Lecture 4

Gluconeogenesis and Pentose Phosphate Pathway

  • Feeder Pathways of Glycolysis:

  • Carbohydrates other than glucose can enter glycolysis at different points.

  • (reverse of gycolysis) Gluconeogenesis:

  • Definition: Synthesis of glucose from simpler compounds.

  • Importance: Provides glucose during fasting or prolonged exercise.

  • Pentose Phosphate Pathway:

  • Role: Synthesis of ribose (a nucleotide precursor) and NADPH.

Glycolysis Overview

Preparatory Phase

  • Main processes:

  • Phosphorylation of glucose:

    • Glucose → Glucose 6-phosphate (using ATP).

    • Catalyzed by Hexokinase.

  • Isomerization:

    • Glucose 6-phosphate ↔ Fructose 6-phosphate (catalyzed by Phosphohexose isomerase).

  • Further phosphorylation:

    • Fructose 6-phosphate → Fructose 1,6-bisphosphate (using ATP).

    • Catalyzed by Phosphofructokinase-1 (PFK-1).

  • Cleavage of sugar:

    • Fructose 1,6-bisphosphate → Glyceraldehyde 3-phosphate (G3P) + Dihydroxyacetone phosphate (DHAP) (via Aldolase).

Payoff Phase

  • Energy extraction:

  • G3P undergoes oxidation and phosphorylation:

    • Producing 1,3-Bisphosphoglycerate (using NAD+).

  • First substrate-level phosphorylation:

    • 1,3-Bisphosphoglycerate → 3-Phosphoglycerate + ATP (via Phosphoglycerate kinase).

  • Second substrate-level phosphorylation:

    • Phosphoenolpyruvate → Pyruvate + ATP (via Pyruvate kinase).

Feeder Pathways for Glycolysis

  • Sources of carbohydrates:

  • D-Glucose: Broken down via hexokinase.

  • D-Fructose: Metabolized in the liver. Converts to Fructose 1-phosphate (via Fructokinase), then to DHAP and G3P.

  • Trehalose: Hydrolyzed by Trehalase, then enters glycolysis.

  • D-Mannose: Converted to Mannose 6-phosphate (via hexokinase).

Anaerobic Conditions

  • Yeast Fermentation:

  • Converts glucose to ethanol and CO2.

  • Enzymes require cofactors:

    • Pyruvate decarboxylase (requires Mg++, thiamine pyrophosphate).

    • Alcohol dehydrogenase (requires Zn++, NAD+).

  • Animal Muscle Function:

  • Under strenuous exercise, pyruvate is reduced to lactate, regenerating NAD+, allowing glycolysis to continue.

Gluconeogenesis: Precursors and Pathway Comparison draw the diagram

  • Key precursors for gluconeogenesis:

  • Pyruvate

  • Lactate

  • Glycerol

  • Glucogenic amino acids

  • Glyceraldehyde 3-phosphate.

  • Glycolysis vs. Gluconeogenesis:

  • Glycolysis occurs primarily in muscles and brain, while gluconeogenesis mainly occurs in the liver.

  • Different enzymes catalyze the steps unique to each pathway.

Regulation of Glycolysis and Gluconeogenesis

  • Enzymatic regulation is crucial for maintaining homeostasis in metabolic pathways.

  • ATP serves as an inhibitor for PFK-1 in glycolysis, while it stimulates fructose 1,6-bisphosphatase in gluconeogenesis.

  • Feedback inhibition ensures that the pathways do not run concurrently unnecessarily, conserving resources.

Pentose Phosphate Pathway Functions

  • Main products:

  • NADPH for reductive biosynthesis of lipids and nucleotides.

  • Ribose-5-phosphate for nucleotide synthesis.

  • Importance in rapidly dividing cells:

  • Tissue involved in fatty acid synthesis and red blood cells exposed to oxygen.

Summary of Key Metabolic Pathways

  • Glycolysis extracts energy from glucose and processes it anaerobically.

  • Pentose phosphate pathway generates NADPH for synthesis.

  • Gluconeogenesis synthesizes glucose from various metabolites, maintaining blood glucose levels during fasting.

Bread Making Steps

  1. Ingredient Preparation:

  • Primary ingredients include:

    • Flour: Main structure provider, containing gluten proteins.

    • Water: Hydrates flour, allowing gluten development.

    • Salt: Enhances flavor and controls fermentation rate.

    • Yeast: Mainly Saccharomyces cerevisiae, responsible for fermentation.

    • Sugars:

      • Sucrose: Common sugar, breaks down into glucose and fructose, providing immediate energy for yeast.

      • Glucose: Simple sugar, directly utilized by yeast during fermentation.

      • Maltose: Formed during the mashing of malted grains, further broken down for fermentation.

  1. Mixing:

  • Ingredients are combined to activate gluten, providing dough structure.

  • Yeast begins consuming free sugars, leading to early fermentation.

  1. Fermentation (Proofing):

  • Yeast enzymes (invertase and maltase) convert sugars into fermentable forms:

    • Invertase: Breaks down sucrose into glucose and fructose.

    • Maltase: Converts maltose into two glucose molecules.

  • Carbon Dioxide (CO2) production increases, causing dough to rise.

  1. Punching Down:

  • Releases excess CO2 and redistributes yeast for uniform fermentation.

  1. Shaping:

  • Promotes further gluten development, helping maintain structure during rising.

  1. Final Proofing:

  • Dough rises again, allowing yeast to consume remaining sugars and produce more CO2, enhancing volume.

  1. Baking:

  • Begins around 140°F (60°C), where heat denatures proteins and starches.

  • Yeast becomes inactive, setting the bread's structure.

  • The Maillard reaction enhances flavor and color in the crust.

  1. Cooling:

  • Important for texture: moisture must escape to achieve the desired crust and crumb structure.

Dynamic Steady State

Dynamic steady state refers to a condition in biological systems where, despite continuous changes and biochemical processes, the overall state remains constant over time. This concept is crucial in understanding metabolic pathways and homeostasis in living organisms. At dynamic steady state, the rates of production and consumption of substrates and products are balanced, allowing the organism to maintain stable internal conditions despite fluctuations in external environments.

Key points about dynamic steady state include:

  • Continuous Flux: Substrates are constantly being converted into products, yet the concentrations of these metabolites remain relatively stable due to efficient regulatory mechanisms.

  • Metabolic Regulation: Enzymes and pathways are tightly controlled; feedback mechanisms and signaling molecules play essential roles in adjusting the rates of metabolic reactions.

  • Homeostasis: This state supports physiological processes crucial for sustaining life, enabling organisms to respond effectively to changes in their environment while maintaining critical functions such as growth, reproduction, and cellular repair.