Chapt. 10 Cell Biology and Biochemistry Cell Chapt. 10 Cell Biology and Biochemistry The cell: Lipid bilayer membrane Student Learning Outcomes: Describe basic features of typical human cell Integral transport proteins Explain plasma membrane structure/ function Describe different transport proteins that permit compounds to cross the membrane Explain the structure and unique function of each organelle Describe the structure of the cytoskeleton Membrane-bound organelles sequester enzymes Cytoskeleton Different cell types have different amounts of organelles, enzymes Fig. 10.1 typical animal cell Mobility of phospholipids (Figure 2.23 Cooper et al) Phospholipid bilayer membrane Phospholipid bilayer membrane: Separates contents from external environment Lipid bilayers behave as 2-dimensional fluids: individual molecules can rotate and move laterally Fluidity determined by temperature, lipid composition. Asymmetric distribution of specific phospholipids Fig. 10.2 typical lipid bilayer 1
Phospholipids Glycerol lipids: 2 fatty acids, glycerol, phosphate; often polar group attached to phosphate Sphingolipids: 2 fatty acids, serine, phosphate Fig. 10.3 phospholipids and different head groups Figure 2.9 Cholesterol and steroid hormones Animal cell membranes contain cholesterol Hydrocarbon rings very hydrophobic, but -OH group is weakly hydrophilic, so cholesterol is amphipathic Cholesterol comes from diet or body synthesizes steroid hormones (e.g., estrogens and testosterone) are derived from cholesterol. Insertion of cholesterol in a membrane Ring structure of cholesterol helps determine membrane fluidity: Interactions between hydrocarbon rings and fatty acid tails makes membrane more rigid. Inserts near unsaturated fatty acids Cholesterol reduces interaction between fatty acids, maintains fluidity at lower temperatures. Fig. 10.4 Membrane proteins anchored to protein mesh Red blood cell is model membrane: no nucleus, organelles Integral proteins: (hydrophobic & hydrophilic regions) oftentransmembrane Channels Transporters Receptors Peripheral proteins: Bound to integral Signaling Structural Fig. 10.5 2
ABO, Structure of glycolipids Many cell membranes contain glycolipids: Sugar, fatty acids, no phosphate Also amphipathic Cholera toxin binds glycolipids ABO blood groups are glycolipids: Lipids & carbohydrates GPI anchors some extracellular proteins: Glycophosphatidyl inositol has sugar inositol on phospholipid Other lipids anchor proteins inside membrane Fig. 10.6 Phospholipid bilayer membrane Many carbohydrates are found on external surface of plasma membrane (glycocalyx) - protective Permeability of phospholipid bilayers Selective permeability of membrane allows cell to control its internal composition. Some molecules diffuse across bilayer: CO 2, O 2, H 2 O, Steroid hormones. Ions, larger uncharged, or polar molecules cannot diffuse across. Fig. 10.2 typical lipid bilayer 3
Proteins carry specific components Facilitative diffusion and transporter proteins Proteins transport most compounds across hydrophobic barrier of membranes Fig. 10.8 Fig. 10.7 Glucose transporter: Facilitative diffusion: Glucose moves down concentration gradient Insulin increases number of transporters Gated channels regulated by stimuli Gated channels are regulated by stimuli: voltage, ligand binding, phosphorylation CFTR (cystic fibrosis transmembrane conductance regulator) is a Cl- channel ATP binding domains regulated by phosphorylation mutated in cystic fibrosis Still passive transport since many Cl- for 1 ATP Active transport uses ATP to transport items Active transport: energy is used to transport items independent of concentration Primary: Na +, K + ATPase sets up major ion gradient (also Ca +2 /ATPase pump) Secondary: gradient is used to concentrate item (antiport, symport or cotransport) Fig. 10.10 Na+/K+/ATPase Fig. 10.9 4
Active transport cotransporter/antiport Lysosomes recycle components Active transport: Lysosomes have acid hydrolases: Symport: Glucose digest components, eliminate, recycle defects -> storage diseases (ex. Tay-Sachs) cotransporter let in Na+, glucose Intestinal cells Fig. 10.11 Antiport: Band 3 of red blood cell: Exchanges Cl- (in) for bicarbonate (out) Fig. 4.9, part Phagocytosis Endocytosis: cells take up macromolecules, fluids, and particles such as bacteria. Area of plasma membrane buds off inside cell to form vesicle with ingested material Phagocytosis (cell eating) occurs in specialized cell types. Autophagy recycles damaged organelles Pinocytosis (cell drinking) is a property of all eukaryotic cells. Fig. 10.12 Receptor-mediated Endocytosis Receptor-mediated endocytosis: mechanism for selective uptake of specific macromolecules. Cell surface receptors in regions (clathrin-coated pits). Pits bud as clathrin-coated vesicles, fuse to form lysosome 5
Endocytosis Receptor-mediated endocytosis first elucidated in patients with familial hypercholesterolemia lack LDL receptors on cell surface very high blood levels of cholesterol Mitochondria Mitochondria: powerhouses Have DNA, divide Two membrane layers Oxidative phosphorylation enzymes to make ATP Cholesterol transported in bloodstream mostly as low-density lipoprotein, LDL. 1500 cholesterols 800 phospholipids 1 protein Peroxisomes Peroxisomes: Single-membrane-enclosed organelles contain diverse metabolic enzymes (peroxins) Oxidative reactions, as fatty acid degradation Generate hydrogen peroxide (H2O2) No genome Fig. 10.13 One mitochondrion, Two mitochondria Nucleus Nucleus: DNA, genome 2-layer membrane Nuclear pores for transport Fig. 10.14 6
Endoplasmic reticulum Endoplasmic reticulum: RER (rough): ribosomes make proteins destined for modification, transport to Golgi, vesicles, secreted The Golgi Apparatus Distinct regions of Golgi: cis Golgi network receives molecules from ER medial and trans Golgi stacks most modifications here trans Golgi network sorting and distribution SER (smooth): enzymes make lipids, detoxify drugs Fig. 10.15 Cytoskeleton Cytoskeleton: Strength, shape, movement Microtubules α, β heterodimers Intermediate filaments Actin filaments Dynamic microtubules move organelles, vesicles, chromosomes Fig. 10.16 Actin filaments Actin fibers: Dynamic G-actin subunits (bound ATP) add to the F-actin polymer Provide shape Ex. under rbc membrane bound to spectrin (fig. 10.5) Muscle movement with myosin Fig. 10.17 7
Intermediate filaments Intermediate filaments IF: Strong fibers Ex. Keratin, nuclear lamins Mutated LMNA -> Hutchinson- Gilford Progeria premature aging Fig. 10.18 Key concepts Key concepts: Cell is basic unit of living organisms unique features define tissue functions Common feature is plasma membrane: phospholipid bilayer, semi-permeable Eukaryotes have intracellular organelles: Diverse structures and functions Clinical comments Dennis Veere - Cholera A toxin binds receptor, enters cell and moves with G protein Arf (ADPribosylation factor); modifies Gα-subunit of G protein, activates PKA, and the CFTR Cl - channel opens (Na + and Cl - and water exit; rapid efflux of water -> major diarrhea; give IV with Na +, glucose Lotta Topaigne - colchicine aided gout; blocks microtubules, derease phatogytosis, lysosomal enzymes and less inflammmation allopurinol decreases urate production Tay-Sachs - a lysosomal storage disease Review question Review question: Transmembrane proteins can best be described by which of the following? a. They can usually be dissociated from membranes without disrupting the lipid bilayer b. They are classified as peripheral membrane proteins c. They contain hydrophobic amino acid residues at their carboxy terminus. d. They contain hydrophilic amino acid residues extending into the lipid bilayer e. They contain membrane-spanning regions that are α-helices 8