Catabolism of Other Sugars - Fates of Pyruvate

OUTLINE: Glycogenolysis Glycolysis Introduction & overview; 2 phases Phase I Phase II Summary: labeling studies, logic, energetics Other sugars Pasteur: Anaerobic vs Aerobic (Fates of pyruvate) Fermentations (anaerobic) Rationale Lactate Acetoacetate decarboxylase Ethanol pyruvate decarboxylase alcohol dehydrogenase Catabolism of Other Sugars •Ingestion yields free glucose from glycogen and starch by a-amylase, maltase, and isomaltase •In the cell, glucose molecules are cleaved from glycogen and starch by glycogen phosphorylase. – yielding glucose 1-phosphate (and a little free Glc) – uses inorganic phosphate for lysis (phosphoro-lysis) •Disaccharides are hydrolyzed. – – – – lactose: glucose and galactose sucrose: glucose and fructose trehalose: glucose Monosaccharides fructose, galactose, and mannose enter glycolysis at different points. 1 Catabolism of Other Sugars Glc(a1àa1)Glc Gal(b1à4)Glc Glc(a1àb2)Fru Oligosaccharide Biosynthesis hexokinase MUSCLE LIVER UDP-mannose PGI hexokinase hexokinase a -Mannose 1-phosphate p ho sp ho m a n n o se m u ta se PFK-1 triose phosphate isom erase Aldolase/TIM Pyruvate Catabolism of Other Sugars ATP ADP Galactokinase Major cause of Galactosemia • Use of nucleotide sugars discovered by Argentinian biochemist Luis Leloir in 1940 for which he received the Nobel Prize. • Defects in the human genes for these enzymes causes what are called inborn errors in metabolism. • The cause of one of these due to galactose ingestion was one of the first discovered in 1956 by Herman Kalckar. • Galacotsemia causes enlarged liver, cirrhosis, kidney failure, cataracts, hypoglycemia, lethargy, and brain damage. Without treatment, mortality is about 75%. X • Defects in transferase are the underlying cause, with incidence of about 1:60,000 births. 2 Fates of Pyruvate Pasteur effect No Oxygen (anaerobic) +O 2à growth ↑ & fermentation ↓ sometimes anaerobic conditions Oxygen available (aerobic) In 1857, Louis Pasteur was studying fermentation by yeast, which are facultative anaerobes. They can produce energy with or without oxygen. When oxygen is low, the product of glycolysis, pyruvate, is turned into ethanol and carbon dioxide. When oxygen is high, pyruvate is converted to acetyl CoA and completely oxidized. More ATP is made aerobically than anaerobically. Therefore, about 15 times more glucose is consumed anaerobically as aerobically. Fates of Pyruvate Pasteur effect +O 2à growth ↑ & fermentation ↓ No Oxygen (anaerobic) In 1857, Louis Pasteur was studying fermentation by yeast, which are facultative anaerobes. They can produce energy with or without oxygen. When oxygen is low, the product of glycolysis, pyruvate, is turned into ethanol and carbon dioxide. When oxygen is high, pyruvate is converted to acetyl CoA and completely oxidized. More ATP is made aerobically than anaerobically. Therefore, about 15 times more glucose is consumed anaerobically as aerobically. The beginnings of biochemistry…… … Dr. Kornberg: Lecture 01.27.17 (2:52-9:22/11:27-13:30) 3 Fates of Pyruvate No Oxygen (anaerobic) sometimes anaerobic conditions Fermentation to acetate and other hydrocarbons in some strict anaerobes Fermentation: Why? • Regenerates NAD+ for further glycolysis under anaerobic conditions • Generation of energy (ATP) without consuming oxygen • Reduction of pyruvate to another product, there is no net change in oxidation state of the sugars • The process is used in the production of food from beer to yogurt to soy sauce. 2 Acetaldehyde 2 acetate 2 Ethanol Acetoacetate 4 Fates of Pyruvate No Oxygen (anaerobic) sometimes anaerobic conditions Fermentation to acetate and other hydrocarbons in some strict anaerobes Fermentation: Lactic acid • Pathway in animals • Reduction of pyruvate to lactate, reversible • Highly thermodynamically favorable/reversible (DG°’ = –6 kcal/mol) • During strenuous exercise, lactate builds up in the muscle. – generally less than 1 minute • The lactate can be transported to the liver and converted to glucose there. Called the Cori cycle. – Requires a recovery time – high amount of oxygen consumption to fuel gluconeogenesis – restores muscle glycogen stores 5 Fermentation: Lactic acid Mechanism Lactate dehydrogenase ① ② Stereo-specific ③ ④ ⑤ Acid catalysis Fates of Pyruvate No Oxygen (anaerobic) sometimes anaerobic conditions Fermentation to acetate and other hydrocarbons in some strict anaerobes 6 Fermentation: Acetoacetate decarboxylase P P Strict anaerobe: Clostridium acetobutylicum In 1916, the enzyme, acetoacetate decarboxylase, was discovered by Chaim Weizmann….. on to serendipity! Material for Exam 1 Ends 7