# Lecture 1: Introduction to Biochemistry and the Cell ## Biochemistry --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Define biochemistry and explain its relationship to biology, chemistry, and medicine 2. Describe the hierarchy of biological organization from atoms to organisms 3. Identify the major classes of biological macromolecules and their monomeric units 4. Describe the structural and functional features of prokaryotic and eukaryotic cells 5. Explain the role of water and carbon chemistry in biological systems 6. Describe the major organelles and their biochemical functions --- ## Lecture Content ### I. What Is Biochemistry? Biochemistry is the study of the chemical processes and substances that occur within living organisms. It bridges the gap between chemistry and biology, drawing on principles of organic chemistry, physical chemistry, and physics to explain biological phenomena. The central goal of biochemistry is to understand life at the molecular level, including how molecules interact to produce the properties of living cells, how metabolic pathways are regulated, and how genetic information flows from DNA to RNA to protein. The clinical relevance of biochemistry cannot be overstated, as nearly all diseases have a biochemical basis. Diabetes involves defects in insulin signaling and glucose metabolism. Cancer arises from disruptions in cell cycle regulation and signal transduction. Genetic disorders frequently result from enzyme deficiencies or protein misfolding. A strong understanding of biochemistry is therefore essential for any student of medicine. ### II. The Chemical Basis of Life Living organisms are composed of a relatively small number of elements. The major elements -- carbon, hydrogen, oxygen, nitrogen, sulfur, and phosphorus -- make up approximately 97% of body mass. Trace elements such as iron, zinc, copper, manganese, cobalt, iodine, and selenium are present in much smaller quantities but serve essential roles as enzyme cofactors and structural components. Carbon is the backbone of biological molecules because it is tetravalent, meaning it can form four stable covalent bonds. This allows carbon to create chains, rings, and branched structures, enabling enormous structural diversity. The key functional groups in biochemistry include the hydroxyl group (-OH), found in alcohols and sugars, which is polar and forms hydrogen bonds; the carboxyl group (-COOH), found in amino acids and fatty acids, which is acidic; the amino group (-NH2), found in amino acids, which is basic; the phosphoryl group (-PO4), found in nucleotides and ATP, which is highly charged; the sulfhydryl group (-SH), found in cysteine, which can form disulfide bonds; and the carbonyl group (C=O), found in the aldehyde and ketone forms of sugars. A comprehensive diagram showing the six major functional groups in biochemistry. Panel A: Each functional group drawn with its chemical structure, name, charge at physiological pH, and an example biomolecule containing it. Panel B: A simple organic molecule (such as an amino acid) with arrows pointing to each functional group present, labeled with its properties. ### III. Major Classes of Biological Macromolecules There are four major classes of biological macromolecules, each built from smaller monomeric units. **Proteins** are polymers of amino acids linked by peptide bonds, and they serve a remarkable variety of functions including catalysis (as enzymes), structural support, transport, signaling, and defense. **Nucleic acids** are polymers of nucleotides joined by phosphodiester bonds. DNA stores genetic information, while RNA transfers that information and can also play catalytic roles as ribozymes. **Carbohydrates** are polymers of monosaccharides connected by glycosidic bonds and function in energy storage (glycogen and starch), structural support (cellulose and chitin), and cell recognition. **Lipids** are not true polymers but are assembled from components such as fatty acids and glycerol. They serve critical roles in membrane structure, energy storage, and signaling through steroid hormones, with hydrophobic character being their unifying feature. These macromolecules are assembled through condensation (dehydration synthesis) reactions that release water, and they are broken down by hydrolysis, which consumes water. A four-panel figure showing the four classes of biological macromolecules. Panel A: Amino acids linked by peptide bonds forming a polypeptide. Panel B: Nucleotides linked by phosphodiester bonds forming a nucleic acid strand. Panel C: Monosaccharides linked by glycosidic bonds forming a polysaccharide. Panel D: Fatty acids esterified to glycerol forming a triglyceride. Each panel includes monomer structures, bond types, and water molecules released during condensation. ### IV. The Cell: The Fundamental Unit of Life All living organisms are composed of cells, and there are two fundamental cell types. #### Prokaryotic Cells Prokaryotic cells lack a membrane-bound nucleus and instead house their DNA in a nucleoid region that is not enclosed by a membrane. They are generally smaller, ranging from 1 to 10 micrometers, and include bacteria and archaea. Key features of prokaryotic cells include a cell wall (composed of peptidoglycan in bacteria), a plasma membrane, 70S ribosomes (consisting of 30S and 50S subunits), and the absence of membrane-bound organelles. Their chromosome is typically circular and often accompanied by plasmids. #### Eukaryotic Cells Eukaryotic cells possess a membrane-bound nucleus and are generally larger, ranging from 10 to 100 micrometers. They are compartmentalized by internal membrane systems and include animal, plant, and fungal cells. Each organelle carries out specific biochemical functions. The **nucleus** is the site of DNA replication, transcription, and RNA processing. The **endoplasmic reticulum** comes in two forms: the rough ER, studded with ribosomes, handles protein synthesis and folding, while the smooth ER is responsible for lipid synthesis, detoxification, and calcium storage. The **Golgi apparatus** modifies proteins through glycosylation and handles their sorting and packaging. **Mitochondria** are the powerhouses of the cell, carrying out oxidative phosphorylation, ATP production, and the citric acid cycle. They possess a double membrane, their own DNA (which is maternally inherited), and a highly folded inner membrane called cristae that increases surface area for energy production. **Lysosomes** contain hydrolytic enzymes that function at acidic pH to carry out intracellular digestion. **Peroxisomes** oxidize very long-chain fatty acids and detoxify substances through the enzyme catalase. The **cytoskeleton** provides structural support and facilitates intracellular transport through three types of filaments: microfilaments (actin), microtubules (tubulin), and intermediate filaments. Finally, **ribosomes** (80S, composed of 40S and 60S subunits) are the molecular machines that carry out protein synthesis. A labeled cross-section of a eukaryotic animal cell showing all major organelles. Each organelle is color-coded with a callout box listing its primary biochemical function. The mitochondrion is shown with an enlarged inset depicting its double membrane structure with cristae and matrix. The endoplasmic reticulum is shown continuous with the nuclear envelope, with ribosomes on the rough ER surface. ### V. The Endosymbiotic Theory Mitochondria (and chloroplasts in plants) are believed to have originated from ancient prokaryotes that were engulfed by ancestral eukaryotic cells. Several lines of evidence support this theory: mitochondria have a double membrane structure, possess their own circular DNA, contain 70S ribosomes similar to those of prokaryotes, replicate by binary fission, and are similar in size to bacteria. The clinical significance of this evolutionary origin is that mitochondrial diseases are maternally inherited, since mitochondria are passed from mother to offspring through the egg cell. ### VI. Levels of Organization in Biochemistry The organization of living systems follows a clear hierarchy. Atoms combine to form small molecules such as water, amino acids, and glucose. Small molecules assemble into macromolecules -- proteins, nucleic acids, polysaccharides, and lipids. Macromolecules come together to form supramolecular complexes such as ribosomes, membranes, and chromatin. These complexes are organized into organelles, which function within cells. Cells organize into tissues, organs, organ systems, and ultimately organisms. At each level of this hierarchy, emergent properties arise that cannot be predicted from the components alone. ### VII. Non-Covalent Interactions in Biochemistry Biological structure and function depend heavily on non-covalent interactions. Although individually weak, these forces are collectively powerful and govern many essential processes. **Hydrogen bonds** form between electronegative atoms (such as oxygen and nitrogen) and a hydrogen atom bonded to another electronegative atom, contributing approximately 2 to 5 kJ/mol each. **Ionic interactions** (electrostatic forces) occur between oppositely charged groups and can contribute approximately 20 kJ/mol in a vacuum, though this is considerably weakened in water. **Van der Waals forces** arise from transient dipole interactions and are important for the close packing of molecules, contributing approximately 0.5 to 1 kJ/mol each. **Hydrophobic interactions** result from the exclusion of nonpolar molecules from water and are a major driving force for protein folding and membrane formation. Together, these non-covalent forces govern protein folding and stability, DNA double helix formation, enzyme-substrate binding, and membrane assembly. A comparative diagram showing the four major types of non-covalent interactions in biological systems. Each type is illustrated with a specific molecular example: hydrogen bonds between water molecules, ionic interactions between amino acid side chains (Lys and Asp), van der Waals forces between nonpolar side chains, and hydrophobic effect showing nonpolar molecules clustering in an aqueous environment. Relative bond strengths are indicated with a bar chart on the right side. ---