Glycolysis: Steps and Energy Yield

• Glycolysis is module LCS 105, for year 1, semester 2, academic year 2024-2025
• The objectives are to illustrate glycolysis steps, calculate the energy yield from the glycolytic pathway, and explain the biochemical importance
• Anabolism consists of synthesis of macromolecules from simple ones, and is required for tissue growth and maintenance
• Catabolism consists of the breakdown of large molecules into smaller ones

Fate of Absorbed Glucose

• Glucose is either, taken up by different tissues and utilized, sotred in excess, or excreted in urine

Utilization by the Tissues

• Oxidation is a utilization method to produce energy
• Major pathways are glycolysis and Krebs cycle
• Minor pathways are hexose monophosphate and uronic acid pathways
• Conversion to other substances include Ribose and deoxyribose (for the structure of RNA and DNA)
• Galactose in lactose of milk and glycolipids and Fructose in semen
• Glycerol-3 P is for formation of triacylglycerols
• Non-essential amino acids enter in formation of proteins

Glycolysis

• A major pathway for Glucose utilization and is also known as the Embden – Meyerhof pathway
• Glycolysis is unique and can function either aerobically or anaerobically, depending on the availability of oxygen and intact mitochondria
• Glycolysis occurs in the cytoplasm of all body cells and tissues
• Glycolysis breaks down glucose to provide energy (in the form of ATP) and intermediates for other metabolic pathways

Reactions of Glycolysis

• Phase 1 (Energy investment phase) activates glucose and cleaves it into 2 trioses
• Phase 2 (Payoff Phase) involves the oxidation of 2 trioses which gives pyruvate or lactate at the end

Energy investment phase step 1: Hexokinase

• Glucose is phosphorylated to trap it inside the cell
• The negative phosphate group and the negative charge of the cell membrane result in repulsion

Energy investment phase step 2: Phosphoglucose Isomerase

• Converts Glucose-6-P into Fructose 6-P

Energy investment phase step 3: Phospho-fructokinase-1 (PFK I)

• Converts Fructose 6-P into Fructose 1,6 - bisphosphate

Energy investment phase step 4: Aldolase A

• Transforms Fructose 1,6-bisphosphate

Energy investment phase step 5: Triose phosphate-Isomerase

• Transforms Glyceraldehyde 3-phosphate into Dihydroxyacetone phosphate

Payoff Phase step 1: G3P Dehydrogenase

• Begins the payoff phase in glycolysis

Payoff Phase step 2: Phospho glycerate kinase

• Results in 1.3 bisphosphoglycerate

Payoff Phase step 3: Phosphoglycerate Mutase

• Results in 3-Phosphoglycerate

Payoff Phase step 4: Enolase

• Transforms 2-Phosphoglycerate into Phosphoenolpyruvate

Payoff Phase step 5: Pyruvate Kinase

• Results in Phosphoenol pyruvate

Summary of Glycolysis

• Glucose leads to, 2 (Glyceraldehyde-3-P) which produces 2(1,3 bisphosphoglycerate), which leads to 2(3-Phosphoglycerate) and 2(2-Phosphoglycerate)
• Finally 2(Phosphoenol pyruvate) produces 2 Pyruvate and under anaerobic conditions produces 2 Lactate

Outcome of Glycolysis

• Through Glycolysis Glucose generates 2 ATP
• Through glycolysis 2NADH gets transferred to the ETC for energy extraction
• Then glycolysis generates 2 Pyruvate to go to the next stage

Net Energy Gain

• Net energy gain of aerobic glycolysis is 8 ATP
• 2 X 2 ATP - 2 ATP (Of activation) = 2 ATP
• 2 NADH → ETC (2X3) = 6 ATP

End Products

• The end products of glycolysis are 2 ATP, 2 pyruvate, and 2 NADH+H
• 2 Pyruvate enter Kreb's Cycle
• 2 NADH+H go to the Respiratory Chain in the mitochondria, and To give 6 ATP

Anaerobic Glycolysis

• Net energy gain of Anaerobic glycolysis is 2 ATP only
• 2X 2 ATP in glycolysis = 4
• 4 - 2 (ATP of activation) = 2 ATP only

Limitation

• Glycolysis releases only a small fraction of the energy contained in the glucose molecule
• It is a valuable source of energy under several conditions, such as No Mitochondria or during Hypoxia

Biological Importance

• Glycolysis leads to Energy production in both aerobic and anaerobic conditions
• In anaerobic conditions, it serves as the only energy source for anaerobic tissues
• Under aerobic conditions, it acts as a preparatory pathway for complete glucose oxidation by the TCA cycle
• Glycolysis leads to Synthetic functaions where intermediates of glycolysis have synthetic function
• 3 phosphoglycerate can form serine
• Dihydroxy acetone provides glycerol – 3 – for triacylglycerol synthesis in adipose tissue

Summary

• Glycolysis is the major oxidative pathway for glucose
• Glycolysis is employed by all tissues
• Glycolysis is a tightly-regulated pathway
• PFK-1 is the rate-limiting regulatory enzyme
• Glycolysis is mainly a catabolic pathway for ATP production, But It has some anabolic features
• Glycolysis is responsible for the synthesis of triacylglycerol from dihydroxyacetone phosphate, the synthesis of 2,3 BPG, and the synthesis of alanine from pyruvate

Additional Summary points

• Pyruvate kinase deficiency in RBCs results in hemolytic anemia
• Aerobic glycolysis produces 8 ATP
• Anaerobic glycolysis produces 2 ATP
• Glycolysis in RBCs without 2,3 BPG synthesis produces 2 ATP
• Glycolysis in RBCs with 2,3 BPG synthesis produces 0 ATP
• A 3-year-old girl with jaundice and splenomegaly was found to have a pyruvate kinase deficiency based on low PK activity (3.7 U/g Hb)
• Pyruvate kinase deficiency can be treated by blood transfusion and splenectomy