Chapter 16: (PPT) Glycolysis and Gluconeogenesis Notes

Overview of Glycolysis and Gluconeogenesis

• Glycolysis: Metabolic pathway converting glucose into pyruvate, producing ATP without oxygen (anaerobic).

• Gluconeogenesis: Synthesis of glucose from non-carbohydrate sources, crucial during fasting.

Glycolysis: The Energy-Conversion Pathway

• Glycolysis consists of a sequence of reactions that:

  • Metabolizes one glucose molecule into two pyruvate molecules.

  • Produces a net yield of two ATP.

  • Exists in both prokaryotic and eukaryotic cells.

Anaerobic Processing of Glucose

• Lactic Acid Fermentation: Produces lactate in absence of oxygen.

• Alcoholic Fermentation: Converts glucose to ethanol in yeast.

• Complete Oxidation: When oxygen is available, glucose is fully oxidized to CO2 and H2O, leading to more energy production.

Formation and Transport of Glucose from Carbohydrates

• Dietary carbohydrates (starch, glycogen) broken down by:

  • α-amylase: Pancreatic enzyme that breaks down starch.

  • α-glucosidase: Hydrolyzes maltose and related compounds into glucose in the intestine.

  • Sucrase: Converts sucrose to glucose and fructose.

• Transport of Monosaccharides: Monosaccharides (like glucose) enter intestinal cells via active transport, then into the bloodstream via glucose transporters (GLUT1-5), which utilize a 12-transmembrane-helix structure.

Stages of Glycolysis

• Stage 1: Traps and modifies glucose without ATP production:

  1. Glucose is phosphorylated to glucose 6-phosphate (G-6P) by Hexokinase.

  2. G-6P is then converted to fructose 6-phosphate (F-6P) by Phosphoglucose isomerase.

  3. F-6P is phosphorylated to fructose 1,6-bisphosphate (F-1,6-BP) by Phosphofructokinase. This reaction is rate-limiting and allosterically regulated.

  4. Cleavage of F-1,6-BP to yield glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP).

  5. DHAP is isomerized to GAP via Triose phosphate isomerase (TPI).

• Stage 2: Oxidation of GAP to pyruvate, generating ATP:

  1. GAP is converted to 1,3-bisphosphoglycerate (1,3-BPG) by Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), yielding NADH.

  2. Transfer of phosphate from 1,3-BPG to ADP forms ATP via Phosphoglycerate kinase.

  3. Series of reactions convert 3-phosphoglycerate through multiple intermediates to form pyruvate, generating a second ATP.

Regulation of Glycolysis

• Glycolysis is tightly regulated through irreversible enzymes:

  1. Hexokinase: Inhibited by its product G-6P.

  2. Phosphofructokinase (PFK): Key regulatory step in glycolysis; inhibited by ATP, activated by AMP.

  3. Pyruvate kinase: Inhibited by ATP and alanine; activated by fructose 1,6-bisphosphate.

Pyruvate's Fate After Glycolysis

• Under Aerobic Conditions: Pyruvate is converted to acetyl-CoA for entry into the citric acid cycle.

• Under Anaerobic Conditions: Converted to lactate via lactic acid fermentation or ethanol via alcoholic fermentation.

Gluconeogenesis Pathway

• Gluconeogenesis converts pyruvate into glucose, primarily in the liver. It is not a direct reversal of glycolysis due to the need to bypass three irreversible steps of glycolysis:

  1. Conversion of pyruvate to phosphoenolpyruvate via pyruvate carboxylase (requires ATP) and phosphoenolpyruvate carboxykinase.

  2. Conversion of fructose 1,6-bisphosphate to fructose 6-phosphate via fructose 1,6-bisphosphatase (key regulatory step).

  3. Final conversion of glucose 6-phosphate to glucose by glucose 6-phosphatase in the ER of liver cells.

• Key Precursors: Lactate, amino acids, and glycerol can enter gluconeogenesis at various points.

Regulation of Gluconeogenesis

• Reciprocal regulation with glycolysis to ensure proper metabolic control based on energy availability.

• Hormonal control (insulin and glucagon) determines the activity of glycolysis and gluconeogenesis based on blood glucose levels.

REVIEW GUIDE:

** = already added to Anki slides

• Define glycolysis versus gluconeogenesis **

• How are foods/sugars broken down to glucose to use for glycolysis? **

• Recognize how monosaccharides are transported from the intestine to the blood stream and then to other organs; GLUT transporters- how do they work in general to move glucose into cells (do NOT have match which GLUT transporter is present in each organ on slide 7)

• For the glycolytic pathway, you will have to know the various names of the substrates for each part of the reaction process and the enzymes associated with each step.

  • You should know what the various substrates look like, but you can skip intermediate structures. Know where NAD is converted to NADH and where ATP is hydrolyzed or created.

• Converting glucose to glucose-6-phsophate keeps the glucose in the cell

  • I will not ask details on the catalytic mechanism of triose phosphate isomerase (slides 18 and 19) or GADPH (slides 25 and 26)

• You will not be asked about specific values for DG’s

• Know the net scorecard for glycolysis (slide 32)

• NADH and the need to regenerate NAD+ leads to fermentation if no oxygen involved; know ethanol and lactate fermentation steps and enzymes, net molecules generated (slides 37 and 40)

• How do other sugars like galactose and fructose enter glycolytic pathway? (Skip excess fructose slide 46)

• Skip lactose intolerance slide 50

• What regulates the glycolytic pathway? (See slide 51 to start, then the subsequent slides show how this works in muscle and liver)

• Gluconeogenesis- what is it? What are the major precursors? Where do those precursors enter the pathway? (Slide 69 but don’t memorize the whole thing! Just where glycerol, amino acids and lactate enter)

• How is pyruvate converted to oxaloacetate? (Know Slide 71 but skip the details in slides 72-74)

• Once oxaloacetate is formed in the mitochondria, how does it get out to the cytoplasm? (Slide 76) Skip slides 77-79

• Free glucose as a control point- why? Slide 80

• Reciprocal regulation of glycolysis and gluconeogenesis- note slide 85

• Skip slide 86

• What is the Cori cycle? Slide 88

• Skip slide 89- too much!

REVIEW GUIDE ANSWERS

Overview of Glycolysis and Gluconeogenesis

• Glycolysis: Metabolic pathway converting glucose into pyruvate, producing ATP without oxygen (anaerobic).

• Gluconeogenesis: Synthesis of glucose from non-carbohydrate sources, crucial during fasting.

Glycolysis: The Energy-Conversion Pathway

• Glycolysis consists of a sequence of reactions that:

  • Metabolizes one glucose molecule into two pyruvate molecules.

  • Produces a net yield of two ATP.

  • Exists in both prokaryotic and eukaryotic cells.

Formation and Transport of Glucose from Carbohydrates

• Dietary carbohydrates (starch, glycogen) are broken down by:

  • α-amylase: Pancreatic enzyme that breaks down starch.

  • α-glucosidase: Hydrolyzes maltose and related compounds into glucose in the intestine.

  • Sucrase: Converts sucrose to glucose and fructose.

• Transport of Monosaccharides: Monosaccharides (like glucose) enter intestinal cells via active transport, then into the bloodstream via glucose transporters (GLUT1-5), which utilize a 12-transmembrane-helix structure.

Stages of Glycolysis

• Stage 1: Traps and modifies glucose without ATP production:

  1. Glucose is phosphorylated to glucose 6-phosphate (G-6P) by Hexokinase.

  2. G-6P is converted to fructose 6-phosphate (F-6P) by Phosphoglucose isomerase.

  3. F-6P is phosphorylated to fructose 1,6-bisphosphate (F-1,6-BP) by Phosphofructokinase, a rate-limiting enzyme.

  4. Cleavage of F-1,6-BP yields glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP).

  5. DHAP is isomerized to GAP via Triose phosphate isomerase (TPI).

• Stage 2: Oxidation of GAP to pyruvate, generating ATP:

  1. GAP is converted to 1,3-bisphosphoglycerate (1,3-BPG) by Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), yielding NADH.

  2. Transfer of phosphate from 1,3-BPG to ADP forms ATP via Phosphoglycerate kinase.

  3. Glycerate is converted to pyruvate, generating a second ATP.

Regulation of Glycolysis

• Glycolysis is regulated through irreversible enzymes:

  1. Hexokinase is inhibited by G-6P.

  2. Phosphofructokinase (PFK): Key regulatory step; inhibited by ATP, activated by AMP.

  3. Pyruvate kinase: Inhibited by ATP and alanine; activated by fructose 1,6-bisphosphate.

Pyruvate's Fate After Glycolysis

• Under Aerobic Conditions: Converted to acetyl-CoA for the citric acid cycle.

• Under Anaerobic Conditions: Converted to lactate via lactic acid fermentation or ethanol via alcoholic fermentation, leading to regeneration of NAD+.

Gluconeogenesis Pathway

• Gluconeogenesis converts pyruvate into glucose, primarily in the liver. It bypasses three irreversible steps of glycolysis:

  1. Pyruvate is converted to phosphoenolpyruvate via pyruvate carboxylase (requires ATP) and phosphoenolpyruvate carboxykinase.

  2. Fructose 1,6-bisphosphate is converted to fructose 6-phosphate via fructose 1,6-bisphosphatase.

  3. Glucose 6-phosphate is converted to glucose by glucose 6-phosphatase in liver ER.

• Key Precursors: Lactate, amino acids, and glycerol can enter gluconeogenesis at various points.

Conversion of Oxaloacetate

• Once oxaloacetate is formed in the mitochondria, it is transported out to the cytoplasm.

Reciprocal Regulation of Glycolysis and Gluconeogenesis

• There is reciprocal regulation of the two pathways to maintain metabolic control based on energy needs and availability. Insulin and glucagon play significant roles in this regulation.

The Cori Cycle

• The Cori cycle describes the metabolic pathway involving the conversion of lactate back to glucose, allowing for continuous supply of energy, especially during anaerobic conditions.

• Glycolysis:

  • Converts glucose into pyruvate.

  • Produces energy (ATP) anaerobically.

  • Occurs in both prokaryotic and eukaryotic cells.

  • Involves a series of ten enzyme-catalyzed reactions.

  • Key regulatory enzymes: Hexokinase, Phosphofructokinase (PFK), Pyruvate kinase.

  • Yield: Net production of two ATP molecules per glucose.

• Gluconeogenesis:

  • Synthesizes glucose from non-carbohydrate sources (like lactate and amino acids).

  • Consumes energy (ATP) to produce glucose.

  • Primarily occurs in the liver.

  • Bypasses three irreversible steps of glycolysis.

  • Key regulatory enzyme: Fructose 1,6-bisphosphatase.

  • Glucose produced is essential during fasting periods.

Question: Describe the process through which dietary carbohydrates (starch, glycogen) are broken down into glucose for glycolysis. Include the enzymes involved and their specific functions. Answer: Dietary carbohydrates are broken down by: - α-amylase: A pancreatic enzyme that breaks down starch into simpler sugars. - α-glucosidase: Hydrolyzes maltose and related compounds into glucose in the intestine. - Sucrase: Converts sucrose into glucose and fructose. Once converted to monosaccharides, glucose enters intestinal cells via active transport and then into the bloodstream via glucose transporters (GLUT1-5).

What is the primary enzyme responsible for breaking down starch into simpler sugars during carbohydrate digestion?
A) α-glucosidase
B) Sucrase
C) α-amylase
D) Lactase

Correct Answer: C) α-amylase

Explanation: α-amylase is a pancreatic enzyme that specifically breaks down starch into simpler sugars during