《生物化学》课程PPT教学课件（英文版）Chapter 15 Glycolysis and the Catabolism of Hexoses

Chapter 15 Glycolysis and the catabolism of Hexoses

Chapter 15 Glycolysis and the Catabolism of Hexoses

An overview on D-glucose metabolism The major fuel of most organisms, G0=2840 kJ/mole if completely oxidized to co2 and h,o via the glycolysis pathway, citric acid cycle and oxidative phosphorylation (generating ATP) Can also be oxidized to make nadph and ribose-5-P via the pentose phosphate pathway Can be stored in polymer form(glycogen or starch) or be converted to fat for long term storage Is also a versatile precursor for carbon skeletons of almost all kinds of biomolecules, including amino acids nucleotides, fatty acids, coenzymes and other metabolic intermediates

An overview on D-glucose metabolism • The major fuel of most organisms, G' o = –2840 kJ/mole if completely oxidized to CO2 and H2O via the glycolysis pathway, citric acid cycle and oxidative phosphorylation (generating ATP) . • Can also be oxidized to make NADPH and ribose-5-P via the pentose phosphate pathway. • Can be stored in polymer form (glycogen or starch) or be converted to fat for long term storage. • Is also a versatile precursor for carbon skeletons of almost all kinds of biomolecules, including amino acids, nucleotides, fatty acids, coenzymes and other metabolic intermediates

1. The Development of biochemistry and the Delineation of Glycolysis Went Hand by hand 1897, Eduard Buchner( Germany), accidental observation: sucrose(as a preservative) was rapidly fermented into alcohol by cell-free yeast extract The accepted view that fermentation is inextricably tied to living cells(i.e, the vitalistic dogma )was shaken and biochemistry was born: metabolism became chemistry 1900s, Arthur Harden and William Young Pi is needed for yeast juice to ferment glucose, a hexose diphosphate(fructose 1, 6-bisphosphate)was isolated

1. The Development of Biochemistry and the Delineation of Glycolysis Went Hand by Hand • 1897, Eduard Buchner (Germany), accidental observation : sucrose (as a preservative) was rapidly fermented into alcohol by cell-free yeast extract. • The accepted view that fermentation is inextricably tied to living cells (i.e., the vitalistic dogma) was shaken and Biochemistry was born: Metabolism became chemistry! • 1900s, Arthur Harden and William Young Pi is needed for yeast juice to ferment glucose, a hexose diphosphate (fructose 1,6-bisphosphate) was isolated

1900s, Arthur Harden and William Young(Great Britain separated the yeast juice into two fractions one heat-labile, nondialyzable zymase(enzymes) and the other heat-stable dialyzable cozymase (metal ions, ATP, ADP, NAD) 1910s-1930s, Gustav Embden and otto meyerhof (Germany), studied muscle and its extracts Reconstructed all the transformation steps from glycogen to lactic acid in vitro; revealed that many reactions of lactic acid(muscle) and alcohol(yeast) fermentations were the same Discovered that lactic acid is reconverted to carbohydrate in the presence of o2(gluconeogenesis) observed that some phosphorylated compounds are energy-rich

• 1900s, Arthur Harden and William Young (Great Britain) separated the yeast juice into two fractions: one heat-labile, nondialyzable zymase (enzymes) and the other heat-stable, dialyzable cozymase (metal ions, ATP, ADP, NAD+ ). • 1910s-1930s, Gustav Embden and Otto Meyerhof (Germany), studied muscle and its extracts: – Reconstructed all the transformation steps from glycogen to lactic acid in vitro; revealed that many reactions of lactic acid (muscle) and alcohol (yeast) fermentations were the same! – Discovered that lactic acid is reconverted to carbohydrate in the presence of O2 (gluconeogenesis); observed that some phosphorylated compounds are energy-rich

(Glycolysis was also known as Embden Meyerhof pathway The whole pathway of glycolysis(Glucose to pyruvate) was elucidated by the 1940s

• (Glycolysis was also known as Embden￾Meyerhof pathway). • The whole pathway of glycolysis (Glucose to pyruvate) was elucidated by the 1940s

The Nobel Prize in Chemistry 1907 for his biochemical researches and his discovery of cell-free fermentation Eduard Buchner Germany Landwirtschaftliche Hochschule (Agricul tural College) Berlin, Germany 1860-1917

The nobel Prize in Chemistry 1929 for their investigations on the fermentation of sugar and fermentative enz ymes Presentation Speech Sir Arthur Harden Great Britain London University London Great Britain 1865-1940 Hans von Euler-Chelpin Stockholm University Stockholm, Sweden 1873-1 Biography am

The Nobel Prize in Physiology or Medicine 1922 Presentation Speech for his discovery relating to the production of heat in the muscLe Sir Archibald Vivian Hill Great Britain London University London, Great Britain 1977 Biography for his discovery of the fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle Otto Fritz Meyerhof Kiel University Kiel, Germany 1884 Biography

2. The overall glycolytic pathway can be divided into two phases The hexose is first phophorylated(thus activated) and then cleaved to produce two three-carbon intermediates at the preparatory phase, consuming atP The three-carbon intermediates are then oxidized during the payoff phase, generating ATP and Nadh All intermediates are phosphorylated(as esters or anhydrides with six(derivatives of Glucose or Fructose)or three carbons( derivatives of dihydroxyacetone, glyceraldehyde, glycerate,or pyruvate)

2. The overall glycolytic pathway can be divided into two phases • The hexose is first phophorylated (thus activated) and then cleaved to produce two three-carbon intermediates at the preparatory phase, consuming ATP. • The three-carbon intermediates are then oxidized during the payoff phase, generating ATP and NADH. • All intermediates are phosphorylated (as esters or anhydrides) with six (derivatives of Glucose or Fructose) or three carbons (derivatives of dihydroxyacetone, glyceraldehyde, glycerate, or pyruvate)

Six types of reactions occur: group transfer (kinase), isomerization(isomerase), aldol cleavage (aldolase), dehydrogenation( dehydrogenase) group shift(mutase), dehydration(dehydratase or enolase Ten steps of reactions are involved in the pathway. Only a small fraction( 5%)of the potential energy of the glucose molecule is released and much still remain in the final product of glycolysis, pyruvate All the enzymes are found in the cytosol(pyruvate will enter mitochondria for further oxidation)

• Six types of reactions occur: group transfer (kinase), isomerization (isomerase), aldol cleavage (aldolase), dehydrogenation (dehydrogenase), group shift (mutase), dehydration (dehydratase or enolase). • Ten steps of reactions are involved in the pathway. • Only a small fraction (~5%) of the potential energy of the glucose molecule is released and much still remain in the final product of glycolysis, pyruvate. • All the enzymes are found in the cytosol (pyruvate will enter mitochondria for further oxidation)