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Human Structure and Function (MEDI101) Fundamentals of Cell Biology Dr. Haissam A. Saleh Associate Professor of Biomedical Sciences Department of Biomedical Sciences College of Health Sciences Qatar University Learning Objectives At the end of the lecture, students will learn about the following con...

Human Structure and Function (MEDI101) Fundamentals of Cell Biology Dr. Haissam A. Saleh Associate Professor of Biomedical Sciences Department of Biomedical Sciences College of Health Sciences Qatar University Learning Objectives At the end of the lecture, students will learn about the following concepts:  Cell Structure and Function Types of Membrane Transport Cell Organelles Gene Expression and Protein Synthesis Cell Division - Mitosis and Meiosis PART I  Cell Structure and Function  Types of Membrane Transport The Cell Theory 1. A cell is the basic unit of life (nothing smaller than a cell is considered to be alive) 2. All living things are made up of cells 3. New cells arise from pre-existing cells Cell Diversity and Function Blood Cells Cells have various functions in the organism’s body Nerve Cells The function is determined by their shape and by the specific subcellular structures A cell’s structure and function are related to one Epithelial Cells (Skin) another  Structure-Function Relationship Sperm Cells Structure - Function Relationship C) Contractile cells Cellular Compartments Cellular compartments means that different parts of a cell are like separate rooms, each designed for a specific task, so the cell can work efficiently. The major cellular compartment are: 1. 2. 3. 4. Plasma membrane Nucleus Cytoplasm Endoplasmic Reticulum Plasma Membrane All human cells are surrounded by a plasma membrane The plasma membrane marks the boundary between the outside and the inside of the cell The integrity and function of the plasma membrane are necessary to the cell’s life Plasma Membrane Features 1. It is a phospholipid bilayer (made of 2 layers) 2. It is embedded with proteins 3. It contains cholesterol for support 4. It contains carbohydrates (sugars) attached to proteins and lipids  The polar “heads” of phospholipid molecules are hydrophilic and are attracted to water on the inner and outer surfaces of the membrane  Their nonpolar “tails” of phospholipid molecules are hydrophobic, avoid water and line up in the central (interior) part of the membrane Types of Plasma Membrane Proteins Plasma Membrane Permeability  The plasma membrane is a selectively permeable barrier; allows some substances to pass through it while excluding others  The ability of molecules to pass through a plasma membrane depends on the 1) charge/polarity, and 2) size of the molecules  In general, plasma membrane is permeable to small/non-charged/non-polar molecules, and impermeable to large/polar/charged molecules  However, essential cell proteins and large molecules are brought into the cell, and other substances, proteins, and wastes are allowed to pass out of it Test Your Knowledge Give examples of: 1- Small non-charged and non-polar molecules?...... 2- Small polar molecules?.... 3- Large polar molecules?.... 4- What about ions?.................. How Do Molecules Move Across Plasma Membranes? 1. Passive Processes (Diffusion) 2. Active Processes Simple Diffusion Facilitated Diffusion (carrier, channel) Osmosis (water channels) Active Transport Endocytosis Exocytosis  Primary  Secondary Passive Transport Processes Across Plasma Membrane Steroids, Lipids Glucose, Amino acids Cl-, Na+, Ca2+ H2O Facilitated Diffusion- Glucose Transporters  Glucose is transported into the cells by facilitated transport down its concentration gradient with the help of a protein carrier called transporter   No cellular energy is required  Some form of Diabetes may occur when a number of glucose transporters are altered within the cells Osmosis (Diffusion of Water) Active Transport Processes Across Plasma Membrane Primary Active Transport- Na+/K+ Pump Primary active transport directly uses ATP energy to transport a solute against its concentration gradient establishing an electrochemical gradient across a membrane Secondary Active TransportSecondary active transport uses a preexisting gradient to drive the active transport. It is often coupled to primary active transport and relies on the energy stored in an electrochemical gradient created by primary active transport to move a molecule against its concentration gradient. (Non Specific) (Highly Specific) Receptor-Mediated Endocytosis: Mechanisms of SARS-CoV-2 Entry into Cells Coronavirus Spike Proteins ACE2 Cell Receptors PART II  Cell Organelles Cell Organelles The Cytoplasm The fluid filling the inside of a cell containing : Organelles (ribosomes, mitochondria, Golgi apparatus, Lysosomes, etc.,) Solutes and nutrients (ions, vitamins, nucleotides, amino acids, proteins, enzymes, minerals, etc.,) Inclusion bodies such as:  Lipid droplets common in fat cells  Glycogen granules abundant in liver and muscle cells  Pigments such as melanin in skin and hair cells  Mucus in goblet cells Liver Cell Fat Cell The Nucleus  The most prominent structure in the cell is the nucleus  It contains the DNA and is surrounded by the nuclear envelope, composed of inner and outer membranes and encloses a jelly-like fluid called nucleoplasm  The nuclear envelope has numerous openings called pores, each of which is a transport channel lined with a nuclear pore complex  Chromosomes are most easily visualized during mitosis, whereas during interphase they are dispersed as chromatin and difficult to visualize  Nucleoli (singular: nucleolus) are present in the nucleus: site of rRNA synthesis and assembly of ribosomes subunits Endoplasmic Reticulum and Ribosomes  The Endoplasmic Reticulum (ER) is a network of membranes that is continuous with the other membranes in the cell facilitating the exchange of materials and the coordination of cellular processes. ER can be rough or smooth in appearance.  Rough ER (RER) is studded with ribosomes on the cytoplasmic side of the membrane and is involved in: Protein synthesis and modification.  Free-floating ribosomes are not associated with the ER and synthesize proteins for immediate use by the cell.  Smooth ER (SER) has no role in protein synthesis and is involved in: Synthesis of lipids and steroids such as cholesterol and its derivatives (estrogens, testosterone)  Detoxification of harmful substances  Storage and release of Ca2+ ions that triggers muscle contraction Carbohydrates metabolism (glucose) Lysosomes  Lysosomes are single-membrane organelles that bud from the Golgi complex. They store hydrolases, enzymes that digest various biological molecules.  Functions:  Fuses with and digests substances that enter a cell via endocytosis (e.g., phagocytosis)  Carry out autophagy, the digestion of worn-out organelles  Execute apoptosis, the digestion of an entire cell Proteasomes  Proteasomes are barrel-shaped cellular protein complexes that contains proteases which degrade unneeded, damaged, or faulty cytoplasmic proteins by cutting them into small peptides and amino acids  By degrading and recycling proteins, they play a crucial role in maintaining cellular health and regulating various cellular processes Protein is degraded to small peptides and amino acids and are recycled back to the cytosol Protein destined for degradation is injected into the core proteasome Golgi Apparatus  The products of the ER are transported to the Golgi apparatus by vesicles for further processing. The Golgi apparatus, closely related to the ER in proximity and function, consists of a stack of flattened vesicles known as cisternae.  The Golgi sorts and packages modified proteins, lipids, and other macromolecules into vesicles for transport to various destinations inside or outside the cell. Cisternae Mitochondria  Mitochondria are referred to as the “powerhouses” of the cell  Mitochondria are surrounded by a double-membrane, consisting of outer and inner mitochondrial membranes  The inner membrane forms numerous folds (cristae), which extend into the interior (or matrix) of the organelle.  Functions: 1. Generate ATP through reactions of aerobic cellular respiration. 2. Play an important early role in apoptosis. Cytoskeleton A series of proteins that maintain cell shape, as well as anchors and/or moves organelles in the cell. Made of 3 types of fibers: 1. Microfilaments (Actin filaments) 2. Intermediate filaments 3. Microtubules Microfilaments  Also called Actin filaments  Diameter size: 8 nm  Primarily composed of polymers of Actin  Function includes: Cell contractility Cytokinesis (division of cytoplasm) Amoeboid movement (pseudopods) Cell motility Changes in cell shape Mechanical stability Green = Microtubules Red = Microfilaments Intermediate Filaments  Diameter size 8- 12 nm  Composed of many protein types such as Keratin and Vimentin  Function includes: Tension bearing Maintenance of cell shape Anchoring of the nucleus and other organelles No role in cell movement Uterus Endometrial Cell Vimentin Intermediate Filament Network Nucleus Microtubules Micrograph showing condensed chromosomes (blue), kinetochores (pink), microtubules (green) during metaphase of mitosis  The largest of the cytoskeletal (Diameter size 25 nm)  Composed mainly of the protein Tubulin  Microtubules are dynamic structures that undergo continual assembly and disassembly within the cell  Function includes: Cell motility Cell shape and structure Intracellular transport of organelles (secretory vesicles) Movement of cilia and flagella Spindle apparatus assembly during cell division Centrosomes  The centrosome is a cellular structure that plays an important role in cell division  It is usually located within the cytoplasm close to the nucleus and consists of two centrioles — oriented at right angles to each other  Centrioles are made up of nine circularly arranged triplet of microtubules  Before cell division, the centrosome duplicates and then, as division begins, the two centrosomes move to opposite ends of the cell 9 x 3 = 27 microtubules Cilia and Flagella  Cytoplasmic outgrowths extending from the plasma membrane  Cilia: Short and many  Flagella: Long and single  Cilia are about 20 shorter than flagella  Both are used for movement Cilia move fluids along a cell’s surface Flagellum moves an entire cell  Cilia are found in the lining of the trachea (windpipe), where they sweep mucus and dirt out of the lungs and in the lining of the fallopian tube (oviduct), where they convey released ova to they uterine cavity Specialized Cell Junctions Cells interact and communicate with each another by forming junctions that provide mechanical links and enable surface receptors to recognize ligands on other cells. The main types are: 1. Tight (impermeable) junctions– Prevent substances from penetration through the cellular layer (predominant in urinary system, stomach, small intestine cells) 2. Desmosomes (anchoring) junction– Prevent cells subjected to mechanical stress from being pulled apart (predominant in epidermis and cardiac cells) 3. Gap (communicating) junctions - Facilitate direct communication between cells and passage of ions and small molecules (predominant in neurons and different types of muscle cells including cardiac cells) PART III  Gene Expression and Protein Synthesis Chromatin and Chromosomes  Chromatin is a complex network made of long strands of DNA wrapped around proteins known as histones  These histones serve as beads around which the DNA is wrapped, forming bead-like structures called nucleosomes  In non-dividing cells, chromatin exists in a decondensed state and is scattered throughout the nucleus  When cells undergo division, chromatin threads condense to form chromosomes DNA Nucleic Acids  Nucleic acids are responsible for the storage, expression, and transmission of genetic information  Two classes:  Deoxyribonucleic Acid (DNA)  Stores genetic information  Ribonucleic Acid (RNA)  Transfer of genetic information from DNA to form a protein Deoxyribonucleic Acid (DNA)  DNA is a polymer composed of two polynucleotide strands that coil around each other to form a double helix structure DNA nucleotide = Nitrogenous Base + Deoxyribose Sugar + Phosphate Group  Nitrogenous bases: 1. Pyrimidines- Thymine (T) & Cytosine (C) 2. Purines- Adenine (A) & Guanine (G)  Base pairing rules:  A pairs with T (via Hydrogen bond)  C pairs with G (via Hydrogen bond) Ribonucleic Acid (RNA)  RNA is a polymer composed of one strand of nucleotides  RNA nucleotide = Nitrogenous Base + Ribose Sugar + Phosphate Group  Nitrogenous bases: 1. Pyrimidines- Uracil (U) & Cytosine (C) 2. Purines- Adenine (A) & Guanine (G)  Base pairing rules:  A pairs with U (via Hydrogen bond)  C pairs with G (via Hydrogen bond)  There are 3 types of RNA: 1. Messenger RNA (mRNA) directs the synthesis of a protein 2. Ribosomal RNA (rRNA) play a crucial role in protein synthesis and is a fundamental component of ribosomes 3. Transfer RNA (tRNA) carries specific amino acids to the ribosome during protein synthesis, ensuring the accurate assembly of proteins based on the genetic code in mRNA DNA vs RNA DNA RNA Deoxyribonucleic acid Ribonucleic acid Deoxyribose Ribose Thymine (T) Uracil (U) Adenine (A), guanine (G), cytosine (C) used in both Double strand Single strand 1 type 3 types Gene Expression and Protein Synthesis DNA Transcription  The genetic information is contained in the sequence of base pairs in DNA. During protein synthesis, codons, which are sequences of 3 nucleotides in mRNA, code for the incorporation of specific amino acids or signal the termination of protein synthesis (stop signals)  DNA (template strand) serves as a template for copying the information into a complementary sequence of RNA by RNA polymerase enzyme. The mRNA is a copy of the DNA coding strand ( U replaces T). Template strand Coding strand During transcription, bases pair in a complementary manner where U replaces T. DNA Transcription: Where to Start and End ?  Promoter- segment of DNA where transcription begins. It serves as recognition sites for RNA polymerase and other regulatory proteins.  Terminator is the segment of DNA where transcription ends. Protein Synthesis  Proteins are large, complex polymers composed of amino acid molecules  These amino acids are covalently bonded together via peptide bonds to form a linear chain Start Codon Codon & Anticodon  A codon consists of 3 adjacent bases in an mRNA molecule that codes for a specific amino acid.  Each tRNA carries a specific amino acid at one end.  At the other end, each tRNA has 3 nucleotides forming an anticodon, which is complementary to the codon in the mRNA. mRNA Genetic code – sequence of bases in an mRNA molecule Specifies the sequence of amino acids within a polypeptide Read in groups of 3 bases or codons Most codons specify a particular amino acid, or Start and Stop codons More than one codon can specify the same amino acid. Mechanisms of Translation  Amino acids are joined together to make a Polypeptide Stages of Translation E site E site A site E site E site A site E site A site Illustrative Summary of Gene Expression PART IV Cell Division- Mitosis and Meiosis Cell Cycle  A cell cycle is a series of events that occurs in a cell as it grows and divides. Typically the cell cycle consists of two major phases: 1. Interphase (non-dividing phase) 2. Mitosis (dividing phase)  Interphase G1 phase– first gap S phase– synthesis of DNA G2 phase– second gap  Mitosis G0 is an alternative pathway for cells that either postpone division or never divide again, as seen in certain cells like neurons and cardiomyocytes. G0 represents a non-dividing phase. Somatic Cell division (Mitosis)  Somatic cell division is made of two events: 1- Mitosis: division of the nucleus 2- Cytokinesis: division of the cytoplasm  Each daughter cell ends up with exactly the same genetic information as the original mother cell  Somatic cells are diploid cells (2N) which contain 23 pairs of chromosomes (46 chromosomes) consisting of 22 pairs autosomes chromosomes + 1 pair sex chromosomes (XX or XY)  One member of each pair is inherited from each parent  Before cell division, each pair of chromosomes duplicates into two sister chromatids held together by a centromere Karyotype  Karyotype is a photographic representation of an individual complete set of chromosomes (often performed during metaphase where chromosomes are duplicated and most condensed and visible)  A diploid cell has two complete sets of chromosomes (inherited from each parent)  2N = 46 chromosomes  22+ XX = Female  22+ XY = Male Phases of Mitosis Mitosis consists of 5 phases: 1- Prophase 2- Prometaphase 3- Metaphase 4- Anaphase 5- Telophase Mitosis Mitosis Meiosis and Sexual Reproduction  Sexual reproduction requires a fertilization event in which two haploid gametes (containing a single set of chromosomes) unite to create a diploid cell called a zygote  Meiosis (making smaller) is the process by which haploid cells are produced from a diploid cell  The chromosomes must be sorted and distributed in a way that reduces the chromosome number to the half  Two rounds of divisions are necessary: Meiosis I and Meiosis II  Meiosis I consists of 5 phases: Prophase I, Prometaphase I, Metaphase I, Anaphase I, and Telophase I  Meiosis II consists of 5 phases: Prophase II, Prometaphase II, Metaphase II, Anaphase II, and Telophase II Cytokinesis Cytokinesis Features of Meiosis  Like mitosis, meiosis begins after a cell has progressed through the G1, S, and G2 phases of the cell cycle  Two key differences in the beginning of meiosis (prophase): 1. Formation of Bivalent/Tetrad- Homologous pairs of sister chromatids associate with each other, lying side by side to form a bivalent or tetrad, a process called synapsis 2. Crossing Over- Physical exchange between chromosome pieces of the crossing bivalent:  May increase the genetic variation of a species  Chiasma – arms of the chromosomes tend to separate but remain adhered at a crossover site Meiosis I Mitosis vs Meiosis Mitosis produces 2 diploid daughter cells that are genetically identical Meiosis produces 4 haploid daughter cells that are genetically different Meiosis Underlies Spermatogenesis and Oogenesis Aging and Cell Death  Cell aging and death (cellular senescence and apoptosis), are essential processes in the life cycle of organisms. Over time, cells undergo aging due to a combination of factors, including: 1. Shortening of telomeres – protective caps on the ends of chromosomes 2. Accumulation of cellular damage- caused by factors like free radicals and glycation (glycation is a chemical process in which sugar molecules attach to proteins, lipids, or nucleic acids unnaturally) To maintain the health of the organism, damaged or malfunctioning cells are often eliminated through apoptosis, a programmed cell death mechanism  The fine balance between cell aging and apoptosis plays a pivotal role in the overall health and aging of an organism Thank You for Your Attention

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