Glucose Metabolism: Glycolysis and Anaerobic Pathways

• The lecture covers glucose metabolism, specifically glycolysis and anaerobic metabolism.

Structure and Function of Glucose and Glycogen

• Glucose is a monosaccharide.
• Glycogen is a polysaccharide.
• Plasma contains approximately 10 g of glucose.
• Tissues store roughly 400 g of glycogen.
• Glucose is osmotically active.
• Glycogen has low osmolarity.
• Glycolysis is the immediate energy source from glucose.
• Glycogen acts as a medium-term fuel source.
• Glucose is synthesized from non-carbohydrate sources via gluconeogenesis.
• Glycogen is synthesized and broken down.

Glycolysis Key Points

• Definition: Glycolysis converts one molecule of glucose (C6) into two molecules of pyruvate (C3).
• Location: Glycolysis occurs in the cytosol and involves 10 soluble enzymes.
• Function: Glycolysis functions to trap energy via ATP synthesis and also produces intermediates for fat and amino acid synthesis.
• Glycolysis takes place in all tissues within the body.

Glucose Sources for Glycolysis

• Sugars and starch are obtained from the diet.
• Stored glycogen is broken down in the liver.
• Glucose is recycled from lactic acid, amino acids, or glycerol.

Stages of Glycolysis

• Activation involves using up ATP.
• The 6-carbon sugar splits into two halves.
• Oxidation removes 2H atoms.
• ATP is synthesized.

Activation Stages Reactions

• Reaction 1: Glucose to Glucose-6-phosphate using hexokinase.
• Reaction 2: Glucose-6-phosphate to Fructose-6-phosphate using phosphohexose isomerase.
• Reaction 3: Fructose-6-phosphate to Fructose-1,6-bisphosphate using phosphofructokinase.

Important Enzymes in Glycolysis

• Hexokinase: Traps glucose inside the cell.
• Glucokinase: Found in the liver.
• Phosphofructokinase: Key regulatory step in glycolysis.

Hexokinase vs. Glucokinase

• Hexokinase is present in all cells (except liver), has a lower Km, lower Vmax, and is inhibited by Glucose-6-phosphate.
• Glucokinase is present only in the liver, has a higher Km, higher Vmax, and is not inhibited by Glucose-6-phosphate.

Reaction 1: D-Glucose to Glucose 6-Phosphate

• Glucose is trapped in the cell by adding a negatively charged phosphate to it.
• Hexokinase is present in all tissues, excluding the liver.
• Glucokinase is located in the liver.

Reaction 2: Glucose 6-Phosphate to Fructose 6-Phosphate

• It switches from an aldose to ketose sugar.

Reaction 3: Fructose 6-phosphate to Fructose 1,6-bisphosphate

• It is a very important reaction, and a key regulatory step in glycolysis.

Splitting of 6C Sugar to 3C Units

• Fructose 1,6-bisphosphate yields Glyceraldehyde 3-phosphate and Dihydroxyacetone phosphate via aldolase.

Reactions 4 & 5

• Reaction 4 involves Fructose 1,6-bisphosphate being transformed by Aldolase.
• Reaction 5 involves Glyceraldehyde 3-phosphate and Dihydroxyacetone phosphate being transformed by Triose phosphate isomerase.

Oxidation Step

• Glyceraldehyde 3-phosphate is used.
• All reactions occur twice.
• Reaction 6 is a very important reaction.

Reaction 6

• NADH produced will be used in oxidative phosphorylation to generate ATP.
• Not super useful at this stage, but is needed if oxygen is low.

ATP Synthesis Stages

• Reaction 7: 1,3-Bisphosphoglycerate to 3-Phosphoglycerate.
• Reaction 8: 3-Phosphoglycerate to 2-Phosphoglycerate.
• Reaction 9: 2-Phosphoglycerate to Phosphoenolpyruvate.
• Reaction 10: Phosphoenolpyruvate to Pyruvate.

Reaction 7: 1,3-Bisphosphoglycerate to 3-Phosphoglycerate

• ATP is produced via substrate-level phosphorylation.
• Two molecules of ATP are produced in this step because you do each reaction twice.

Reaction 8: 3-Phosphoglycerate to 2-Phosphoglycerate

• It is only an isomerisation reaction.

Reaction 9

• PEP will appear again when anaplerotic filling of the TCA cycle and gluconeogenesis are covered.

Reaction 10

• Is an irreversible reaction, during this reaction ATP is produced via substrate level phosphorylation.

Glycolysis Yields Summary

• Early stages use 2 ATP.
• Later stages make 4 ATP.
• Net yield is 2 ATP.

Anaerobic Glycolysis

• Pyruvate is not metabolized to CO2, when oxygen supplies to tissues are limited.
• Pyruvate is converted to lactate in order to convert the cofactor NADH back to NAD+.

Lactate Dehydrogenase Reaction

• It is a reversible reaction that consumes NADH when converting pyruvate to lactate
• This reaction occurs in the liver and muscle tissue.

Metabolic Fates of Pyruvate

• Pyruvate can become Lactate when there is no O2, or no mitochondria.
• Pyruvate can become Acetyl CoA when O2 is there.
• Pyruvate can become Ethanol when micro organisms are only present.
• Acetyl CoA can become Citric Acid Cycle
• Citric acid can become C02 when there is O2 present.
• Ethanol can become Fatty Acids intake with excess calories

Glycolysis Regulation

• Includes allosteric control and hormonal control.

Feedback Inhibition of Glycolysis

• Think about the cell's needs at any moment; If there is plenty of energy, does it need glycolysis or energy storage?

Specialised functions in Tissues

• Skeletal muscle: ATP production during intense exercise.
• Red blood cells: Only pathway for ATP production in RBC.
• Brain: Major source of ATP

Summary of glycolysis

• Main catabolic pathway for glucose, present in all tissues.
• Only energy yielding pathway that can function either in aerobic or anaerobic conditions.
• Energy yields are low (2 ATP).
• Pathway produces intermediates fro fats etc.

Discoveries and Dilemmas

• These are extras to think about.

Warburg Effect

• Tumour cells preferentially generate energy through anaerobic glycolysis.
• Tumours produce lactate at up to 200x the rate of ‘healthy’ cells, even when mitochondria are intact.

Explore glucose and glycogen structure, highlighting their functions in energy storage and metabolism. Glycolysis, the process of converting glucose to pyruvate, occurs in the cytosol and involves 10 soluble enzymes. Learn about ATP synthesis and the role of glycolysis in fat and amino acid production.