The Cell as a Unit of Health and.pptx

The Cell as a Unit of Health and Disease: The Genome and Cellular housekeeping ABUAD MBBS 400 LEVEL BLOCK 1 LECTURE DELIVERED BY: DR. UCHIME KASIEMOBI E. The Genome The genome is the complete set of genes or genetic material present in a cell or...

The Cell as a Unit of Health and Disease: The Genome and Cellular housekeeping ABUAD MBBS 400 LEVEL BLOCK 1 LECTURE DELIVERED BY: DR. UCHIME KASIEMOBI E. The Genome The genome is the complete set of genes or genetic material present in a cell or organism. The human genome is a complete set of nucleic acid sequences, encoded as DNA within 23 chromosomal pairs in the cell’s nuclei and in a small DNA molecule found within individual mitochondria.  THE ORGANISATION OF NUCLEAR DNA The Genome The human genome encodes approximately 20,000 protein, Protein-coding sequences account for only 1.5% of the total genome. Up to 80% of the remaining DNA comprises of non-coding functional sequences that can bind proteins or otherwise regulate gene expression.  The Genome The non-coding functional sequences include: Promoter and enhancer regions (binding sites for transcription factors. Binding sites for factors that maintain higher- order chromatin structures - Non-coding regulatory RNAs (e.g., microRNAs, and long noncoding RNAs) - Mobile genetic elements (e.g., transposons) - Special structural regions of DNA(e.g., telomeres and centromeres) The Genome Any Two individual share >99.5% of their DNA sequences Person-to person variation is encoded in 75 daltons (e.g., sugar and nucleotides) and all ions (require specialized protein transporter) Note that the Na+/K+ ATPase (affected in cell injury) on the cellular membrane helps maintain intracellular osmolarity. These transport system also help maintain intracellular pH.  Plasma membrane: Protection and Nutrient Acquisition 3. Receptor-Mediated and Fluid-Phase Uptake: Involves endocytosis which allows the import of macromolecules > 1000 daltons. It can be via: A. Caveolae-mediated endocytosis (“little caves”) B. Pinocytosis (“cellular drinking) C. Receptor-Mediated endocytosis (mainly for macromolecules like transferrin and LDL) Defect in receptor-mediated uptake or processing of LDL can be responsible for familial hypercholesterolemia.  MOVEMENT OF SMALL MOLECULES AND LARGER STRUCTURE ACROSS MEMBRANES Cytoskeleton and Cell-Cell Interaction Cell shape, polarity, intracellular trafficking, and motility depend on intracellular cytoskeleton proteins. These proteins include: Actin microfilaments Intermediate filaments: lamin A, B and C, Vimentin, Desmin, Neurofilaments, GFAP, Cytokeratins Microtubules Cytoskeleton and Cell-Cell Interaction Cell-cell interaction: cells interact and communicate via junctional complexes. These include: A. Occulding junctions (tight junctions) B. Anchoring junctions (desmosomes associated with cadherins): - spot desmosomes/macula adherens, -belt desmosomes, - hemidesmosome, - focal adhesion complexes Cytoskeleton and Cell-Cell Interaction C. Communicating junctions (gap junctions): mediate the passage of chemical or electric signals between cells. These juctions are formed by hexamers of transmembrane proteins called connexins. The permeability of gap junction is reduced by acidic pH or increased intracellular calcium Important in cell-cell communication in cardiac myocytes. CYTOSKELETAL ELEMENTS AND CELL-CELL INTERACTIONS Biosynthetic Machinery: Endoplasmic Reticulum and Golgi All cell constituents are constantly renewed and degraded Endoplasmic reticulum: -membrane proteins, lipids, molecules destined for exported are synthesized within the ER. Rough endoplasmic reticulum (RER) Smooth endoplasmic reticulum (SER) *ER Stress response/Unfolded protein response (UPR) apoptosis. ENDOPLASMIC RETICULUM ULTRASTRUCTURE/ELECTRON MICROGRAPHS OF CELLULAR ENDOMEMBRANE SYSTEM Waste disposal: Lysosomes and Proteosomes They are involved in cellular constituent degradation Lysosomes contain acid hydrolases, including proteases, nucleases, lipases, glycosidases, phosphatases, and sulfatases. Molecules for lysosomal degradatin are taken in via: - M6P-modified protein targeted to the lysosome - Pinocytosis or receptor-mediated endocytosis  - Autophagy, for senescent organelles and large, denatured protein complexes  - Phagocytosis, e.g. for micro-organism Waste disposal: Lysosomes and Proteosomes Proteosomes (“cylinder of death”), a protease complexes that degrade: - cytosolic proteins, including denatured or misfolded proteins - other macromolecules whose lifespan must be regulated (e.g. transcription factors) Many proteins destined for proteosome destruction are MITOCHONDRIA “Power-house” of the cell Contain its own DNA Involved in oxidative phosporylation Sensitive to antibacterial antibiotics Half lives of 1 to 10 days Has two separate membranes surrounding a core matrix containing most mitochondrial metabolic enzymes MITOCHONDRIA The inner membrane is folded into cristae which contains the enzymes of the respiratory chain The outer membrane contain porin proteins that form aqueous channels permeable to small (