Carbohydrate Metabolism

Overview of Carbohydrates

  • Roles of Carbohydrates:
    • Energy sources
    • Structural elements in living cells
  • Focus on glucose as a key energy source.
    • Techniques for synthesis, degradation, and storage.

1. Metabolism and Jet Engines

  • Introduction to carbohydrate metabolism with an outline of topics.

2. Glycolysis

2.1 The Reactions of the Glycolytic Pathway
  • Glycolysis is a universal pathway found in nearly all organisms and includes the following steps:
    • Step 1: Glucose to Glucose-6-Phosphate (G6P).
    • Enzyme: Hexokinase (HK)
    • Reaction: Glucose + ATP → G6P + ADP
    • Step 2: G6P to Fructose-6-Phosphate (F6P).
    • Enzyme: Phosphoglucose Isomerase (PGI)
    • Reversible reaction.
    • Step 3: F6P to Fructose-1,6-Bisphosphate (F1,6BP).
    • Enzyme: Phosphofructokinase-1 (PFK-1)
    • Reaction: F6P + ATP → F1,6BP + ADP (irreversible)
    • Committed step of glycolysis and regulated.
    • Step 4: Aldol cleavage of F1,6BP into GAP and Dihydroxyacetone phosphate (DHAP).
    • Enzyme: Aldolase.
    • Step 5: Interconversion of GAP and DHAP using Triose Phosphate Isomerase.
    • Step 6: Oxidation of GAP to Glycerate-1,3-Bisphosphate (1,3BPG).
    • Enzyme: Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH)
    • NAD+ → NADH + H+
    • Step 7: Transfer of phosphate from 1,3BPG to ADP, yielding ATP and Glycerate-3-Phosphate (3PG).
    • Enzyme: Phosphoglycerate Kinase.
    • ATP produced through substrate-level phosphorylation.
    • Step 8: Conversion of 3PG to 2-Phosphoglycerate (2PG).
    • Enzyme: Phosphoglycerate Mutase.
    • Step 9: Dehydration of 2PG to Phosphoenolpyruvate (PEP).
    • Enzyme: Enolase.
    • Step 10: Conversion from PEP to Pyruvate.
    • Enzyme: Pyruvate Kinase (PK)
    • Reaction: PEP + ADP → Pyruvate + ATP (irreversible).
2.2 The Fates of Pyruvate
  • Anaerobic Pathways:
    • Pyruvate → Lactate (Muscle cells, red blood cells).
    • Pyruvate → Ethanol (yeast fermentation).
  • Aerobic Pathways:
    • Pyruvate → Acetyl-CoA → Citric Acid Cycle.
2.3 The Energetics of Glycolysis
  • Oxidation of glucose to pyruvate generates energy in the form of:
    • 2 ATP (net)
    • 2 NADH.
  • Efficiency: About 5% of total energy stored in glucose is captured in ATP.
2.4 Regulation of Glycolysis
  • Regulation through key enzymes:
    • Hexokinase: Inhibited by G6P.
    • PFK-1: Allosterically activated by AMP, inhibited by ATP, citrate, fructose-2,6-bisphosphate.
    • Pyruvate Kinase: Activated by fructose-1,6-bisphosphate; inhibited by ATP, acetyl-CoA, alanine.

3. Gluconeogenesis

3.1 Gluconeogenesis Reactions
  • Synthesis of glucose from non-carbohydrate precursors (lactate, pyruvate, certain amino acids).
  • Unique enzymes to bypass irreversible glycolysis steps:
    • Pyruvate Carboxylase: Converts pyruvate to Oxaloacetate (OAA).
    • PEP Carboxykinase: Converts OAA to PEP.
    • Fructose-1,6-bisphosphatase: Converts F1,6BP to F6P.
    • Glucose-6-phosphatase: Converts G6P to glucose.
3.2 Regulation of Gluconeogenesis
  • Stimulated by high levels of lactate, glycerol, and amino acids.
  • Hormonal and allosteric regulation similar to glycolysis:
    • High Acetyl-CoA activates pyruvate carboxylase.
    • Citrate stimulates Fructose-1,6-bisphosphatase.
    • AMP and fructose-2,6-bisphosphate inhibit Fructose-1,6-bisphosphatase.

4. The Pentose Phosphate Pathway

4.1 Overview
  • Function: Produces NADPH and ribose-5-phosphate, not ATP.
4.2 Oxidative Phase
  • Glucose-6-phosphate → Ribulose-5-phosphate, generating 2 NADPH.
4.3 Non-Oxidative Phase
  • Interconversion of ribose-5-phosphate to glycolytic intermediates (GAP, fructose-6-phosphate).

5. Metabolism of Other Important Sugars

5.1 Fructose Metabolism
  • Fructose enters glycolysis as fructose-1-phosphate via fructokinase, leading to glyceraldehyde and DHAP.
5.2 Galactose and Mannose
  • Galactose → Galactose-1-phosphate (via galactokinase)
  • Mannose → Mannose-6-phosphate (via hexokinase)

6. Glycogen Metabolism

6.1 Glycogenesis
  • Conversion of glucose-6-phosphate to glycogen.
6.2 Glycogenolysis
  • Breakdown of glycogen into glucose-1-phosphate.
6.3 Regulation by Hormones
  • Controlled by insulin, glucagon, epinephrine, and allosteric regulators.

7. Chapter Summary

  • Overview of pathways and regulatory mechanisms of carbohydrate metabolism, dominance of glycolysis, and importance of gluconeogenesis, pentose phosphate pathway, and regulation of glycogen metabolism.