Metabolism: Catabolism and Anabolism

Metabolism

• Metabolism is the interconversion of biomolecules using chemical reactions, also known as biotransformation.
• It can be subdivided into catabolism and anabolism.

Catabolism

• Catabolic degradation reactions produce:
  • Chemical energy (ATP)
  • Ion gradients
  • Mechanical energy (muscle contraction)
  • Reducing agents (NADH and NADPH)

Anabolism

• Anabolic (biosynthetic) reactions:
  • Store energy
  • Produce macromolecules and cellular structures

Metabolic Reactions

• Biological reactions are in a state of flux.
• Many reactions are endothermic and unfavourable, so they need energy from ATP hydrolysis.
• Metabolism needs to balance energy (ATP), reducing agents, and the amounts of small molecules.

Biosynthetic Reactions

• Typically convert between reduced and oxidized forms.
• NAD stands for Nucleotide Adenine Dinucleotide.

Glycolysis

• Glycolysis is the degradation of glucose in the cytosol.
• It consists of 3 stages.

First Half of Glycolysis

• Glucose is phosphorylated to Glucose-6-phosphate.
• Glucose-6-phosphate is isomerized to Fructose-6-phosphate.
• Fructose-6-phosphate is converted to Fructose-1,6-bisphosphate.

Second Half of Glycolysis

• Fructose-1,6-bisphosphate is converted to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate.
• Dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate.
• Each step is repeated twice as 2x glyceraldehyde-3-phosphate molecules are generated for each glucose molecule.

Net Products of Glycolysis

• 2 ATP
• 2 NADH
• 2 pyruvate

Control Factor in Glycolysis

• Phosphofructokinase 1 enzyme mediates flux through the glycolytic pathway.

Anaerobic Respiration

• Occurs in muscle during anaerobic exercise.
• Pyruvate is reduced to R-lactate in the absence of oxygen.
• NADH is oxidized to NAD+, which allows glycolysis to continue under anaerobic conditions.
• R-lactate can be reoxidized to pyruvate using NAD+.

Cori Cycle

• Recycles R-lactate to glucose.
• Steps:
  • Lactate is transported from muscle to liver in the blood.
  • Lactate is converted to pyruvate by lactate dehydrogenase.
  • Pyruvate is converted to glucose by gluconeogenesis in the liver.
• 6 ATP are needed for the Cori Cycle, with 2 ATP coming from glycolysis.

Gluconeogenesis

• Biosynthesis of glucose from non-carbohydrate precursors in liver cytosol.
• Occurs in liver cytosol, with the exception of the oxaloacetate step, which occurs in liver mitochondria.
• Steps:
  • R-lactate is converted to pyruvate.
  • ATP, CO2, and pyruvate make oxaloacetate in mitochondria.
  • Oxaloacetate is exported to cytosol and converted to phosphoenolpyruvate.
  • Bisphosphatase and phosphatase convert fructose-1,6-bisphosphate to glucose.

Enzymes

• Lactate dehydrogenase converts R-lactate to pyruvate.
• Pyruvate carboxylase controls the balance between degradation and synthesis of glucose.
• Phosphatase allows the export of glucose to other tissues.

Mitochondria

• Roles:
  • Aerobic respiration
  • Deamination and urea formation