Cell unit

• The human genome contains ~3.2 billion DNA base pairs
• The two main components of the human genome

  • Protein-coding DNA
  • Noncoding DNA
• Protein-coding DNA


  Comprises about 1.5% of the genome, encoding ~20,000 genes that function as enzymes, structural components, and signaling molecules
• Noncoding DNA


  Comprises about 98.5% of the genome, consisting of long stretches of DNA with unclear function, also known as the "dark matter" of the genome
• Five major classes of functional noncoding sequences in the human genome

  • Promoter and enhancer regions
  • Other binding sites
  • Noncoding regulatory RNAs
  • Mobile genetic elements
  • Special structural regions
• Most of the genetic variations associated with diseases are located in non-protein-coding regions of the genome
• The two most common forms of DNA variations

  • Single-nucleotide polymorphisms (SNPs)
  • Copy number variations (CNVs)
• Single-nucleotide polymorphisms (SNPs)


  Variants at single nucleotide positions, almost always biallelic
• Copy number variations (CNVs)

  Variants consisting of large contiguous stretches of DNA, may be biallelic or multiallelic, may be duplicated or deleted in a subset of a population, include complex rearrangements of genetic material
• Genetic variations and alterations cannot by themselves explain the diversity of phenotypes in the population
• Epigenetics


  Heritable changes in gene expression that are not caused by alterations in DNA sequence, factors "above genetics" that lead to cell type-specific differences in gene transcription and translation
• Epigenetic factors


  • Histones
  • Histone-modifying factors
• Chromatin organization


  1. Naked DNA

  2. Nucleosomes

  3. Chromatin

  4. Chromatids

  5. Chromosomes
• Histones


  • Highly conserved low molecular weight proteins that serve as the central core structure of nucleosomes
  • Regulated by a host of nuclear proteins and chemical modification
• Histone modifications


  • Methylation
  • Acetylation
  • Phosphorylation
  • DNA methylation
  • Chromatin organizing factors
• Micro-RNA (miRNA)


  Small interfering RNAs that modulate the translation of target mRNAs into their corresponding proteins (posttranscriptional silencing)
• Long Noncoding RNA


  Modulate gene expression in many different ways, such as facilitating transcription factor binding, binding transcription factors, directing histone and DNA modification, and acting as scaffolding
• Cellular housekeeping functions


  • Protection from the environment
  • Nutrient acquisition
  • Communication
  • Movement
  • Renewal of senescent molecules
  • Molecular catabolism
  • Energy generation
• Plasma membrane


  • Consists of fluid bilayers of amphipathic phospholipids, cholesterol, and associated proteins
  • Laterally fluid, with various constituents able to diffuse randomly
  • Contains lipid rafts, distinct lipid domains where inserted membrane proteins and other membrane components tend to accumulate
• Membrane proteins and glycoproteins

  • Integral or transmembrane proteins
  • Synthesized in cytosol and posttranslationally attached to prenyl groups of fatty acids
  • Inserted through GPI anchors
  • Peripheral membrane proteins
• Laterally fluid


  Various constituents can diffuse randomly
• Lipid rafts


  Distinct lipid domains where inserted membrane proteins and other membrane components tend to accumulate
• Lipid rafts


  • Important in cell-cell and cell-matrix interactions, intercellular signaling, and secretory and endocytic pathways
• Membrane proteins and glycoproteins involved in

  • Ion and metabolite transport
  • Fluid-phase and receptor-mediated uptake of macromolecules
  • Cell-ligand, cell-matrix, and cell-cell interactions
• General arrangements of membrane proteins in the membrane

  • Integral or transmembrane proteins
  • Synthesized in cytosol then posttranslationally attached to prenyl groups of fatty acids inserted in the cytosolic side of the membrane
  • Inserted through GPI anchors
  • Peripheral membrane proteins: noncovalent association with integral proteins
• How membrane proteins aggregate

  1. May be under the control of chaperone molecules in the RER

  2. May be via lateral diffusion in the plasma membrane followed by complex formation in situ
• Carbohydrates in the membrane are often studded as complex oligosaccharides on glycoproteins and glycolipids, and some are polysaccharide chains attached to internal membrane proteoglycans
• Modes of transport across the plasma membrane

  • Passive diffusion
  • Endocytosis
  • Caveolae-mediated endocytosis
  • Receptor-mediated endocytosis
  • Pinocytosis
  • Via Transporters
  • Channels
  • Carriers
  • Exocytosis
  • Transcytosis
• Passive diffusion


  Small, nonpolar molecules; hydrophobic molecules (estradiol, vit D); polar molecules <75 Da (water, ethanol, urea)
• Endocytosis


  Uptake of fluids or macromolecules by the cell
• Caveolae-mediated endocytosis


  Referred to as potocytosis or cellular sipping; certain small molecules (e.g., some vitamins) are taken up by invaginations of the membrane called caveolae; Caveolae: noncoated membrane invaginations with caveolin as the major structural protein; important in internalization of receptors and integrins
• Receptor-mediated endocytosis


  Bigger molecules bind to specific cell-surface receptors then internalized via an intracellular coat of clathrin proteins; discharge contents to early endosome
• Pinocytosis


  "Cellular drinking"; fluid-phase process → membrane invaginates and is pinched off to form a cytoplasmic vesicle; also begin at the clathrin-coated pit; discharge contents to early endosome
• Via Transporters


  Low molecular weight proteins (ions and molecules <1000 Da); often highly specific for a select molecule in each class (e.g., glucose but not galactose)
• Channels


  Hydrophilic pores; used when concentration gradients can drive solute movements; rapid movement of solutes; restricted by size and charge
• Carriers


  Bind the solute then undergo conformational changes with energy released by ATP; required when solute is moved against concentration gradient; slow transport
• Exocytosis


  Export of large molecules out of the cell; they are packaged within the RER and Golgi apparatus → concentrated in vesicles → fuse with the membrane → expel contents
• Transcytosis


  Movement of endocytosed vesicles between apical and basolateral compartments of cells; transport of intact proteins across epithelial barriers or for rapid movement of large volumes of solute
• Importance of the cell's cytoskeleton

  • It serves as the internal scaffolding of proteins; It allows the cell to adopt a particular shape, maintain polarity, organize the relationship of intracellular organelles, and move about
• Major classes of cytoskeletal proteins

  • Actin microfilaments
  • Intermediate filaments
  • Microtubules