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Chapter 3 The Cellular Level of Organization INTRODUCTION • A cell is the basic, living, structural, and functional unit of the body. • Cytology is the study of cell structure • Cell physiology is the study of cell function. PARTS of a CELL • The cell can be divided into three principal parts for ease of study. • Plasma (cell) membrane • Cytoplasm – Cytosol – Organelles (except for the nucleus) • Nucleus THE PLASMA MEMBRANE • The plasma membrane is a flexible, sturdy barrier that surrounds and contains the cytoplasm of the cell. • Fluid mosaic model (Figure 3.2). – The membrane consists of proteins in a sea of lipids. Lipid Bilayer of the Cell Membrane • Two back-to-back layers of 3 types of lipid molecules • Cholesterol and glycolipids scattered among a double row of phospholipid molecules Phospholipids • Comprises 75% of cell membrane • Phospholipid bilayer = • Each molecule is amphipathic – polar parts (heads) are hydrophilic and face on both surfaces a watery environment – nonpolar parts (tails) are hydrophobic and line up next to each other in the interior Cholesterol within the Cell Membrane • Comprises 20% of cell membrane lipids • Interspersed among the other lipids in both layers Glycolipids within the Cell Membrane • Comprises 5% of the lipids of the cell membrane Membrane Proteins Integral versus Peripheral Proteins Functions of Membrane Proteins • Membrane proteins vary in different cells and functions (Figure 3.3) • The different proteins help to determine many of the functions of the plasma membrane. Functions of Membrane Proteins • Formation of Channel • Transporter Proteins • Receptor Proteins Functions of Membrane Proteins • Cell Identity Marker • Linker • Act as Enzyme Membrane Permeability • Plasma membranes are selectively permeable. • The lipid bilayer portion of the membrane is permeable to but impermeable to • Transmembrane proteins • Macromolecules are unable to pass through the plasma membrane. Gradients Across Membrane • Concentration gradient • Electrical gradient TRANSPORT ACROSS THE PLASMA MEMBRANE • Three types of passive processes –1 –2 –3 • Active transport requires cellular • Materials can also enter or leave the cell through vesicle transport. Principles of Diffusion • Diffusion (Figure 3.6) • Diffusion rate across plasma membranes is influenced by several factors: Diffusion • Crystal of dye placed in a cylinder of water • Net diffusion from the higher dye concentration to the region of lower dye • Equilibrium has been reached in the far right cylinder Diffusion Through the Lipid Bilayer • Nonpolar, hydrophobic molecules such as respiratory gases, some lipids, small alcohols, and ammonia can diffuse across the lipid bilayer. • It is important for gas exchange, absorption of some nutrients, and excretion of some wastes. Diffusion Through Membrane Channels • Most membrane channels are ion channels, allowing passage of small, inorganic ions which are hydrophilic. • Ion channels are selective and specific and may be gated or open all the time (Figure 3.6). Osmosis • Osmosis is the net movement of a solvent through a selectively permeable membrane, or in living systems, the movement of water (the solute) from an area of higher concentration to an area of lower concentration across the membrane (Figure 3.7). Tonicity • In an isotonic solution, red blood cells (Figure 3.8a). • In a hypotonic solution, red blood cells (Figure 3.8b). • In a hypertonic solution, red blood cells (Figure 3.8c). Facilitated Diffusion • In facilitated diffusion, a solute binds to a specific transporter on one side of the membrane and is released on the other side after the transporter undergoes a conformational change. Examples: (Figure 3.6a). • Rate of movement depends upon – steepness of concentration gradient – number of transporter proteins (transport maximum) Facilitated Diffusion of Glucose • Glucose binds to transport protein • Transport protein changes shape • Glucose moves across cell membrane (but only down the concentration gradient) • Kinase enzyme reduces glucose concentration inside the cell by transforming glucose into glucose-6-phosphate • Transporter proteins always bring glucose into cell Active Transport • Active transport • In primary active transport, energy derived from ATP changes the shape of a transporter protein, which pumps a substance across a plasma membrane against its concentration gradient. Primary Active Transport • The most prevalent primary active transport mechanism is the sodium ion/potassium ion pump (Figure 3.10). – requires 40% of cellular ATP – all cells have 1000s of them – maintains low concentration of Na+ and a high concentration of K+ in the cytosol – operates continuously Secondary Active Transport • In secondary active transport, the energy stored in the form of a sodium or hydrogen ion concentration gradient is used to drive other substances against their own concentration gradients. • Plasma membranes contain several antiporters and symporters powered by the sodium ion gradient (Figure 3.11a). One in & one out. vs. Both going in Digitalis • Digitalis slows the sodium ion-calcium ion antiporters, allowing more calcium to stay inside heart muscle cells, which increases the force of their contraction and thus strengthens the heartbeat. Transport in Vesicles • A vesicle is a small membranous sac formed by budding off from an existing membrane. – endocytosis – exocytosis Overview: Vesicular Transport of Particles • Endocytosis = bringing something into cell – phagocytosis = cell eating by macrophages & WBCs • particle binds to receptor protein • whole bacteria or viruses are engulfed & later digested – pinocytosis = cell drinking • no receptor proteins • Exocytosis = release something from cell • Vesicles form inside cell, fuse to cell membrane • Release their contents – digestive enzymes, hormones, neurotransmitters or waste products Endocytosis • In endocytosis, materials move into a cell in a vesicle formed from the plasma membrane. • Receptor-mediated endocytosis is the selective uptake of large molecules and particles by cells (Figure 3.12). Exocytosis • In exocytosis, membrane-enclosed structures called secretory vesicles that form inside the cell fuse with the plasma membrane and release their contents into the extracellular fluid. CYTOPLASM • Cytosol is composed mostly of water, plus proteins, carbohydrates, lipids, and inorganic substances. • Cytosol is the medium in which many metabolic reactions occur. Organelles • Organelles are specialized structures that have characteristic shapes and perform specific functions in cellular growth, maintenance, and reproduction. Cytoskeleton • Network of protein filaments throughout the cytosol • Functions: Microfilaments (Figure 3.15a) Intermediate Filaments (Figure 3.15b) Microtubules (Figure 3.15c) Centrosomes (Figure 3.16a – 3.16c) Cilia and Flagella • Cilia (Figure. 3.17a – 3.17b). • Flagella (Figure 3.17c). Cilia and Flagella • Structure – pairs of microtubules (9+2 array) • Differences – cilia • short and multiple – flagella • longer and single Ribosomes • Composed of Ribosomal RNA & protein • Free ribosomes – synthesize proteins found inside the cell • Membrane-bound ribosomes – synthesize proteins needed for plasma membrane or for export Ribosomal Subunits • Large + small subunits – made in the nucleolus – assembled in the cytoplasm Endoplasmic Reticulum • (Figure 3.19). Endoplasmic Reticulum • Rough ER • Smooth ER • The ER transports substances, stores newly synthesized molecules, synthesizes and packages molecules, detoxifies chemicals, and releases calcium ions involved in muscle contraction. • (Figure 3.20) Golgi Complex Golgi Complex • The principal function of the Golgi complex is to process, sort, and deliver proteins and lipids to the plasma membrane, lysosomes, and secretory vesicles (Figure 3.21). Lysosomes • membrane-enclosed vesicles that contain powerful digestive enzymes (Figure 3.22). • Functions – digest foreign substances Tay-Sachs Disorder • Affects children of eastern European-Ashkenazi descent – seizures, muscle rigidity, blind, demented and dead before the age of 5 • Genetic disorder caused by absence of single lysosomal enzyme – enzyme normally breaks down glycolipid commonly found in nerve cells – as glycolipid accumulates, nerve cells lose functionality – chromosome testing now available Peroxisomes • Peroxisomes are similar in structure to lysosomes, but are smaller. • They contain enzymes (e.g., catalase) that use molecular oxygen to oxidize various organic substances. Mitochondria • The mitochondrion is bound by a double membrane. • The outer membrane is smooth with the inner membrane arranged in folds called cristae (Figure 3.23). – surface area for chemical reactions of cellular respiration – central cavity known as matrix Mitochondria • Mitochondria are the site of ATP production in the cell. • Mitochondria self-replicate using their own DNA. – increases with need for ATP – circular DNA with 37 genes • Mitochondrial DNA (genes) are usually inherited only from the mother. NUCLEUS • The nucleus is usually the most prominent feature of a cell (Figure 3.25). NUCLEUS • Most body cells have a single nucleus. • The parts of the nucleus include the nuclear envelope which is perforated by channels called nuclear pores, nucleoli, and genetic material (DNA), • Within the nucleus are the cell’s hereditary units, called genes, which are arranged in single file along chromosomes. Function of the Nucleus • 46 human DNA molecules or chromosomes – genes found on chromosomes – gene is directions for a specific protein • Non-dividing cells contain nuclear chromatin – loosely packed DNA • Dividing cells contain chromosomes – tightly packed DNA – it doubled (copied itself) before condensing Chromosomes • Each chromosome is a long molecule of DNA that is coiled together with several proteins (Figure 3.25). PROTEIN SYNTHESIS • The instructions for protein synthesis is found in the DNA in the nucleus. • Protein synthesis involves transcription and translation (Figure 3.26). Transcription • Transcription • (Figure 3.27a). Transcription • DNA sense strand is template for the creation of messenger RNA strand • Transcription begins at promoter sequence where RNA polymerase attaches • When RNA polymerase reaches the terminator sequence it detaches and transcription stops • Pre-mRNA contains intron region that are cut out by enzymes • Exon regions of mRNA will code for segments of the protein Translation • Translation • (Figure 3.28). Translation – sequence of nucleotides on mRNA is “read” by rRNA to construct a protein (with its specific sequence of amino acid) • 3 nucleotide sequences on mRNA are called codons – specific tRNA molecule carry specific amino acids – anticodons on tRNA are matched to specific codons on mRNA so proper amino acids can be strung together to create a protein molecule The sequence of translation • Messenger RNA associates with ribosomes, which consist of tRNA and proteins. The sequence of translation • Specific amino acids attach to molecules of tRNA. Another portion of the tRNA has a triplet of nitrogenous bases called an anticodon, a codon is a segment of three bases of mRNA. The sequence of translation • Transfer RNA delivers a specific amino acid to the codon; the ribosome moves along an mRNA strand as amino acids are joined to form a growing polypeptide. CELL DIVISION • Cell division is the process by which cells reproduce themselves. It consists of nuclear division (mitosis and meiosis) and cytoplasmic division (cytokinesis). The Cell Cycle in Somatic Cells • The cell cycle is an orderly sequence of events by which a cell duplicates its contents and divides in two. • It consists of interphase and the mitotic phase (Figure 3.30). Chromosome number • Human somatic cells contain 46 chromosomes or 23 pairs of chromosomes • The two chromosomes that make up a chromosome pair are called homologous chromosomes or homologs. • A cell with a full set of chromosomes is called a diploid cell (2N). • A cell with only one chromosome from each pair is termed haploid (N). Interphase Stage of Cell Cycle • During interphase the cell carries on every life process except division. (Figure 3.30). • Doubling of DNA • Phases of interphase stage -- G1, S, and G2 – G1 = cytoplasmic increase – S = replication of chromosomes – G2 = cytoplasmic growth Replication of Chromosomes • Doubling of genetic material during interphase. (S phase) • DNA molecules unzip • Mirror copy is formed along each old strand. • Nitrogenous bases pick up complementary base • 2 complete identical DNA molecules formed Interphase • A cell in interphase shows a distinct nucleus and the absence of chromosomes (Figure 3.32a). Mitotic Phase The mitotic phase consists of mitosis (or nuclear division) and cytokinesis (or cytoplasmic division). • Mitosis is the distribution of two sets of chromosomes, one set into each of two separate nuclei. • Stages of mitosis are – Prophase – Metaphase – Anaphase – Telophase Prophase • Chromatin condenses into visible chromosomes – pair of identical chromatids held together by a centromere • Nucleolus & nuclear envelope disappear • Each centrosome moves to opposite ends of cell – forms a mitotic spindle – spindle is responsible for the separation of chromatids to each new daughter cell Metaphase • During metaphase, the centromeres line up at the exact center of the mitotic spindle (Figure 3.32c). Anaphase • Anaphase is characterized by the splitting and separation of centromeres and the movement of the two sister chromatids of each pair toward opposite poles of the cell (Figure 3.32d). Anaphase • Sister chromatids move toward opposite poles of cell – now called daughter chromosomes – movement is due to shortening of microtubules • Chromosomes appear V-shaped as they are dragged towards the poles of the cell – pull is at centromere region Telophase • Telophase begins as soon as chromatid movement stops; the identical sets of chromosomes at opposite poles of the cell uncoil and revert to their threadlike chromatin form, microtubules disappear or change form, a new nuclear envelope forms, new nucleoli appear, and the new mitotic spindle eventually breaks up (Figure 3.32 e). Cytoplasmic Division: Cytokinesis • Cytokinesis is the division of a parent cell’s cytoplasm and organelles. The process begins in late anaphase or early telophase with the formation of a cleavage furrow (Figure 3.32e). Cytoplasmic Division: Cytokinesis • When cytokinesis is complete, interphase begins again (Figure 3.32f). Cell Death • Cell death, a process called apoptosis, is triggered either from outside the cell or from inside the cell due to a “cell-suicide” gene. • Necrosis is a pathological cell death due to injury. Reproductive Cell Division • Meiosis results in the production of haploid cells that contain only 23 chromosomes. • Meiosis occurs in two successive stages: meiosis I and meiosis II. Meiosis I • Meiosis I consists of four phases: prophase I, metaphase I, anaphase I, and telophase I (Figure3.33a). Prophase I • During prophase I, the chromosomes become arranged in homologous pairs through a process called synapsis (Figure 3.33b). The resulting four chromatids form a structure called a tetrad. The tetrads may exchange genetic material between non-sister chromatids through a process known as crossing over. Metaphase I • During metaphase I, the homologous pairs of chromosomes line up along the metaphase plate of the cell, with the homologous chromosomes side by side (Figure 3.33a). Anaphase I • During anaphase I, the members of each homologous pair separate, with one member of each pair moving to an opposite pole of the cell. • The net effect of meiosis I is that each resulting cell contains only one member of each pair of homologous chromosomes. It is now haploid in number Meiosis II • Meiosis II consists of prophase II, metaphase II, anaphase II, and telophase II (Figure3.33d). • These phases are similar to those in mitosis, but result in four haploid cells. Review • Figure 3.34 compares the processes of mitosis and meiosis