Lecture 6 Slides rh Go to TA sections; challenge them! Come to R’s and/or TAs office hours 2130 Pac Hall Mon 2-3 Tue 2-3 details on course web site: http://course.ucsd.edu/rhampton/bibc102 Warburg Effect the Warburg effect is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol Otto Heinrich Warburg 1931 Nobel Prize in Medicine Warburg Effect Getting other sugars into the glycolytic pathway fig 14-10 A second route for fructose (in liver) pg 545 Glycogen: nature’s sugar bowl Liberating glucose units from glycogen fig 14-11 more about glycogen later From glycogen to glycolysis… phosphoglucomutase another mutase… Now what? fig 14-1 Now what? fig 14-1 Now what? Fermentation: anaerobic metabolism of glucose without oxidation... fig 14-1 LDH converts pyruvate to lactate, restoring the pool of NAD+ pg 547 LDH converts pyruvate to lactate, restoring the pool of NAD+ pg 547 ethanol production: another NAD+ restoration strategy pg 547 Thiamine pyrophosphate (TPP): an activated carbon fig 14-14 Thiamine pyrophosphate in ethanol production fig 14-14 TPP as a carbanion nucleophile in pyruvate metabolism fig 14-14 TPP as a carbanion nucleophile in pyruvate metabolism fig 14-14 TPP as a carbanion nucleophile in pyruvate metabolism fig 14-14 TPP-mediated enzymatic reactions TPP is all about carbonyl activation table 14-1 The glycolysis energy landscape (pyruvate set to 0) Regulated glycolytic enzymes hexokinse (and glucokinse) regulated by G6P allosterically liver isozyme is glucokinase, different phosphofructokinase (PFK-1) pyruvate kinase regulated by ATP, citrate, and fatty acids The glycolysis energy landscape (pyruvate set to 0) regulation of hexokinase: isozymes can differ fig 15-12 PFK-1 : a right fancy enzyme! fig 15-14 PFK-1: allosteric regulation by ATP, etc… fig 15-14 PFK-1: allosteric regulation by ADP, etc… xxx FPK-1 has multiple allosteric regulators fig 15-14 Our book’s notation for regulators inhibition fig 15-14 activation PFK-1 has multiple allosteric regulators fig 15-14 Pentose phosphate pathway oxidative reactions fig 14-21 Glucose as a source of other stuff Pentose phosphate pathway oxidative reactions fig 14-21 Pentose phosphate pathway oxidative reactions fig 14-21 Pentose phosphate pathway oxidative reactions fig 14-21 Pentose phosphate pathway: non-oxidative rxns all movement of carbonyl groups to and fro… fig 14-22 Pentose phosphate pathway: nonoxidative reactions 2C 3C 2C 2C 2C fig 14-22 3C end of lecture 6 LDH converts pyruvate to lactate, restoring the pool of NAD+ pg 547