Metabolism Overview M2P Course 2024

Metabolism Overview and Objectives

• Aldolase B deficiency has severe effects compared to fructokinase deficiency due to significant ATP depletion after fructose, sucrose, or sorbitol ingestion.
• Energetic imbalances in cells do not violate the first and second laws of thermodynamics; cells maintain energy balance through heat generation that increases overall entropy.
• Spontaneity of a reaction can be predicted by its change in free energy (𝚫G); negative 𝚫G indicates a spontaneous reaction, while positive requires energy input.
• Exergonic reactions release energy (negative 𝚫G), while endergonic reactions absorb energy (positive 𝚫G).
• Coupling endergonic reactions with ATP hydrolysis makes them thermodynamically favorable, allowing otherwise unfavorable reactions to proceed.

Disorders of Fructose Metabolism

• Fructokinase deficiency:

  • Autosomal recessive disorder leading to fructose accumulation in urine.
  • Generally benign, affecting approximately 1 in 30,000 live births.

• Aldolase B deficiency:

  • Autosomal recessive disorder, prevents conversion of fructose 1-P into glyceraldehyde and dihydroxyacetone phosphate.
  • More severe than fructokinase deficiency, affects around 1 in 20,000 live births.
  • Symptoms include renal dysfunction, hyperuricemia, hypoglycemia, lactic acidemia, liver failure, jaundice, and can lead to death upon ingestion of fructose.

Metabolism and Thermodynamics

• The first law of thermodynamics states that energy is conserved; it cannot be created or destroyed.
• The second law indicates that entropy in a system increases over time; cells increase order while balancing entropy changes in their environment.
• A decrease in cellular entropy necessitates the release of heat to maintain overall energy balance.

Chemical Reactions and Free Energy

• Gibbs free energy (G) indicates the work potential of a reaction; 𝚫G changes as reactions occur.
• At equilibrium, 𝚫G equals zero; reactions with negative 𝚫G proceed spontaneously, while positive 𝚫G reactions need energy input.
• ATP deficiency disrupts critical cellular functions, including enzyme activity and ion balance, leading to cell swelling and potential rupture.

Metabolic Pathways

• Metabolic pathways consist of anabolic (storage) and catabolic (mobilization) reactions.
• High glucose levels lead to storage for future energy needs; conversely, low glucose levels trigger mobilization of stored energy.
• ATP/NADH/NADPH generation is vital for maintaining metabolic processes.

Intermediary Metabolism

• Pathways are interlinked; regulated and reversible steps play crucial roles in metabolic control.
• Key reactions include hydrolysis of complex molecules in catabolic processes and synthesis of complex products in anabolic reactions.
• Catabolic reactions: Breakdown of molecules (e.g., proteins to amino acids) and oxidation reactions generating ATP.
• Anabolic reactions: Synthesis of complex products from simpler substrates, requiring energy input typically involving NADPH for high-energy electrons.

Energy Density of Fats vs. Carbohydrates

• Fats are more energy dense than carbohydrates due to greater hydrogen content and higher caloric yield per gram.
• In a typical 70 kg male: approximately 30 kg of muscle and 10 kg of fat illustrate fuel reserves during metabolic processes.

This quiz focuses on key concepts of metabolism relevant to the M2P Course. It covers topics such as energy in the cell, aldolase B and fructokinase deficiencies, and the laws of thermodynamics. Additionally, it addresses spontaneous reactions and the distinction between exergonic and endergonic reactions.