Glycolysis and Gluconeogenesis Chapter 14 Page 521 534
- Slides: 40
Glycolysis and Gluconeogenesis Chapter 14 (Page 521 -534, 543 -550, 554) 1
1. Central Importance of Glucose • Glucose is an excellent fuel – Yields good amount of energy upon oxidation – Can be efficiently stored in the polymeric form – Many organisms and tissues can meet their energy needs on glucose only • Glucose is a versatile biochemical precursor – Bacteria can use glucose to build the carbon skeletons of: • All the amino acids • Membrane lipids • Nucleotides in DNA and RNA • Cofactors needed for the metabolism
2. Four Major Pathways of Glucose Utilization • Storage – Can be stored in the polymeric form (starch, glycogen) – When there’s plenty of excess energy • Synthesis of Structural Polysaccharides – For example, in cell walls of bacteria, fungi, and plants – Extracellular matrix • Glycolysis – Generates energy via oxidation of glucose – Short-term energy needs • Pentose Phosphate Pathway – Generates NADPH via oxidation of glucose – For detoxification and the biosynthesis of lipids and nucleotides
2. Four Major Pathways of Glucose Utilization
3. Overview of Glycolysis and Gluconeogenesis Glucose Glycolysis Gluconeogensis
Glycolysis 6
1. Glycolysis: Overview • In the evolution of life, glycolysis probably was one of the earliest energy-yielding pathways. • It developed before photosynthesis, when the atmosphere was still anaerobic. • Thus, the task upon early organisms was: How to extract free energy from glucose anaerobically? • The solution: – First: Activate it by phosphorylation – Second: Collect energy from the high-energy metabolites
1. Glycolysis: Overview • The chemistry of this reaction sequence has been completely conserved. – The glycolytic enzymes of vertebrates are closely similar in AA sequence and 3 -D structure to their homologs in yeast and spinach. • Glycolysis differs among species only in the details of its regulation and in the subsequent metabolic fate of the pyruvate formed.
1. Glycolysis: Overview We will be focusing on aerobic glycolysis, which involves: A. Cytosolic enzymes (soluble) B. Substrate-level phosphorylation § Involves soluble enzymes and chemical intermediates
2. Glycolysis: Importance • Sequence of enzyme-catalyzed reactions by which glucose is converted into pyruvate • Pyruvate can be further aerobically oxidized • Pyruvate can be used as a precursor in biosynthesis • Some of the free energy from oxidation is captured by the synthesis of ATP and NADH • Research of glycolysis played a large role in the development of modern biochemistry – Understanding the role of coenzymes – Discovery of the pivotal role of ATP – Development of methods for enzyme purification
3. Feeder Pathways for Glycolysis
3. Feeder Pathways for Glycolysis • Glucose molecules are cleaved from glycogen and starch by glycogen phosphorylase – Yielding glucose-1 -phosphate • Disaccharides are hydrolyzed – Lactose: glucose and galactose – Sucrose: glucose and fructose • Fructose, galactose, and mannose enter glycolysis at different points
4. Glycolysis: Overview
4 A. Glycolysis: The Preparatory Phase • Kinase: Enzyme that catalyzes the phosphorylation of certain molecules by ATP. • For each glucose, two molecules of glyceraldehyde-3 phosphate are formed. • Two ATP are consumed.
4 B. Glycolysis: The Payoff Phase • Dehydrogenase: Enzyme that catalyzes the removal of pairs of hydrogen atoms from their substrates. • NAD+ (Nicotinamide adenine dinucleotide)
4 B. Glycolysis: The Payoff Phase • Each phosphoryl (P) has two negative charges (PO 32 -). • Four ATP are formed. • Two molecules of pyruvate are produced.
Step 1: Phosphorylation of Glucose • The terminal phosphorus undergoes nucleophilic attack by the highlighted OH group of glucose. - ATP appears as Mg. ATP to shield the negative charge.
Step 1: Phosphorylation of Glucose • Rationale – Traps glucose inside the cell because there are no transporters that facilitate export of phosphorylated glucose out of the cell – Lowers intracellular glucose concentration to allow further uptake • This process uses the energy of ATP
Step 1: Phosphorylation of Glucose • Nucleophilic oxygen at C 6 of glucose attacks the last ( ) phosphate of ATP • ATP-bound Mg 2+ facilitates this process by shielding the negative charges on ATP • Highly thermodynamically favorable/irreversible – Regulated mainly by substrate inhibition
Step 2: Phosphohexose Isomerization
Step 2: Phosphohexose Isomerization • Rationale – C 1 of fructose is easier to phosphorylate by PFK – Allows for symmetrical cleave by aldolase • An aldose (glucose) can isomerize into a ketose (fructose) via an enediol intermediate • The isomerization is catalyzed by the active-site glutamate, via general acid/base catalysis • Slightly thermodynamically unfavorable/reversible – Product concentration kept low to drive forward ΔG = ΔG’° + RT ln [P]/[S]
Mechanism of Phosphohexose Isomerase
Step 3: 2 nd Priming Phosphorylation
Step 3: 2 nd Priming Phosphorylation • Rationale – Further activation of glucose – Allows for 1 phosphate/3 -carbon sugar after step 4 • First Committed Step of Glycolysis – Fructose 1, 6 -bisphosphate is committed to become pyruvate and yield energy • This process uses the energy of ATP • Highly thermodynamically favorable/irreversible
Step 4: Aldol Cleavage of F-1, 6 -b. P
Step 4: Aldol Cleavage of F-1, 6 -b. P • Rationale – Cleavage of a six-carbon sugar into two three-carbon sugars – High-energy phosphate sugars are three-carbon sugars • Animal and plant aldolases employ covalent catalysis • Thermodynamically unfavorable/reversible – GAP concentration kept low to pull reaction forward
Mechanism of Class I Aldolases: Covalent Catalysis
Mechanism of Class I Aldolases: Base Catalysis
Mechanism of Class I Aldolases: Base Catalysis
Mechanism of Class I Aldolases: Acid Catalysis
Mechanism of Class I Aldolases: Release of Product
Step 5: Triose Phosphate Interconversion
Glucose Carbons in GAP
Step 5: Triose Phosphate Interconversion • Rationale: – Allows glycolysis to proceed by one pathway – Completes preparatory phase • Aldolase creates two triose phosphates: – – Dihydroxyacetone Phosphate (DHAP) Glyceraldehyde-3 -Phosphate (GAP) Only GAP is the substrate for the next enzyme DHAP must be converted to GAP • Thermodynamically unfavorable/reversible – GAP concentration kept low to pull reaction forward
Step 6: Oxidation of GAP
Step 6: Oxidation of GAP +1 NAD+ + H+ + 2 e- → NADH +3
Step 6: Oxidation of GAP • Rationale: – Generation of a high-energy phosphate compound – Incorporates inorganic phosphate – Which allows for net production of ATP • Oxidation of aldehyde with NAD+ gives NADH • Active site cysteine – Forms high-energy thioester intermediate – Subject to inactivation by oxidative stress • Thermodynamically unfavorable/reversible – Coupled to next reaction to pull forward
Mechanism of GAPDH
Step 7: 1 st Production of ATP
Step 7: 1 st Production of ATP • Rationale: – Substrate-level phosphorylation to make ATP • 1, 3 -bisphoglycerate is a high-energy compound – Can donate the phosphate group to ADP to make ATP • Kinases are enzymes that transfer phosphate groups from ATP to various substrates • Highly thermodynamically favorable/reversible – Is reversible because of coupling to GAPDH reaction
- Regulation of glycolysis and gluconeogenesis
- Glucogen metabolism
- Ntp 534
- Texas transportation code 521
- Cis 521
- Cse 521
- Zemax thermal analysis
- Ley 24 521
- Optisystem tutorial
- Glycolysis
- Glycogenolysis and gluconeogenesis
- Amp glycolysis
- Krebes cycle
- Apa cover pafe
- Precursores de gluconeogenesis
- Glucogenesis vs gluconeogenesis
- Gluconeogenesis sustrato y producto
- Glycogen metabolism
- Gluconeogenesis purpose
- Hexokinase phosphofructokinase and pyruvate kinase
- Precursor of gluconeogenesis
- Gluconeognesis
- Pep carboxykinase
- Precursores de gluconeogenesis
- Gluconeogenesis definition
- What are the substrates for gluconeogenesis
- Glycolysis overall reaction
- Net reaction of gluconeogenesis
- Gluconeogenesis from lactate
- Gluconeogenesis from lactate
- Glukoneogenez
- Piruvato
- Glucose 6 phosphatase
- Pirüvat karboksilaz koenzimi
- Glucose neogenesis
- Pyruvate carboxylase gluconeogenesis
- Insulin and glycolysis
- Insulin and glycolysis
- Krebs cycle inputs
- Input of krebs cycle
- Nelson biology 20 answer key