Lecture 7 and 8: Carbohydrate Metabolism (Glucose Catabolism)

ANFS 475/675: Lecture 7 and 8 - Carbohydrate Metabolism (Glucose Catabolism)

Overview of Glycolysis

  • First Process: Glycolysis is the first metabolic pathway that allows the breakdown of glucose.

  • Location: Occurs in the cytosol of the cell.

  • Anaerobic Process: Does not require oxygen (anaerobic).

  • Energy Production: Produces ATP, which is energy currency for the cell.

Glycolysis Pathway

Breakdown Pathway

  • Substrates Involved:

    • Glucose

    • ATP and ADP

    • Mg2+

  • Main Products:

    • Pyruvate (final product)

    • NADH (reduced coenzyme)

    • ** ATP** (net gain of 2 ATP molecules)

Steps of Glycolysis

  1. Hexokinase (HK)

    • Converts Glucose to Glucose-6-phosphate (G6P).

    • Reaction: Glucose + ATP → G6P + ADP

    • Enzyme: Hexokinase.

    • Enzyme Function: Uses one ATP.

  2. Phosphoglucose Isomerase (PGI)

    • Converts G6P to Fructose-6-phosphate (F6P).

    • No energy used.

  3. Phosphofructokinase (PFK)

    • Converts F6P to Fructose-1,6-bisphosphate (FBP).

    • Reaction: F6P + ATP → FBP + ADP + H+

    • Key Role: Rate-controlling step, uses second ATP.

  4. Aldolase

    • Splits FBP into two products:

      • Dihydroxyacetone phosphate (DHAP)

      • Glyceraldehyde-3-phosphate (GAP)

    • No energy used.

  5. Triose Phosphate Isomerase (TIM)

    • Interconverts GAP and DHAP.

    • Plays a crucial role in the further processing of the two products.

ATP Generation

  1. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

    • Converts GAP to 1,3-Bisphosphoglycerate (1,3-BPG).

    • NAD+ is converted to NADH and inorganic phosphate (Pi) is added.

  2. Phosphoglycerate Kinase (PGK)

    • Converts 1,3-BPG to 3-Phosphoglycerate (3PG).

    • Reaction: 1,3-BPG + ADP → 3PG + ATP

    • ATP Generation: First ATP produced.

  3. Phosphoglycerate Mutase (PGM)

    • Converts 3PG to 2-Phosphoglycerate (2PG).

  4. Enolase

    • Converts 2PG to Phosphoenolpyruvate (PEP).

    • Dehydration Reactions: Produces water.

  5. Pyruvate Kinase (PK)

    • Converts PEP to Pyruvate.

    • Reaction: PEP + ADP → Pyruvate + ATP

    • Key ATP Generation: Final ATP produced, net gain of 2 ATP from glycolysis.

Stages of Glycolysis

  • First Stage: Energy Investment

    • Involves phosphorylation and isomerization, consumes energy (invests ATP).

  • Second Stage: Energy Recovery

    • ATP generated (substrate-level phosphorylation).

Summary of Glycolysis

  • Process Overview: Glycolysis breaks down glucose to pyruvate while using released energy to synthesize ATP from ADP and Pi.

  • Net Production: Glycolysis results in a net gain of 2 ATP per glucose molecule and produces 2 NADH.

Fermentation: Anaerobic Fate of Pyruvate

Metabolic Fate of Pyruvate

  • **Three Routes: **

    • Oxidative Phosphorylation: Leads to cellular respiration.

    • Lactate in Muscles: Pyruvate is reduced to lactate in anaerobic conditions, regenerating NAD+ for glycolysis.

    • Alcoholic Fermentation in Yeast: Produces ethanol and CO2.

Reactions of Alcoholic Fermentation

  1. Pyruvate Decarboxylase: Converts pyruvate to Acetaldehyde (loses CO2).

  2. Alcohol Dehydrogenase: Converts acetaldehyde to Ethanol (regenerates NAD+).

Regulation of Glycolysis

  • Key Enzyme: Phosphofructokinase (PFK) is the main regulatory point of glycolysis.

  • Allosteric Regulation: Activated by AMP and ADP, inhibited by ATP.

  • Flux-Control Point: Enzymes with large negative free energy changes act as flux control points in metabolic pathways.

Metabolism of Other Hexoses (Fructose, Galactose, Mannose)

  • Fructose: Utilized differently in muscle (hexokinase) and liver (fructokinase).

  • Galactose: Converted via galactokinase to galactose-1-phosphate leading to glycolytic intermediates.

  • Mannose: Metabolized into mannose-6-phosphate, which is converted to fructose-6-phosphate.

Pentose Phosphate Pathway (PPP)

  • Purpose: Produces NADPH for biosynthesis and Ribose-5-phosphate for nucleotide synthesis.

  • Stages: Involves dehydrogenase reactions that lead from G6P to ribulose-5-phosphate through multiple intermediates like 6-phosphogluconate.

Summary of Key Concepts

  1. Energy Investment vs. Energy Recovery: Glycolysis has a net gain of ATP.

  2. Regulatory Mechanisms: PFK is the major control point influenced by energy status of the cell.

  3. Intermediary Metabolism: Other sugars can enter the glycolytic pathway at various points.

  4. Pentose Pathway: Integrates with glycolysis, showing interconnected metabolic pathways.