* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Metabolism - Glycolysis
Biosequestration wikipedia , lookup
Amino acid synthesis wikipedia , lookup
Fatty acid metabolism wikipedia , lookup
Metalloprotein wikipedia , lookup
Isotopic labeling wikipedia , lookup
Light-dependent reactions wikipedia , lookup
NADH:ubiquinone oxidoreductase (H+-translocating) wikipedia , lookup
Multi-state modeling of biomolecules wikipedia , lookup
Nicotinamide adenine dinucleotide wikipedia , lookup
Basal metabolic rate wikipedia , lookup
Biosynthesis wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Metabolic network modelling wikipedia , lookup
Phosphorylation wikipedia , lookup
Photosynthesis wikipedia , lookup
Microbial metabolism wikipedia , lookup
Adenosine triphosphate wikipedia , lookup
Oxidative phosphorylation wikipedia , lookup
Photosynthetic reaction centre wikipedia , lookup
Metabolism - Glycolysis Voet & Voet: Chapter 11 Lecture 16 Biochemistry 2000 Slide 1 Glycolysis Metabolism Metabolism is the complete set of chemical reactions that allow cells to grow and divide. Metabolic processes are divided into: (1) Catabolism (eg glycolysis) – reactions that breakdown complex molecule into simple compounds AND yield energy (2) Anabolism (eg gluconeogenesis) – reactions that create complex molecule from simple compounds AND utilize energy Lecture 16 Biochemistry 2000 Slide 2 Glucose Metabolism There are three pathways that utilize the majority of glucose in almost all cells Glycolytic and pentose phosphate pathways breakdown the majority of glucose Lecture 16 Biochemistry 2000 Slide 3 Glycolysis Glycolysis is a series of 10 enzyme catalyzed reactions that converts -D-glucose into pyruvate and energy (2 ATP and 2 NADH) Reactions 1-5 (Energy-investing or preparatory phase) ● 2 ATP are consumed as glucose (6 carbons) is converted to a form that can be split into two 3 carbon compounds Reactions 6-10 (Energy-generating or payoff phase) ● 2 ATP and 1 NADH are generated as each 3 carbon compound is dephsphorylated Blue = Carbon Purple = Phosphate Lecture 16 Biochemistry 2000 Slide 4 Glycolysis II. Glycolytic pathway showing structures of all substrates and products ● ● Glycolytic enzymes are listed on the far right Important reaction are indicated by boxed text on the left – Includes all reactions that consume or generate energy – Includes cleavage of 6 carbon sugar into 3 carbon sugars Lecture 16 Biochemistry 2000 Slide 5 Energy Yield per Glucose Sequential reactions sharing a common intermediate have standard free energy changes that are additive (coupling) Glucose Degradation Glucose + 2NAD+ → 2 pyruvate + 2NADH + 2H+ ∆G’1O= -146 kJ/mol ATP Formation 2ADP + 2Pi → 2ATP + 2H2O ∆G’2O= 61.0 kJ/mol ---------------------------------------------------------------------------------------------------------Overall Reaction Glucose + 2NAD+ + 2ADP + 2Pi → 2pyruvate + 2NADH + 2H+ + 2ATP + 2H2O ∆G’SO= ∆G’1O + ∆G’2O = -85 kJ/mol Lecture 16 Biochemistry 2000 Slide 6 Glycolytic Enzymes Kinases are enzymes that transfer a phosphoryl group from a high energy donor to an acceptor (ie. consume or produce ATP) – Reaction 1 and 3 consume ATP – Reactions 7 and 10 produce ATP Isomerases and Mutases are enzymes that catalyze internal structural rearrangements (no net gain or loss of atoms) – Reactions 2 and 5 are catalyzed by isomerases (carbonyl isomerization) – Reaction 8 is catalyzed by a mutase (phosphate changed position) Remaining enzymes are all interesting/special Aldolase – splits 6 carbon sugar into a pair of 3 carbon sugars Dehydrogenase – produces NADH (energy) Enolase – produces phosphoenolpyruvate (a very high energy compound) Lecture 16 Biochemistry 2000 Slide 7 Hexokinase Reaction 1: First ATP Utilization Transfer of phosphoryl group from ATP to the O6 of glucose Enzyme undergoes conformational change upon substrate binding Excludes water and allows reaction to proceed ∆ G’° = -16.7 kJ/mol Lecture 16 Biochemistry 2000 Slide 8 Phosphoglycerate Kinase Reaction 7: First substrate level phosphorylation Like hexokinase – two lobes swing together, exclude water and allow phosphorylation ∆G’° = -18.5 kJ/mol Note: all phosphoryl transfer reactions have large negative ∆G’° changes as high energy bonds are being broken ● Lecture 16 These reaction drive glycolysis Biochemistry 2000 Slide 9 Glucose-6-Phosphate Isomerase Reaction 2: Reversible isomerization of G6P to F6P ● aldose to ketose isomerization ● prepares 6 carbon sugar for further phosphorylation Isomerization ∆G’° = 1.7 kJ/mol Lecture 16 Biochemistry 2000 Slide 10 Triose Phosphate Isomerase Reaction 5: Rapid, reversible isomerization of DHAP to G3P ● ketose to aldose isomerization Only G3P can continue down the glycolytic pathway ∆G’° = 7.5 kJ/mol Isomerase and mutase reaction generally have small or positive ∆G’° changes ● Reactions are driven by constant removal of product Lecture 16 Biochemistry 2000 Slide 11 Aldolase Aldolase catalyzes cleavage of the 6 carbon sugar to a pair of 3 carbon sugars (Reaction 4) ● Complex 4 step mechanism glyceraldehyde-3-phosphate (G3P) fructose-1,6-bisphosphate (FBP) dihydroxyacetone phosphate (DHAP) ∆G’° = 23.8 kJ/mol Lecture 16 Biochemistry 2000 Slide 12 Glyceraldehyde-3-phosphate dehydrogenase Reaction 6: Oxidation of Glyceraldehyde-3-phosphate (G3P) to 1,3-bisphosphoglycerate (BPG) ● (Another) Complex 4 step mechanism ● C1 (red box) is oxidized as NAD+ is reduced to NADH – NADH can provide energy via the electron transport chain (next lecture) Overall Reaction: G3P + NAD+ + Pi ↔ BPG + NADH + H+ ∆G’° = 6.3 kJ/mol Lecture 16 Biochemistry 2000 Slide 13 Enolase Reaction 9: Enolase catalyzes dehydration of 2-phosphoglycerate to the high energy compound, phosphoenolpyruvate (PEP) ● Mg2+ dependent reaction ∆G’° = 7.5 kJ/mol Each of the “special” reactions (aldolase, dehydrogenase, enolase) are unfavorable (have a positive ∆G’°) Lecture 16 Biochemistry 2000 Slide 14 Fates of Pyruvate and NADH Lecture 16 Biochemistry 2000 Slide 15 Metabolic Summary Glycolysis is one of two major metabolic pathways that convert carbohydrates into energy and simpler compounds ● Pentose Phosphate is the other major pathway Pyruvate (under aerobic conditions) enters Citric Acid Cycle ● ● Proteins are broken down to amino acids and enter glycolysis and the citric acid cycle Lipids are broken down to Fatty Acids and glycerol and enter glycolysis and the citric acid cycle Lecture 16 Biochemistry 2000 Slide 16