D’YOUVILLE COLLEGE PMD 604 - ANATOMY, PHYSIOLOGY, PATHOLOGY II CELL BIOLOGY I Lecture 1: Endomembrane system, Energetics G & H chapter 2 & parts of chapters 67 - 69 1. Introduction: • physicochemical system: - cells are highly organized, highly improbable, living systems that operate a 'steady state' relationship with their environment, obeying laws of basic chemistry and physics (physicochemical systems) - the high degree of order requires energy to maintain it, since the overall tendency of the universe is to increase disorder (entropy) - cellular homeostasis (constant conditions) employs a steady state or flowthrough system that avoids establishment of chemical equilibrium (which is a state of no change = no work) (ppt. 1) - cellular metabolism (collective reactions) includes both energy-yielding (exergonic) reactions (ppt. 2) and energy-requiring (endergonic) reactions; by coupling reactions (ppts. 3 & 4), cells channel energy from the environment towards maintenance of an exquisite orderly system 2. Chemicals of a normal cell • inorganic – water (milieu for metabolic reactions, participant in some reactions, product of some reactions) - ions (activators of enzymes, maintenance of osmotic balance, basis for electrical properties of cell membranes) • organic - proteins – polymers of amino acids; provide structural components of cytoskeleton & extracellular fibrous components (e.g. tendons, ligaments), provide motility, provide membrane transport, provide enzymes & specific receptor molecules - lipids – include phosphoglycerides & cholesterol (constituents of cell membranes), include triglycerides (storage of energy) - carbohydrates – especially glucose and glycogen, provide energy - nucleic acids – hereditary information & genetic implementation 3. Organelles (fig. 2 – 2)(ppt. 5): • plasma membrane (fig. 2 – 3) (ppt. 6): selective permeability; controls interaction with cellular environment; consists of phosphoglyceride bilayer fortified by cholesterol (fluid matrix) and proteins (mosaic) that 'float' in or on the fluid matrix; fluid-mosaic model accounts for transport of materials across membrane (permeability), signal reception, cell-cell binding & cell recognition (ppt. 7) - diffusion (channels or lipid bilayer) PMD 604 - lec 1 - p. 2 - - carrier-mediated transport (protein shuttles) - active transport (carriers energized by ATP) - endocytosis (phagocytosis & pinocytosis) (fig. 2 – 11 & ppt. 8) - exocytosis (secretion & excretion) - receptors: signal transduction, cellular recognition, & specific endocytosis PMD 604 - lec 1 - p. 3 - • mitochondrion (fig. 2 – 7 & ppt. 9): ‘powerhouse of the cell’ (provides energy – synthesis of ATP) - enzymes of Krebs cycle & electron transport (figs. 67 – 6, 67 – 7 & ppt. 10) - enzymes of fatty acid oxidation (fig. 68 – 2) • endoplasmic reticulum (figs. 2 – 4 & ppt. 11): smooth & rough – site of biosynthesis reactions - enzymes of protein synthesis (ribosomes of rough ER) - enzymes of lipid biosynthesis; enzymes of detoxification reactions (smooth ER) • Golgi apparatus (fig. 2 – 5 & ppt. 12): modification & distribution of synthesized products - formation of lysosomes • lysosome (fig. 2 – 12 & ppt. 13): bag of digestive enzymes; role in endocytosis, role in removal of endocytic damage • cytoskeleton (ppt. 14): maintenance of cell shape & regulation of movement in the cell (fig. 2 - 17 & ppt. 15) • nucleus (ppt. 16): stores genetic material; provides genetic control of cell activities 3. Endomembrane System: (pp. 20 – 22, fig. 2 – 13 & ppt. 17) • nuclear envelope and ER (sites of biosynthesis – product enters cistern) • transport vesicles pinch off from ER, migrate to Golgi apparatus; movement of organelles or other materials through cytoplasm is facilitated by microtubules (ppt. 18) • Golgi apparatus – cis face (nuclear side) accepts transport vesicles (fusion); biosynthesized product modified as it passes through • secretion vesicles or lysosomes pinch off from trans face (cell membrane side) of Golgi apparatus Energy Metabolism – Mitochondria: (figs. 2 – 7, 2 – 14 & 2 – 15 + selected parts of chapters 67, 68 & 69) 4. • ATP – cell’s energy currency (p. 21, fig. 67 – 2 & ppt. 19); contains energyrich bonds • oxidation-reduction – oxidation = loss of electrons from a substrate (exergonic); reduction = gain of electrons by a substrate (endergonic); oxidation & reduction must always occur together (ppt. 20) - energy from oxidations drives ATP synthesis via oxidative phosphorylation - stepwise oxidations (dehydrogenations) remove electrons with hydrogens from a substrate; carriers of these high-energy electrons include NAD (pp. 813 – 814 & ppt. 21) or FAD - energy from active metabolic intermediates drives ATP synthesis via substrate level phosphorylation (ppt. 22) PMD 604 - lec 1 - p. 4 - - some reactions occur in the cytosol; majority occur within mitochondrion (ppt. 23) PMD 604 - lec 1 - p. 5 - • glycolysis (fig. 67 – 5 & ppt. 24) – initial stepwise oxidation of glucose (occurs in cytosol) - two phases: energy investment phase – uses 2 ATP to activate glucose - energy payoff phase – 6-C sugar split into two 3-C molecules, oxidized (2 reduced NAD formed), 4 ATP formed (net gain of 2), ends with 2 pyruvic acids - aerobic vs. anaerobic pathways (ppt. 25) – with oxygen present (aerobic condition), pyruvic acid is converted to acetyl CoA (in mitochondrion) to enter Krebs cycle; in absence of oxygen (anaerobic pathway), need to restore NAD (oxidized) is fulfilled by reduction of pyruvic acid to lactic acid • Krebs cycle (fig. 67 – 6 & ppt. 26) – within mitochondrion, 2 acetyl CoAs (2C molecule) are formed by oxidation (2 reduced NADs formed) and removal of 2 carbon dioxides from 2 pyruvic acids; acetyl CoA is donor to Krebs cycle - each acetyl CoA combines with a 4-C acceptor acid to form a 6-C acid (citric acid); 6-C acid progresses through two dehydrogenations (2 reduced NADs formed) and two decarboxylations (CO2 removal) to form an energy-rich 4-C acid (succinyl CoA), which provides energy for ATP synthesis; resulting 4-C acid progresses through two further dehydrogenations (reduced NAD & reduced FAD formed) to regenerate 4-C acceptor (ready to combine with another acetyl CoA) - overall energy yield/glucose (2 acetyl CoAs): 6 reduced NADs, 2 reduced FADs & 2 ATPs + 2 more reduced NADs (from pyruvic acid oxidation) (ppt. 27) • oxidative phosphorylation (fig. 67 – 7 & ppts. 28 & 29) – high-energy electrons (from reduced NAD & from reduced FAD) pass through a chain of enzymes, giving up their energy to drive ATP synthesis (phosphorylation); final electron acceptor is oxygen, which combines with hydrogen ions to form water - each reduced NAD furnishes enough energy to produce 3 ATPs (fig. 67 – 7 & ppt. 29) - each reduced FAD furnishes enough energy to produce 2 ATPs • fatty acid oxidation (fig. 68 – 2 & ppt. 30) – larger energy yield/gram than glucose; large quantities of acetyl CoA removed by formation of ketone bodies (p. 844) • oxidative deamination and urea formation (ppt. 31) – mechanism for oxidation of amino acids yields reduced NAD & ammonia; ammonia is converted to urea for excretion • uses for ATP (fig. 2 – 15 & ppt. 32) – provides energy for transport, for motility & for biosyntheses