………………………………………...98 Chapter 10: Nucleic Acids………………………………………………………………108 Chapter 11: DNA Replication…………………………………………………………..118 Chapter 12: Transcription……………………………………………………………….135 Chapter 13: Protein Synthesis………………………………………………………….144 Accompanying power point slides are indicated by (PP #). Chapter 1: Introduction to Biomolecules Biochemistry is the study of the chemistry of cells and organisms. Thus it is concerned with the types of molecules found in biological systems, their structure, and their chemical properties. Biochemistry also deals with the function of these molecules, how they interact, and what reactions they undergo. I. Properties of Biomolecules A. General Properties Biomolecules are organic molecules, not fundamentally different from other, typical organic molecules. They are the same types of molecules, react in the same ways, and obey the same physical laws. B. Composition and Structure Biomolecules contain mainly carbon, which behaves as it always does in organic compounds, forming 4 bonds, usually with a tetrahedral arrangement. (PP 2) The carbon skeleton can be linear, branched, cyclic, or aromatic. Other important elements are H, O, N, P and S. About 30 elements are required by biological systems, including iodine and many metals, though most of these are needed in only trace amounts. (PP 3) Biomolecules contain the same types of functional groups as do organic molecules, including hydroxyl groups, amino groups, carbonyl groups, carboxyl groups, etc. (PP 4-5) However, many biomolecules are polyfunctional, containing two or more different functional groups which can influence each other’s reactivity. (PP 6) Biomolecules tend to be larger than typical organic molecules. Small biomolecules have molecular weights over 100, while most biomolecules have molecular weights in the thousands, millions, or even billions. Because of their large size, the majority of biomolecules have specific 3-dimensional shapes. The atoms of a biomolecule are arranged in space in a precise way, and proper arrangement is usually needed for proper function. The 3-dimensional shape is maintained by numerous non-covalent bonds between atoms in the molecule. (PP 7) Because of the weak nature of most non- covalent bonds and because of interactions between the biomolecule and the solvent, the biomolecule’s structure is flexible rather than static. C. Stereochemistry As is common with organic compounds, many biomolecules exhibit stereochemistry. When four different types of atoms or functional groups are bonded to one carbon atom, the carbon is stereogenic (or chiral or asymmetric) and the 1 compound can exist in two different isomeric forms that have different configurations in space. The two configurations are mirror images of each other and are not superimposable. (PP 8) When two compounds are mirror images of each other they are called enantiomers or optical isomers, a subclass of stereoisomers. Enantiomers usually have identical chemical properties, and differ only in the way they rotate plane- polarized light or interact with other chiral compounds. Most biomolecules have several or many asymmetric carbons and so may have many diastereomers, a subclass of stereoisomers that are non-mirror images and have different properties. (PP 9) Stereochemistry is important because biological systems usually use only one specific isomer of a given compound. II. Types of Biomolecules Biomolecules can be divided into several major classes and a few minor classes. A. Amino Acids and Proteins Amino acids are relatively small molecules with molecular weights around 100-200. (PP 10) They are used to produce energy, to synthesize other molecules like hormones, and to make proteins. Proteins are polymers of amino acids. (PP 11) They fold into specific shapes and range in molecular weight from several thousand to over a million. (PP 12) Proteins function as enzymes (which catalyze reactions), structural elements, transport molecules, antibodies, etc. B. Carbohydrates (sugars & starches) The smallest carbohydrates are the monosaccharides with molecular weights of around 100-200. (PP 13) They are a major source of energy for biological systems. Polysaccharides are polymers of monosaccharides with molecular weights often in the millions. (PP 14) Polysaccharides also have definite shapes and serve as structural elements or as stored metabolic energy. (PP 15) C. Lipids (fats & oils) Lipids are relatively small water-insoluble molecules with molecular weights of up to 750-1500. (PP 16) Because they are defined by their water-insolubility, they are chemically more diverse than the other classes of biomolecules, with about half a dozen major types. Lipids are used for energy production and storage, hormones, structural elements of cell membranes, and vitamins. Lipids do not polymerize to form macromolecules, but they can aggregate non-covalently to form very large structures. (PP 17) 2 D. Nucleotides and Nucleic Acids Nucleotides are relatively small molecules with molecular weights in the hundreds. (PP 18) They function in transferring energy and in helping enzymes to catalyze reactions. Nucleic acids (DNA and RNA) are large polymers of nucleotides, with molecular weights up into the billions. (PP 19) They form structures like the double helix, and they function in storing, transmitting, and utilizing genetic information. (PP 20) E. Small Organic Molecules In addition to the major classes of biomolecules, there are many relatively small organic molecules required by cells for very specific functions; these molecules do not fall neatly into one of the above major categories. These molecules can be precursors of biomolecules that help enzymes function (often related to vitamins), or can be intermediates in metabolic pathways, etc. (PP 21) F. Inorganic Ions Though not actually biomolecules, many inorganic ions are required by cells, often in trace amounts. These include calcium, sodium, iron, magnesium, potassium, chlorine, etc. Inorganic ions perform a variety of functions such as structural elements (calcium in bone), regulation of osmotic pressure and transport (sodium), and components of proteins and enzymes (iron). G. Combinations of Biomolecules Sometimes one biomolecule can contain components from two of the major classes, such as a lipoprotein (lipid plus protein) or a glycoprotein (carbohydrate plus protein). 3 Chapter 2: Amino Acids I. Introduction The major function of amino acids is to act as the building blocks of proteins. Amino acids themselves can be used by the cell to produce energy and are the starting point for making many nitrogen-containing compounds. II. General Structure A. Formula As the name implies, amino acids contain two functional groups, a carboxylic acid group and an amino group. The common amino acids are α-amino acids where both functional groups are attached to the same carbon atom. NH2 │ R — C — COOH │ H Also attached to the central carbon are a hydrogen atom and an R group, which is different in each amino acid. The form above is called the non-ionic form. Both the amino group and carboxyl group are capable of ionizing. At neutral pH, which is normal for biological systems, both groups are ionized. (PP 2) + NH3 │ R — C — COO¯ │ H This doubly ionized form is called the zwitterion (hybrid ion with one positive charge and one negative charge) and overall has a zero charge. (PP 3-6) Crystalline amino acids have this structure, and the electrostatic forces between molecules explain the higher-than-expected melting points of amino acids. 4 B. Stereochemistry If the R group is something other than a hydrogen atom, then the central carbon is asymmetric and there will be two enantiomers (mirror images). (PP 7) The compound glyceraldehyde is used as a reference compound for distinguishing stereoisomers. (PP 8) CHO CHO │ │ HO ― C ― H H ― C ― OH │ │ CH2OH CH2OH L – glyceraldehyde D - glyceraldehyde The prefixes L and D stand for levo (rotates light to left) and dextro (rotates light to right). For amino acids COOH COOH │ │ NH2 ― C ― H H ― C ― NH2 │ │ R R L - amino acid D - amino acid It is the L-amino acids that are biologically important, with very few exceptions. Amino acids found in proteins are normally L-isomers. C. Classes There are 20 common or major amino acids that are found in proteins. They are divided into groups based on the nature of the R group. However, not every amino acid falls neatly into a category, so there can be variations in how amino acids are classified. For instance, the glycine R-group is sometimes classified as hydrophilic and sometimes as hydrophobic. Each amino acid can be designated by a three-letter abbreviation, or by a one-letter abbreviation. (PP 9) 1. Nonpolar aliphatic R groups The R group of these amino acids is hydrophobic, but not the entire amino acid. The R groups are mainly hydrocarbon in nature. (PP 10) 5 COO¯ │ + NH3 ― C ― H │ Alanine - Ala, A CH3 COO¯