Foundations of Biochemistry (Chap 1)

Transcription

1 Foundations of Biochemistry (Chap 1) Sections (Why this organization?): 1. Cellular 2. Chemical 3. Physical 4. Genetic 5. Evolutionary 1

2 Three questions to consider: 1. How does animate matter (living things) differ from inanimate matter? 2. What must living things do to stay alive? 3. How did we get from there to here (long/short scale)? 2

3 I. Cellular A. Why must all life have a cellular basis? (kinetics) 1. Plasma membrane (vinegar & oil salad dressing?) 2. Cytoplasm (a location) a) cytosol [150k x g supernantant] b) ribosomes & proteasomes (exercise & proteasomes?) [150k x g pellet] c) genetic info in nucleoid (prokaryotes) or nucleus (eukaryotes) B. Cell size/shape influenced by diffusion of good stuff in and waste products out. Cells are small. [1 to 100 μm] C. 3 major distinct organismal groupings: 1. Archaebacteria 2. Eubacteria See family tree, Fig Eukaryotes [Aside on O 2 use for #1-3] 3

4 Our family tree: See also: See Root of the Tree. Comment on refs.!!! 4

5 D. Different organisms use different types of energy sources & biosynthetic precursors. [energy & matter!] 1. Energy a) from light-phototrophs b) from high energy compounds-chemotrophs 2. Matter (all known life on our planet is carbon based) a) If you can start with CO 2, you re an autotroph. b) If not, you re a heterotroph Humans are: Redwood trees are: 5

6 E. Bacterial & archael cells have important similarities and differences: 1. Similar in complex outer membrane/wall structure See Fig Different in chemical details of #1 & ribosome structure (latter: early clue re. lineage differences) Comment re. ribosome structure regarding pro and eukaryotes. Clinical (pharmacological) relevance? 6

7 F. Eukaryotic cells have internal compartments (functions?), see Fig Comment on Fig 1-8 and methods. G. Eukaryotic cytoplasm is both highly ordered & dynamic. See Fig red = actin green = microtubules blue = chromosomes Animation, see: google: xvivo 7

8 Aside concerning complex nature of cytoplasm (vs. notion of watery cytosol: method influences ideas Three different filamentous proteins dominate: 1. Actin (motion of organelles and whole cells) 2. Microtubules (ditto re. #1) 3. Intermediate filaments (maintain structure, re-bar?) 4. #1-3 above are constantly de- and re-polymerizing (this is tightly regulated). 5. Endo/exocytosis depends partly on the cytoskeleton. 6. Cell division is quite dependent on filamentous polymers (see Fig 1-9b). 8

9 H. Cells build supramolecular structures, Fig How long is an average C!C bond? 2. How big (diameter) is hemoglobin? 3. How big is a ribosome? 4. How big is E. coli? 5. How big is the average rbc? 9

10 I. In vitro gives simplicity,... (In vivo gives...?) 1. Purification is good but... (now some molecules are lonely?) 2. Concentration of components is usually much lower in in vitro studies. See Fig. 1-12, The crowded cell 10

11 II. Chemical (review bond energies, hybridization, Lewis structures, CHM 111, 112, 331, etc.) A. Carbon compounds w/ lots of functional groups (Fig. 1-16, see next page). Geometry/rotation comments. B. Cells contain a universal set of small molecules 1. Intermediary metab (~ all organisms do these rxns.) 2. Secondary metabolism (specialized to specific organisms.) Examples: C. Macromolecules: the major parts of cells. 1. Nucleic acids 2. Proteins 3. Lipids 4. Carbohydrates See Table 1-1 on 2 nd page following. 11

12 D. Three dimensional structure: configuration and conformation. 1. Configuration? Isomers, types: Figs to 21. a) How did you do it in organic? b) A lot of the interesting biochemistry of carbohydrate monomers is based on diastereomer chemistry. 2. Conformation? See Fig (Animate?) a) Ethane low energy conformation is b) Ethane high energy conformation is c) Expand to a linear polymer with 600 covalent bonds. 12

13 E. Biomolecular interactions are stereospecific. 1. Why? Lefties? 2. Examples: 3. Nomenclature: Why not as much use of R and S as in organic? III. Physical (Thermodynamics, energy coupling, physical?) A. Steady State vs. Equilibrium for living things? B. Organisms transform energy and matter. In goes the good air, out goes the bad. 1. Energy: Why do you need it? 2. Matter: Why do you need it? C. Most of our energy comes from flow of e!. 13

14 D. Creating/maintaining order requires work. ΔG = ΔH!TΔS 1. Define each of the variables and make sure you know what is going on here. 2. More terms: endergonic, exergonic, same re.-thermic 3. If you are having trouble with entropy, see Box 1-3. Asides: 1. What is the 2 nd Law of Thermodynamics? 2. Almost all of the jobs done in your body are managed by large, complicated high-energy molecules. You can t make these without a supply of energy. 14

15 E. Energy coupling links rxns. 1. What is up with windmills? Waterwheels? Etc.? 2. Why do we do it? See Fig. 1-27, next page. More here than meets the eye!!! A coupled rxn. you are running right now: 3. How do you define equilibrium? Comment on Reaction Coordinate Diagrams. F. What do K eq and ΔG 0 tell you about a rxn.? Can you derive ΔG 0 =!RT ln K eq from eq. 1-1? 15

16 G. Enzymes promote sequences of chemical rxns. Consider: See Fig Different paths taken Energy surfaces (pin ball?) H. Metabolism is regulated to achieve balance & economy. i.e., Efficient organisms regulate their metabolic pathways. Inefficient organisms are replaced by efficient ones. Example of a regulated pathway: 16

17 IV. Genetics (Why are you like your mom and dad? Can those children possibly be related to me?) A. Genetic continuity comes from our DNA B. The structure of DNA allows for nearly perfect replication and repair. Fig 1-31 C. Linear DNA sequences encode (RNA &) protein sequences (via mrna sequences). See Fig Completely aside See: Finding your roots at pbs.org Wanda Sykes/John Legend episode 17

18 V. Evolution (Fuzzier at 1st [in more ways than one], but sharper as we get closer to the present. How sharp are the Cambrian flowers?) A. Changes in DNA allow evolution to occur (from above: nearly perfect?) B. Pre-life biomolecules probably arose through chemical evolution. 1. In the lab: Miller & Urey. 2. Naturally: extreme environments? 18

19 C. RNA (or similar) may have been 1 st genes and catalysts (enzymes?). D. Biological evolution began more than years ago. Comments re. Age of the earth/universe. E. The first cell probably used inorganic fuels. Has there always been lots of O 2 for oxidizing reduced compounds? G. Eukaryotes evolved from prokaryotes, eventually. See Fig

20 H. Molecular anatomy (usually sequence information) reveals evolutionary relationships. 1. Between organisms 2. Between proteins 3. Comment on homologs, paralogs, and orthologs a) genes with similar sequences are homologous b) distinct homologous genes within the same species are called parolgous. Implications re. gene duplication and mutation. (New information...the globin genes.) c) genes in different species that have similar sequences are called orthologs. If the function of the gene is known in one species it may be possible to draw inferences about the function of the gene in the second species. 20

21 I. Functional genomics: process based organization of the genome. J. Medical significance of genomics??? Evolution and Disease by Dr. Steven Stearns (Yale) (You can skip the 4 minute intro if you want.) The file format is.f4v. To play this file I had to download the FLV player (It is free.) at: 21