Week 8 Synchronous Lecture: The Fate of Pyruvate and Gluconeogenesis PDF

Week 8 – Synchronous Lecture The Fate of Pyruvate and Gluconeogenesis Kimchi is a fermented food generated by microorganisms via anaerobic glycolysis. Lactate is produced during this process, which...

Week 8 – Synchronous Lecture The Fate of Pyruvate and Gluconeogenesis Kimchi is a fermented food generated by microorganisms via anaerobic glycolysis. Lactate is produced during this process, which functions as a preservative. Metabolism of other Hexoses Metabolism of other Hexoses Galactokinase “Leloir” pathway Hexokinase Hexokinase (in muscle) (in liver) Fructose and Obesity potential mechanisms: bypass of PFK regulatory step generation of glycerol-3- phosphate (liver)  precursor to triglycerides! Fed Glycogen Metabolism Digestion Gluconeogenesis Glycolysis Hungry Glucose ⇢ Glucose 6-phosphate ⇢ ⇢ ⇢ ⇢ Pyruvate + ATP Glycogenolysis Glycogen Synthesis Glycogen Normal level of blood glucose: 80-110 mg/dL  Gluconeogenesis Brain and red blood cells can only use glucose as fuel. fasting: 1. use glucose in blood 2. use glycogen in liver 3. make glucose from non-carbohydrate precursors  gluconeogenesis occurs mainly in the liver, to a limited extent in the kidneys question: Can we simply reverse the reactions of glycolysis?  Gluconeogenesis many enzymes are shared between glycolysis and gluconeogenesis  pathways need to take place in the same location inside cells cytosol! Gluconeogenesis problem: “irreversible reactions”  need to circumvent them  use different reactions  Gluconeogenesis four “new” enzymes bypass three thermodynamically unfavorable reactions: pyruvate carboxylase phosphoenolpyruvate carboxykinase fructose bisphosphatase glucose-6-phosphatase  Glucose-6-phosphatase and fructose bisphosphatase first and third reactions of glycolysis (catalyzed by kinases)  irreversible reactions need new enzymes that remove phosphate groups: phosphatases reaction type: hydrolysis Conversion of pyruvate to phosphoenolpyruvate pyruvate can be made from lactate (homolactic fermentation!) oxaloacetate is a breakdown product of amino acids (except Leu and Lys)  expense: 2 ATP per PEP!  Glycolysis and Gluconeogenesis If glycolysis and gluconeogenesis occurred simultaneously, there would be a net consumption of ATP! Goal of producing ATP would be futile! “futile reaction cycles” Instead, glycolysis and gluconeogenesis regulated based on the cell’s needs glycolysis ON  gluconeogenesis OFF gluconeogenesis ON  glycolysis OFF remember: glycolysis is regulated by fructose-2,6-bisphosphate  Gluconeogenesis is regulated at the fructose bisphosphatase step a single compound can control flux through two opposing pathways in a reciprocal manner avoidance of a “futile reaction cycle”, just wasting ATP Activity W8L_1 The Fate of Pyruvate fermentation  Homolactic Fermentation during strenuous exercise, pyruvate is temporarily converted to lactate  recycling of NAD+ to sustain glycolysis  Alcoholic Fermentation In the absence of oxygen, certain organisms (yeast) convert pyruvate to ethanol and CO2 in two steps.  again: recycling of NAD+ to sustain glycolysis  baking  beer- and winemaking  Alcohol Consumption physiological effects of alcohol: central nervous system depressant, psychoactive drug breakdown of alcohol (2 steps): “hangover” compounds methanol poisoning: ethanol as antidote  prevents methanol processing!  methanol excreted before formaldehyde and formic acid are generated! Structure of Acetyl-CoA The structure of the PDC PDC cofactors / prosthetic groups Reactions catalyzed by the PDC  lipoamide and acetyl-CoA https://www.youtube.com/watch?v=NjQSxcxOVQI PDC control by product inhibition PDC control via E1 phosphorylation Activity W8L_2 Activity: W8L_3