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Glycolysis PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "GLYCOLYSIS".

This medical PowerPoint presentation talks about glycolysis, a metabolic pathway that occurs in the cytoplasm of cells and is the first step in both aerobic and anaerobic respiration. It involves the breakdown of glucose into two pyruvate molecules, which can then be further metabolized to produce ATP (adenosine triphosphate) - the primary energy currency of cells.

The process of glycolysis can be broken down into 10 steps, each of which is catalyzed by a specific enzyme. The overall reaction of glycolysis is as follows:

Glucose + 2 NAD+ + 2 ADP + 2 Pi ? 2 pyruvate + 2 NADH + 2 ATP + 2 H+

Here, glucose is the starting substrate, NAD+ is a coenzyme that accepts electrons during the reaction, ADP and Pi (inorganic phosphate) are used to produce ATP, pyruvate is the end product, and NADH is the reduced form of NAD+.

Tags : glycolysis, metabolic pathway, endocrinology, endocrinology PowerPoint presentation

Published on : Apr 18, 2023 | Views : 830 | Downloads : 2

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Slide 1-

GLYCOLYSIS Learning objectives: List the enzymes and intermediates involved in glycolysis List the irreversible and regulated steps of glycolysis Discuss regulation of glycolysis
Slide 2-

Glucose transporters Name Tissue location Km . GLUT1 All mammalian tissues 1 mM Basal glucose uptake GLUT2 Liver and pancreatic β cells 15-20 mM Uptake approximately proportional to glucose conc. GLUT3 All mammalian tissues 1 mM Basal glucose uptake GLUT4 Skeletal muscle and fat 5 mM Recruited to cell membrane in insulin dependent manner Blood glucose concentrations Normal plasma glucose concentrations roughly 3.9 – 8.3 mM
Slide 3-

Glucose transporters
Slide 4-

GLUT4 is recruited to cell membrane by insulin-dependent translocation The increase in number of GLUT4 transporters in the cell membrane increases the speed of glucose transport. Insulin stimulates glucose uptake in fat tissue and skeletal muscle
Slide 5-

Glycolysis Stoichiometry 1 Glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 Pyruvate + 2 ATP + 2 H2O + 2 NADH + 2 H+ (Emden-Meyerhof glycolytic pathway) Aerobic conditions: Oxygen is required to re-oxidize NADH to NAD+ via the electron transport chain Anaerobic conditions: NADH is re-oxidized to NAD+ in a reaction in which pyruvate is reduced to lactate (humans) or ethanol (yeast and other microorganisms) Glycolysis is used to provide energy (in the form of ATP) and intermediates for other metabolic pathways. Glycolysis occurs in the cytoplasm.
Slide 6-

C6H12O6 O O- C C O CH3 Pyruvate Glucose O O- C HO C H CH3 Lactate H HO C H CH3 Ethanol CO2 + H2O + O2 GLYCOLYSIS FERMENTATION TCA CYCLE & OXIDATIVE PHOSPHORYLATION
Slide 7-

O H C H- C - OH CH2OH CH2OH C O CH2OH CH2OH H- C - OH CH2OH O OH C H- C - OH CH2OH Glycerol Glyceraldehyde Glyceric acid Glycerate O O- C H- C - OH CH2OH O O- C C O CH3 Dihydroxyacetone Pyruvate (α-keto carboxylic acid)
Slide 8-

Glucokinase Hexokinase R kinase R-OH + ATP R-OPO32- + ADP Irreversible Highly exergonic (ΔG = -33.5 kJ/mol) Regulated step in glycolysis Glucose + ATP Glucose 6-phosphate + ADP
Slide 9-

Normal physiological range Glucokinase is a glucose sensor
Slide 10-

Ca Glucose GK G-6-P Pyruvate ATP ADP K + Depolarization 2+ Ca 2+ Insulin GLUT2 Glucose-stimulated insulin secretion in pancreatic beta cells Glucose metabolism determines secretion of insulin
Slide 11-

GLUT2 is a high Km, high efficiency glucose transporter (not rate-limiting) Glucokinase has a high Km (is rate-limiting) - reaction velocity is roughly proportional to glucose concentration - therefore glucose metabolism and insulin secretion in beta cells is roughly proportional to glucose concentration
Slide 12-

Phosphoglucose isomerase Glucose 6-phosphate Fructose 6-phosphate
Slide 13-

Irreversible Highly exergonic (ΔG = -22.2 kJ/mol) Regulated step in glycolysis The main regulatory enzyme of the glycolytic pathway ATP balance: 2 ATP spent in phosphorylating glucose and fructose 6-phosphate Fructose 6-phosphate + ATP Fructose 1,6-bisphosphate + ADP Phosphofructokinase
Slide 14-

CH2OPO32- Ι C = O Ι HO – C – H Ι H – C – OH Ι H – C – OH Ι CH2OPO32- Fructose 1,6-bisphosphate CH2OPO32- Ι C = O + Ι CH2OH Dihydroxyacetone phosphate CHO Ι H – C – OH Ι CH2OPO32- Glyceraldehyde 3-phosphate Aldolase
Slide 15-

CH2OPO32- Ι C = O Ι CH2OH Dihydroxyacetone phosphate CHO Ι H – C – OH Ι CH2OPO32- Glyceraldehyde 3-phosphate Triose phosphate isomerase
Slide 16-

Mixed anhydride of phosphoric acid and a carboxylic acid High energy bond Energy from oxidation of glyceraldehyde 3-phosphate to the carboxylic acid is “captured” in the formation of the acyl~phosphate linkage CHO Ι H – C – OH Ι CH2OPO32- Glyceraldehyde 3-phosphate C Ι H – C – OH Ι CH2OPO32- 1,3-Bisphosphoglycerate 2-O3PO O + NAD+ + Pi + NADH + H+ Glyceraldehyde 3-phosphate dehydrogenase
Slide 17-

Substrate-level phosphorylation ATP balance: 2 ATP spent in phosphorylating glucose and fructose 6-phosphate 2 x 1 ATP generated in the phosphoglycerate kinase step 1,3-Bisphosphoglycerate + ADP 3-Phosphoglycerate + ATP Phosphoglycerate kinase
Slide 18-

3-Phosphoglycerate 2-Phosphoglycerate 2-Phosphoglycerate Phosphoenolpyruvate + H2O Phosphoglycerate mutase Enolase
Slide 19-

Substrate-level phosphorylation Irreversible Highly exergonic (ΔG = -16.7 kJ/mol) Regulated step in glycolysis Phosphoenolpyruvate + ADP Pyruvate + ATP Pyruvate kinase
Slide 20-

ATP balance: 2 ATP spent in phosphorylating glucose and fructose 6-phosphate 2 x 1 ATP generated in the phosphoglycerate kinase step 2 x 1 ATP generated in the pyruvate kinase step 2 molecules of ATP are generated from 1 molecule of glucose in glycolysis Phosphoenolpyruvate + ADP Pyruvate + ATP Pyruvate kinase
Slide 21-

Stoichiometry 1 Glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 Pyruvate + 2 ATP + 2 H2O + 2 NADH + 2 H+ The 3 Irreversible Enzyme-catalyzed Reactions Hexokinase (or glucokinase) Phosphofructokinase Pyruvate kinase
Slide 22-

In yeast and many other microorganisms: Pyruvate + H+ Acetaldehyde + CO2 Acetaldehyde + NADH + H+ Ethanol + NAD+ Pyruvate decarboxylase Alcohol dehydrogenase
Slide 23-

In mammals: Under anaerobic conditions, e.g. in rapidly contracting muscle In erythrocytes Under aerobic conditions NADH + H+ + ½ O2 NAD+ + H2O Electron transport chain Pyruvate + NADH + H+ Lactate + NAD+ Lactate dehydrogenase
Slide 24-

Fates of pyruvate generated by glycolysis Pyruvate Acetyl CoA Oxaloacetate Alanine Oxidation via TCA cycle Fatty acid synthesis Lactate PEP
Slide 25-

Regulation of metabolic pathways The flow of intermediates through metabolic pathways is controlled by four mechanisms Substrate availability Allosteric activation or inhibition Covalent modification of enzymes Induction/repression of enzyme synthesis
Slide 26-

Signals Energy state ATP high-energy signal ADP, AMP low-energy signal Availability of biosynthetic intermediates Citrate Alanine Metabolic state of the whole organism Insulin – signal of the fed state High blood glucose – signal of the fed state Glucagon – signal of the fasted state Epinephrine – signal of stress Metabolic regulation of biochemical pathways makes “physiological sense” Control of flow though a pathway is often distributed among several enzymatic steps in the pathway
Slide 27-

Fed state Fasted state glucose P GK glucose glucose-6-phosphate GLUT 2 Insulin receptor Insulin Lipids Pyruvate Hepatic glucose uptake and utilization Hepatic glucose production glucose P glucose glucose-6-phosphate GLUT 2 Receptor Glucagon Glycogen Gluconeogenesis G6Pase Liver cell - Hepatocyte Glycolysis Glycolysis Glycogen
Slide 28-

Rapidly contracting state Resting state glucose P Hexokinase glucose glucose-6-phosphate GLUT 4 glucose P glucose glucose-6-phosphate GLUT 4 Glycogen Skeletal muscle cell Glycogen Low ATP High AMP ATP Glycolysis Glycolysis High ATP Low AMP ATP
Slide 29-

Hexokinase Glucose 6-phosphate (low phosphofructokinase activity) Glucokinase High blood glucose (release from GKRP, High Km) Insulin stimulates gene transcription (only in liver) - + + Glucokinase Hexokinase Glucose + ATP Glucose 6-phosphate + ADP
Slide 30-

Glucokinase (GK) can be bound to the Glucokinase Regulatory Protein (GKRP). When GK is bound to the GKRP, it is sequestered in the nucleus and is inactive. Glucose promotes dissociation of GK from the GKRP, allowing GK to be transported to the cytoplasm where it is active in glycolysis.
Slide 31-

The main regulatory step of glycolysis - + + ATP (high-energy state) Citrate (abundance of biosynthetic building blocks) H+ (build-up of lactate) AMP (low-energy state) Fructose 2,6-bisphosphate (fed state, high insulin/glucagon ratio) - - Fructose 6-phosphate + ATP Fructose 1,6-bisphosphate + ADP Phosphofructokinase
Slide 32-

ATP is a substrate for phosphofructokinase ATP can also bind to an allosteric site Fructose 6-phosphate + ATP Fructose 1,6-bisphosphate + ADP Phosphofructokinase
Slide 33-

- + + - - ATP (high-energy state) Alanine (abundance of alanine which is synthesized from pyruvate and is an important gluconeogenic substrate) Glucagon (fasted state) Fructose 1,6-bisphosphate (feed-forward mechanism) Glucose (stimulates gene transcription) Phosphoenolpyruvate + ADP Pyruvate + ATP Pyruvate kinase
Slide 34-

Occurs in liver in the fasted state Glucagon binding to the glucagon receptor  Activation of adenylyl cyclase  Increase in [cAMP]  Activation of protein kinase A  Phosphorylation and inactivation of pyruvate kinase