In-Depth Notes on Metabolism

Metabolism Overview

  • Focus on pathways, structures, enzymes, cofactors, and products.
    • Key Pathways to Know:
    • Glycolysis
    • Gluconeogenesis
    • Glucose-UDP synthesis
    • Pentose phosphate pathway (oxidative stage)
    • Pyruvate dehydrogenase
    • Citric acid cycle
    • β-oxidation

Glycolysis

  • Energy Investment Phase:

    • Steps:
      1. Hexokinase: Converts Glucose to Glucose-6-phosphate using ATP.
        • Reaction: Glucose + ATP → Glucose-6-phosphate + ADP
      2. Phosphoglucose isomerase: Converts Glucose-6-phosphate to Fructose-6-phosphate.
      3. Phosphofructokinase: Converts Fructose-6-phosphate to Fructose-1,6-bisphosphate (key regulatory step, uses ATP).
      4. Aldolase: Cleaves Fructose-1,6-bisphosphate into Glyceraldehyde-3-phosphate and Dihydroxyacetone phosphate.
      5. Triose phosphate isomerase: Interconverts Glyceraldehyde-3-phosphate and Dihydroxyacetone phosphate.

  • Energy Payoff Phase:

    • Steps:
      1. GAP dehydrogenase: Converts Glyceraldehyde-3-phosphate to 1,3-Bisphosphoglycerate; produces NADH.
      2. Phosphoglycerate kinase: Converts 1,3-Bisphosphoglycerate to 3-Phosphoglycerate; produces ATP (substrate-level phosphorylation).
      3. Phosphoglycerate mutase: Converts 3-Phosphoglycerate to 2-Phosphoglycerate.
      4. Enolase: Converts 2-Phosphoglycerate to Phosphoenolpyruvate.
      5. Pyruvate kinase: Converts Phosphoenolpyruvate to Pyruvate; produces ATP.

Gluconeogenesis

  • Overview: Formation of glucose from pyruvate or oxaloacetate; employs reversible glycolysis enzymes and four new enzymes:

    • 1. Pyruvate carboxylase
    • 2. Phosphoenolpyruvate carboxykinase
    • 3. Fructose bisphosphatase
    • 4. Glucose-6-phosphatase

  • Steps of Conversion from Pyruvate to PEP:

    1. Pyruvate is converted to oxaloacetate (uses ATP).
    2. Oxaloacetate is converted to Phosphoenolpyruvate (uses GTP).

Glucose-UDP Synthesis

  • Glucose-6-phosphate is converted to Glucose-1-phosphate and then activated by UTP to produce UDP-glucose and inorganic phosphate.
    • Key Reaction: Glucose-6-phosphate + UTP → UDP-glucose + PPi

Pentose Phosphate Pathway

  • Stages:
    1. Oxidative Stage: Produces NADPH and ribulose-5-phosphate.
    2. Non-oxidative Stage: Ribulose-5-phosphate is converted to fructose-6-phosphate and glyceraldehyde-3-phosphate.

Pyruvate Dehydrogenase Reaction

  • Overview: Converts Pyruvate to Acetyl-CoA
    • Utilizes NAD+, produces NADH and CO2.
    • Reaction: Pyruvate + CoA + NAD+ → Acetyl-CoA + CO2 + NADH

Citric Acid Cycle (TCA Cycle)

  • Overview: Acetyl-CoA condenses with oxaloacetate to form citrate.
    • Yield per cycle: 3 NADH, 1 QH2, and 1 GTP (ATP).

β-Oxidation

  • Overview: Fatty acids are oxidized to form Acetyl-CoA.
    • Steps include:
    1. Oxidation at 2,3 position
    2. Hydration
    3. Further oxidation
    4. Thiolysis to release Acetyl-CoA

Mechanisms to Know

  • Important Enzyme Mechanisms:

    • Aldolase
    • GAP dehydrogenase
    • Phosphoglycerate mutase
    • Pyruvate Dehydrogenase
    • Succinyl-CoA Synthetase
    • Ketoacyl-ACP Synthase (KS)

  • Example Mechanism of Aldolase:

    1. Nucleophilic attack of carbonyl by lysine amine → covalent intermediate.
    2. Water loss → Schiff Base formation.
    3. Tyrosine abstracts proton (base catalysis).
    4. Cleavage of C3-C4 bond → GAP released.
    5. Hydrolysis of Schiff base regenerates active site.

Summary

  • Comprehensive overview of metabolism pathways including glycolysis, gluconeogenesis, citric acid cycle, pentose phosphate pathway, and β-oxidation is essential for understanding energy production and biosynthesis processes in cells.