BL 424 Chapter 3: Review Cell Metabolism Student learning outcomes: 1. to recall the central role of enzymes as catalysts and the role of coenzymes such as NAD+/NADH in carrying electrons from redox reactions 2. to explain that ATP is the cell's energy currency, derived as metabolic energy from the breakage and rejoining of covalent bonds through processes that include glycolysis, citric acid (Kreb's) cycle, and electron transport chain. 3. to briefly review the biosynthesis of cell macromolecules, 4. to state briefly how photosynthesis converts energy from the sun to ATP and organic molecules. Important figures are: 1*, 2, 3, 5, 6*, 8*, 9**, 10, 11, 12, 13, 14, 17, 18, 23, 25 Important tables are: 1 1. Enzymes are biological catalysts Proteins perform most catalysis (Fig. 2) (but some enzymes are RNA molecules - ribozymes) Enzymes facilitate reactions under mild conditions: They lower activation energy and increase rate (Fig. 3.1) Binding of substrate to enzyme induces conformational change (induced fit) (Fig. 3.3) Substrate(s) is (are) converted to product(s) Amino acids at the active site pocket catalyze the reaction (Fig. 3.5) Ex. Of chymotrypsin hydrolyzes peptide bond Coenzymes include NAD+ ->NADH; (Fig. 3.6*) NAD+ is an electron carrier that works with enzymes in biological oxidation-reduction reactions (Redox) S1(red) + S2(ox) -> S1(ox) + S2(red) NAD+ accepts 2 electons and 1 H+ from 1 substrate and transfers them to another substrate other coenzymes include RAD, vitamin derivatives (Table 1) Enzyme activity can be regulated (positively or negatively) by: Feedback inhibition –end product of pathway (Fig. 3.7) binds and inhibits first enzyme of path allosteric regulation (compound binding not at active site causes conformational change in enzyme; Fig. 3.8) other proteins binding to an enzyme can affect activity*** covalent modifications such as phosphorylation (PO4-) on –OH groups of ser, thr or tyr residues (Fig. 3.9*) affect activity; Sometimes Phosphates activate, sometimes inhibit Kinases add phosphates (protein kinases add PO4 to proteins) Phosphatases remove phosphates Reversible phosphorylation is important for signaling molecules, For responses of cells to extracellular signals like hormones Ex. Epinephrine activation of phosphorylase kinase to start glycogen breakdown (Fig. 9) 3.2. ATP is energy currency, continually produced and used: ATP is required for biosynthetic reactions (ATP -> ADP + Pi gives off 7.3 kcal) which can be coupled to biosynthetic reactions that require energy: (Fig. 3.10,11) (ex. glucose + P -> glucose-6-P) Recall basic features of energy generating pathways, (make and break covalent bonds) and cellular compartments for these paths: Glycolysis is common to most cells (Fig. 3.11) – does not require oxygen Net reaction: Glucose -> pyruvate + 2 ATP + 2 NADH Costs 2 ATP to start reaction Fermentation recycles NADH to NAD+; does not require oxygen (Fig. 3.11); occurs in cytoplasm produces lactate (animals), CO2 + ethanol (yeast) An organic molecule of the pathway is the terminal electron acceptor Wasteful process, not get much of energy of glucose Aerobic respiration (oxidative phosphorylation) involves: pyruvate oxidation, citric acid (Kreb's), electron transport chain oxygen is the terminal electron acceptor -> H2O + CO2 produces the most ATP per glucose; complete oxidation common to animals, many prokaryotes (Figs. 3.12, 3.13, 3.14) Occurs in mitochondria in animals some prokaryotes can do anaerobic respiration: pyruvate oxidation, citric acid (Kreb’s), electron transport chain (an inorganic molecule (not O2) is the terminal electron acceptor) Ex. E. coli can use NO3= as acceptor Other organic molecules can provide energy: fatty acid oxidation degrades organic molecules in 2-Carbon pieces (Fig. 3.15); 16-C fatty acid -> 138 ATP [photosynthesis (light and dark reactions; Fig. 3.17)] in plants, some prokaryotes, chlorophyll & pigments convert energy of sun and CO2 plus H2O to organic molecules (via NADPH, ATP) (Fig. 18) Light reactions provide energy of ATP, NADPH, form O2 from H2O Dark reactions form sugars3.3. Biosynthesis of cell components requires energy Gluconeogenesis (synthesis of glucose from pyruvate) is not exactly the reverse of glycolysis (Fig. 3.19) Gluconeogenesis requires ATP, GTP, NADH Polysaccharide synthesis (Carbohydrate polymerization) utilizes ATP and UTP-driven reactions: UCP-glucose is an activated intermediate (Fig. 3.20) Lipids are energy storage molecules & major components of membranes. Lipids are synthesized in 2-C units from Acetyl CoA (derived from breakdown of carbohydrates); Lipid biosynthesis requires ATP and NADH, Resembles reverse of fatty acid breakdown Amino acids are derived by addition of NH2 to intermediates of glycolysis and citric acid cycle (Fig. 3.22) Protein synthesis joins amino acids in peptide bonds In an order specified by the sequence of bases in DNA (via mRNA) Genetic code: tRNA carrying aa binds to mRNA at codon; Ribosome catalyzes peptide bond between adjacent aa ATP is required to join each amino acid to its tRNA (aminoacyl-tRNA); GTP also required (Fig. 3.23) 1st amino acid is N-terminus; last one is COOH-terminus Nucleotides are synthesized from 5-Carbon sugars and amino acid precursors; rNTPs are converted to the dNTPs Nucleic acids are synthesized with 5’ phosphate of nucleoside triphosphate (NTP) of incoming monomer joined onto 3' OH of sugar of the growing chain; 5’-> 3’ (Fig. 3.25) Review: Review the general features, Don’t worry too much about the detail, as we will do detail later. *Note which compartment of eukaryotic cell is used for which reactions. Focus on animal cells, not photosynthesis of plants Most relevant questions at end of chapter: 1-4,