The Cell as a Unit of Health and Disease PDF

# The Cell as a Unit of Health and Disease ## Chapter contents - The Genome - Noncoding DNA - Histone Organization - Micro-RNA and Long Noncoding RNA - Micro-RNA - Long Noncoding RNA - Gene Editing - Cellular Housekeeping - Plasma Membrane - Protectio...

# The Cell as a Unit of Health and Disease ## Chapter contents - The Genome - Noncoding DNA - Histone Organization - Micro-RNA and Long Noncoding RNA - Micro-RNA - Long Noncoding RNA - Gene Editing - Cellular Housekeeping - Plasma Membrane - Protection and Nutrient Acquisition - Membrane Transport - Cytoskeleton - Cell-Cell Interactions - Biosynthetic Machinery - Endoplasmic Reticulum and Golgi - Waste Disposal - Lysosomes and Proteasomes - Cellular Metabolism and Mitochondrial Function - Cellular Activation - Signal Transduction Pathways - Modular Signaling Proteins, Hubs, - Transcription Factors - Growth Factors and Receptors - Extracellular Matrix - Maintaining Cell Populations - Proliferation and the Cell Cycle - Stem Cells - Regenerative Medicine ## The Genome The human genome contains 3.2 billion DNA base pairs. Only about 20,000 protein-encoding genes are present which constitute just 1.5% of the genome. These genes are the blueprints that instruct the assembly of the enzymes, structural elements, and signaling molecules within the human body's 50 trillion cells. ### Noncoding DNA - Promoter and enhancer regions that provide binding sites for transcription factors. - Binding sites for factors that organize and maintain higher order chromatin structures - Noncoding regulatory RNAs: 60% of the genome is transcribed into RNA that is never translated. These transcribed RNA regulate gene expression via a variety of mechanisms. Two types are micro-RNAs (miRNAs) and long noncoding RNAs (IncRNAs) - Mobile genetic elements (e.g. transposons): These make up more than a third of the human genome. These "jumping genes" can move around the genome during evolution, resulting in variable copy number and positioning. - Special structural regions of DNA: Telomeres (chromosome ends) and centromeres (chromosome "tethers"). Centromeres contain large arrays of satellite DNA (from. 5 bp up to 5 kb). ## Cellular housekeeping **Normal cellular functioning and intracellular homeostasis depend on a series of fundamental cell housekeeping functions:** - **Protection from the environment**: Protecting the cell from the environment requires a constant supply of energy and the building blocks for macromolecule synthesis. - **Nutrient acquisition**: Most of the ATP that powers cells is generated via mitochondrial oxidative phosphorylation. - **Metabolism**: Mitochondria also serve as a source of metabolic intermediates needed for anabolic metabolism, are sites of synthesis of certain macromolecules, and contain important sensors of cell damage (e.g., apoptosis) that initiate and regulate programmed cell death. - **Communication**: In growing and dividing cells, all these organelles have to be replicated, and correctly apportioned in daughter cells following mitosis. - **Movement**: Movement of both organelles and proteins within the cell, as well as the entire cell in its environment, is accomplished by the cytoskeleton, which is comprised of filamentous actin, keratins, and microtubules. These structural proteins also maintain cellular shape and intracellular organization, which are essential to generation and maintenance of cell polarity. - **Renewal of senescent molecules**: The ER is the site for synthesis of all transmembrane proteins and lipids for the plasma membrane and cellular organelles, including the ER itself. - **Molecular catabolism**: Cells catabolize the wide variety of molecules that they endocytose, as well as their entire repertoire of their own proteins and organelles - all of which are constantly being degraded and renewed. The main sites of catabolism are: - **Proteasomes** degrade denatured or "tagged" cytosolic proteins. - **Lysosomes** are intracellular organelles containing degradative enzymes that permit the digestion of a wide range of macromolecules. - **Peroxisomes** contain catalase and other oxidative enzymes. - **Energy generation**: Each mitochondrion has two separate membranes with distinct functions; the inner membrane contains the enzymes of the respiratory chain folded into cristae. - **Intermediate metabolism**: Oxidative phosphorylation efficiently generates 36 to 38 ATP molecules per glucose molecule. - **Cell death**: Mitochondria play a fundamental role in regulating apoptosis. ## Cellular Activation **The ability of cells to adopt a particular shape, maintain polarity, organize intracellular organelles, and migrate depends on an intracellular scaffold of structural proteins that form the cytoskeleton.** - **Actin microfilaments**: are 5- to 9-nm diameter fibrils formed from the globular protein actin (G-actin). - **Intermediate filaments**: predominantly form rope-like polymers and do not usually actively reorganize like actin and microtubules. - **Microtubules**: are 25-nm-thick fibrils composed of noncovalently polymerized a- and ß-tubulin dimers organized into hollow tubes. **Cells connect and communicate with each other via junctional complexes that form mechanical links and facilitate receptor-ligand interactions:** * **Occluding junctions (tight junctions)** seal adjacent epithelial cells together to create a continuous barrier * **Anchoring junctions (adherens junctions and desmosomes)** mechanically attaches cells to other cells or the ECM. * **Communicating junctions (gap junctions)** permit the diffusion of chemical or electrical signals from one cell to another. **All cellular constituents — including structural proteins, enzymes, transcription factors, and even the phospholipid membrane — are constantly renewed in an ongoing process balancing synthesis and degradation. ** - **Rough endoplasmic reticulum (RER)**: membrane-bound ribosomes on the cytosolic face of RER translate mRNA into proteins that are extruded into the ER lumen or become integrated into the ER membrane. - **Golgi apparatus**: From the RER proteins and lipids destined for other organelles or extracellular export are shuttled into the Golgi apparatus. - **Smooth endoplasmic reticulum (SER)**: The SER may, however, be particularly conspicuous in cells that synthesize steroid hormones or that catabolize lipid-soluble molecules. ## Extracellular matrix The ECM is a protein network that constitutes a significant proportion of any tissue. Cell interactions with the ECM are critical for development, healing, and maintenance of normal tissue architecture. - **Interstitial matrix** occupies the spaces between stromal cells within connective tissue and between parenchymal epithelium and the underlying supportive vascular and smooth muscle structures in some organs. - **Basement membrane** acts as a boundary between epithelium and underlying connective tissue. **Components of the extracellular matrix** * Fibrous structural proteins * Water-hydrated gels * Adhesive glycoproteins ## Maintaining cell populations **Cell proliferation is fundamental to organism development. ** - **Proliferation and the Cell Cycle**: The sequence of events that results in cell proliferation is called the cell cycle; it consists of G₁ (gap 1), S (DNA synthesis), G₂ (gap 2), and M (mitotic) phases. - **Stem Cells**: Stem cells have the dual property of being able to self-renew and to give rise to differentiated cells. They are responsible for maintaining cell populations within the tissues where they reside. - **Regenerative Medicine**: The burgeoning field of regenerative medicine has been made possible by the ability to identify, isolate, expand, and transplant stem cells.