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Semester 1: Cellular Biochemistry
Cell cycle: origin of single cell theory, prokaryotic and eukaryotic cell cycles, molecular basis of cell cycle regulation, cell cycle checkpoints, cyclins and cyclin-dependent kinases, apoptosis
Cell cycle
Origin of single cell theory
Single cell theory postulates that all living organisms originate from a single cell, emphasizing the cell as the fundamental unit of life. This theory emerged from the work of scientists like Schwann and Schleiden in the 19th century, who proposed that all plants and animals are composed of cells. The theory provides a foundation for understanding cellular organization and function.
Prokaryotic cell cycle
Prokaryotic cell cycle involves a simple process of cell division known as binary fission. During this cycle, a prokaryotic cell provides a genetic blueprint for the new cell. The cycle includes stages of DNA replication, cell growth, and cytokinesis, leading to two genetically identical daughter cells.
Eukaryotic cell cycle
Eukaryotic cell cycle is more complex and consists of distinct phases: G1, S, G2, and M. The G1 phase includes cell growth, the S phase involves DNA synthesis, the G2 phase is for preparation for mitosis, and the M phase encompasses mitosis and cytokinesis. This intricate cycle ensures orderly and accurate cell division.
Molecular basis of cell cycle regulation
Cell cycle regulation is a critical process controlled by various molecules, including cyclins and cyclin-dependent kinases (CDKs). These molecules work together to ensure the cell cycle progresses in a timely manner by activating signaling pathways that drive the cycle's phases.
Cell cycle checkpoints
Cell cycle checkpoints are critical control mechanisms that monitor and verify the integrity of a cell's DNA and the completion of key processes before proceeding to the next phase. The major checkpoints are found at G1, G2, and the metaphase stage of mitosis. They prevent the division of damaged or incomplete cells.
Cyclins and cyclin-dependent kinases
Cyclins are regulatory proteins that control the progression of the cell cycle by activating cyclin-dependent kinases (CDKs). Each cyclin is associated with a specific phase of the cycle and its concentration fluctuates throughout the cycle, while CDKs remain constant. The cyclin-CDK complexes phosphorylate target proteins, driving the cell cycle forward.
Apoptosis in the context of the cell cycle
Apoptosis, or programmed cell death, is a crucial mechanism that eliminates damaged or unnecessary cells. It is often linked to the cell cycle as the failure to undergo apoptosis can lead to uncontrolled cell proliferation, contributing to cancer development. The regulation of apoptosis is intricately connected to cell cycle checkpoints, ensuring that cells with irreparable damage do not continue to divide.
Extracellular matrix (ECM) components: fibronectin, laminin, collagen, heparan sulfate, proteoglycans and their roles
Extracellular Matrix (ECM) Components and Their Roles
Fibronectin
Fibronectin is a glycoprotein that plays a significant role in cell adhesion, growth, migration, and differentiation. It serves as a bridge between cells and the ECM, facilitating communication and interaction. Fibronectin forms a network that helps stabilize tissue structure and is crucial during wound healing and tissue repair.
Laminin
Laminin is a key component of the basement membrane, providing structural support to tissues and influencing cell differentiation and migration. It interacts with various cell surface receptors, promoting cell adhesion and influencing cellular behaviors such as growth and survival. Laminin is essential for maintaining the integrity of tissues and is involved in the regeneration process.
Collagen
Collagen is the most abundant protein in the ECM, providing tensile strength and structural support to tissues. It forms fibrils that give strength to various structures, including skin, tendons, and cartilage. Different types of collagen exist, each serving specific functions in tissue architecture and integrity. Collagen also plays a role in wound healing and tissue repair.
Heparan Sulfate
Heparan sulfate is a sulfated glycosaminoglycan found in the ECM and cell surfaces. It participates in cell signaling, influencing various biological processes such as cell proliferation, adhesion, and migration. Heparan sulfate interacts with growth factors and cytokines, modulating their activity and availability to cells, thus playing a crucial role in development and tissue homeostasis.
Proteoglycans
Proteoglycans are composed of a core protein and glycosaminoglycan chains. They contribute to the hydration and resilience of the ECM, allowing it to withstand compressive forces. Proteoglycans play roles in cell signaling, regulating cellular interactions, and maintaining ECM integrity. They are involved in various physiological processes, including development and tissue repair.
Cytoskeleton: microtubules, microfilaments, actin dynamics, myosin and molecular motors, microvilli, pseudopodia, intermediate filaments
Cytoskeleton: microtubules, microfilaments, actin dynamics, myosin and molecular motors, microvilli, pseudopodia, intermediate filaments
Microtubules
Microtubules are hollow tubes made up of tubulin protein subunits. They play crucial roles in maintaining cell shape, intracellular transport, and cell division. Microtubules are dynamic structures that can grow and shrink by adding or removing tubulin dimers. They serve as tracks for the movement of organelles and proteins, powered by molecular motors like kinesin and dynein.
Microfilaments
Microfilaments, also known as actin filaments, are thin strands made of actin protein. They are involved in various cellular processes, including muscle contraction, cell motility, and maintaining cell shape. Actin dynamics, characterized by polymerization and depolymerization, allow cells to rapidly change their shape and move.
Actin Dynamics
Actin dynamics refer to the continuous polymerization and depolymerization of actin filaments. This process is regulated by various actin-binding proteins, which control filament growth, branching, and stability. Actin dynamics are essential for cell movement, division, and signaling.
Myosin and Molecular Motors
Myosin is a motor protein that interacts with actin filaments to produce movement. Myosin's ATPase activity allows it to convert chemical energy from ATP into mechanical work. Myosin plays vital roles in muscle contraction, cytokinesis, and intracellular transport, working in conjunction with microtubule-based motors like kinesin and dynein.
Microvilli
Microvilli are finger-like projections on the surface of some epithelial cells that increase surface area for absorption and secretion. They are composed of tightly packed microfilaments (actin) that provide structural support and stability. Microvilli are particularly abundant in intestinal cells, enhancing nutrient uptake.
Pseudopodia
Pseudopodia are temporary, arm-like extensions of the cell membrane used by cells for movement and capturing food. They are formed by the polymerization of actin filaments and are critical for the motility of amoebas and certain immune cells. Pseudopodia are involved in processes like phagocytosis and cell migration.
Intermediate Filaments
Intermediate filaments are a diverse group of fibrous proteins that provide mechanical strength to cells and help maintain their shape. Unlike microtubules and microfilaments, they are more stable and less dynamic. Intermediate filaments are crucial for the structural integrity of tissues and are important in cell signaling and the response to mechanical stress.
Cell adhesion molecules: cadherins, integrins, selectins, immunoglobulin superfamily
Cell adhesion molecules: cadherins, integrins, selectins, immunoglobulin superfamily
Introduction to Cell Adhesion Molecules
Cell adhesion molecules are crucial for maintaining the structure and function of tissues. They facilitate the adhesion between cells and between cells and the extracellular matrix. Their roles include cell signaling and regulation of cellular functions.
Cadherins
Cadherins are a class of type-1 transmembrane proteins involved in cell-cell adhesion. They require calcium ions for their adhesive function. Cadherins are essential for embryonic development, tissue formation, and maintaining tissue integrity.
Integrins
Integrins are heterodimeric proteins that mediate cell-extracellular matrix adhesion. They play vital roles in processes such as cell migration, differentiation, and communication with the extracellular matrix. Integrins transduce signals that regulate cell behavior.
Selectins
Selectins are a family of carbohydrate-binding proteins that mediate the adhesion of leukocytes to the vascular endothelium during inflammation. They play a critical role in immune responses and are involved in the process of rolling of leukocytes along the blood vessel wall.
Immunoglobulin Superfamily
The immunoglobulin superfamily is a large group of proteins known for their role in cell adhesion, immune response, and signaling. These molecules often have immunoglobulin-like domains and are involved in various functions, including mediating cell-cell interactions in the immune system.
Conclusion
Understanding the various cell adhesion molecules and their functions is critical for comprehending cellular behavior in health and disease, including developmental biology and immunology.
Cell communication: autocrine, paracrine, endocrine, juxtacrine, signaling pathways including nitric oxide, EGFs, Hedgehog, Wnt, TGF-beta superfamily, BMP family, G-protein, cAMP, IP3, RTK, MAP kinase pathway
Cell communication
Types of Cell Communication
Signaling Pathways
Second Messengers and Pathways
Cell junctions: anchoring, gap, tight junctions
Cell junctions
Anchoring Junctions
Anchoring junctions provide mechanical stability to tissues by linking the cytoskeleton of one cell to that of another. They include desmosomes, which connect intermediate filaments between cells, and adherens junctions, which connect actin filaments. These junctions play crucial roles in maintaining the structural integrity and resilience of tissues.
Gap Junctions
Gap junctions are specialized intercellular connections that allow for the direct transfer of ions and small molecules between adjacent cells. They are formed by connexins that assemble into connexons, facilitating communication and coordination in tissues such as cardiac and smooth muscle.
Tight Junctions
Tight junctions create a barrier that regulates the passage of substances between epithelial cells. They are formed by proteins such as claudins and occludins that fuse the outer membranes of adjacent cells, preventing the leakage of materials and contributing to the maintenance of polarity in epithelial cells.
Cell membrane structure: lipid bilayer, peripheral and integral proteins, fluid mosaic model
Cell membrane structure
Lipid Bilayer
The cell membrane is primarily composed of a lipid bilayer, which consists of two layers of phospholipids. Each phospholipid has a hydrophilic (water-attracting) head and two hydrophobic (water-repelling) fatty acid tails. This arrangement creates a semi-permeable membrane, allowing selective passage of substances. The fluidity of the bilayer is influenced by temperature and the saturation of fatty acids.
Peripheral Proteins
Peripheral proteins are attached to the exterior or interior surfaces of the membrane. They do not penetrate the lipid bilayer. These proteins play roles in signaling, maintaining the cell's shape, and facilitating communication between cells. They can be easily dislodged from the membrane.
Integral Proteins
Integral proteins are embedded within the lipid bilayer. They can span the entire membrane (transmembrane proteins) or partially penetrate it. These proteins are integral to processes such as transport, acting as channels or carriers for molecules, and facilitating communication through receptor sites.
Fluid Mosaic Model
The fluid mosaic model describes the cell membrane as a dynamic structure. The term fluid refers to the flexible nature of the lipid bilayer, which allows lateral movement of lipids and proteins. Mosaic refers to the diverse composition of proteins floating in or on the lipid bilayer, contributing to various functions. This model reflects the complexity and functionality of the cell membrane based on its structural components.
Membrane transport mechanisms: uniport, symport, antiport, active transport including Na-K ATPases, F-type ATPases, ATP synthetases, ionophores, ion channels (ligand and voltage gated)
Membrane transport mechanisms
Uniport
Uniport refers to the transport of a single type of molecule across a membrane. This process is specific and typically occurs through a transporter protein that facilitates the movement down the concentration gradient.
Symport
Symport involves the simultaneous transport of two different substances in the same direction across a membrane. This mechanism is crucial in processes such as glucose transport, where glucose and Na+ ions are co-transported into cells.
Antiport
Antiport is characterized by the exchange of two substances across a membrane in opposite directions. A common example is the Na+/K+ pump, which expels sodium ions while importing potassium ions, helping maintain cellular concentration gradients.
Active Transport
Active transport is the energy-dependent movement of molecules against their concentration gradient. It requires ATP or another energy source to function.
Na-K ATPases
Na-K ATPases are vital for maintaining the electrochemical gradient across the plasma membrane by pumping sodium out and potassium into the cell. This activity is crucial for various cellular functions, including nerve impulse transmission.
F-type ATPases
F-type ATPases, also known as ATP synthases, are enzyme complexes that synthesize ATP from ADP and inorganic phosphate during cellular respiration, utilizing the proton gradient created by electron transport chains.
Ionophores
Ionophores are compounds that facilitate the transport of ions across lipid membranes. They can form channels in membranes or carry specific ions, affecting cellular ion concentrations and signaling.
Ion Channels
Ion channels are membrane proteins that allow selective ion flow across the membrane. They can be gated by ligands or voltage changes, playing critical roles in processes such as action potentials in neurons.
Ligand-gated Ion Channels
Ligand-gated ion channels open in response to the binding of a chemical messenger (ligand), allowing specific ions to flow across the membrane. Examples include neurotransmitter receptors.
Voltage-gated Ion Channels
Voltage-gated ion channels open or close in response to changes in membrane potential. They are essential for action potentials and signal propagation in excitable tissues.
Protein sorting: Golgi, endoplasmic reticulum, lysosome, signal recognition particles, chaperones, protein folding, post-translational modifications, vesicular transport, GPI anchoring, mitochondrial targeting
Protein sorting
The Golgi apparatus is crucial for post-translational modification and sorting of proteins. It consists of a series of flattened membrane-bound compartments where glycosylation occurs, and proteins are packaged into vesicles for transport.
The endoplasmic reticulum (ER) is divided into rough ER, which is involved in protein synthesis, and smooth ER, which is involved in lipid synthesis. The rough ER has ribosomes on its surface, and it plays a vital role in the initial stages of protein sorting.
Lysosomes are organelles that contain digestive enzymes. Proteins destined for lysosomes are tagged with mannose-6-phosphate in the Golgi apparatus, ensuring their delivery to these structures for degradation of macromolecules.
Signal recognition particles (SRPs) are ribonucleoprotein complexes that recognize signal sequences on nascent polypeptides. They facilitate the targeting of these proteins to the ER membrane for co-translational translocation.
Chaperones are proteins that assist in the proper folding of nascent polypeptides. They prevent misfolding and aggregation by helping to stabilize unfolded proteins until they are correctly folded.
Protein folding is crucial for the functionality of proteins. It involves the transition from a linear polypeptide to a three-dimensional structure, often facilitated by chaperones and assisted by post-translational modifications.
Post-translational modifications (PTMs) are chemical modifications of proteins after synthesis. Common PTMs include phosphorylation, glycosylation, ubiquitination, and acetylation, which affect protein function, localization, and stability.
Vesicular transport is the process by which proteins are transported in vesicles between cellular compartments. This mechanism is essential for the delivery of proteins to their correct locations, including the plasma membrane and lysosomes.
Glycosylphosphatidylinositol (GPI) anchoring is a post-translational modification that attaches proteins to the cell membrane. It consists of a GPI molecule that tethers the protein to the lipid bilayer, playing critical roles in cell signaling and membrane organization.
Mitochondrial targeting involves specific signal sequences that direct proteins to mitochondria. These signals are recognized by receptor proteins on the mitochondrial membrane, facilitating the import of necessary proteins for mitochondrial function.
Cancer biology: etiological factors, tumor types, oncogenes, tumor suppressor genes, DNA tumor viruses, tumor antigens, metastasis, angiogenesis, cancer cell morphology
Cancer biology
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Etiological factors refer to the various environmental, genetic, and lifestyle influences that contribute to cancer development. They can be classified into several categories: 1. Chemical Carcinogens - Substances like tobacco smoke, certain chemicals, and pollutants. 2. Physical Agents - Such as UV radiation and ionizing radiation. 3. Biological Agents - Including viruses (like HPV, HBV), bacteria, and parasites. 4. Genetic Predisposition - Inherited mutations that increase cancer risk, such as BRCA1 and BRCA2 genes.
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Tumors are classified as benign or malignant. 1. Benign tumors - Non-cancerous growths that do not invade surrounding tissues. 2. Malignant tumors - Cancerous growths capable of invading adjacent tissues and spreading to other parts of the body. Types of malignant tumors include Carcinomas (epithelial tissues), Sarcomas (connective tissues), Lymphomas (lymphatic system), and Leukemias (blood-forming tissues).
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Oncogenes are mutated genes that have the potential to cause cancer. They usually promote cell division or inhibit apoptosis. Examples include RAS, MYC, and ERBB2. These genes can be activated by mutations, gene amplification, or chromosomal translocation.
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Tumor suppressor genes are responsible for regulating cell growth and preventing uncontrolled cell proliferation. When these genes are mutated or lost, it can lead to cancer. Important tumor suppressor genes include TP53, RB1, and APC.
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Certain viruses can induce cancer by integrating their DNA into the host cell genome, leading to altered expression of oncogenes and tumor suppressor genes. Notable examples include Human Papillomavirus (HPV) and Epstein-Barr Virus (EBV), which are linked to cervical and nasopharyngeal cancers, respectively.
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Tumor antigens are substances produced by tumor cells that can trigger an immune response. They can be classified into tumor-specific antigens (unique to cancer cells) and tumor-associated antigens (present in normal cells but overexpressed in tumors). Examples include MAGE and CEA. Immune recognition of these antigens is crucial for immunotherapy strategies.
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Metastasis is the process where cancer cells spread from the primary tumor to distant organs. It involves several steps: local invasion, intravasation into blood vessels, survival in circulation, extravasation into new tissues, and colonization. Metastatic cancer often has a different prognosis and treatment approach than localized cancer.
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Angiogenesis is the formation of new blood vessels from existing ones and is critical for tumor growth and metastasis. Tumors secrete angiogenic factors like VEGF to promote blood vessel formation, supplying nutrients and oxygen necessary for their expansion.
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Cancer cells exhibit distinct morphological features compared to normal cells. They often have irregular shapes, larger nuclei, and increased mitotic figures. The degree of differentiation varies, with poorly differentiated cells often appearing more aggressive and less specialized.
