10.3 Alternative pathways and metabolic regulation

Cellular respiration isn't just about making energy. It's a complex dance of molecules, carefully regulated to keep our cells running smoothly. When oxygen is scarce, fermentation steps in, allowing cells to keep producing ATP and recycling crucial molecules.

But it doesn't stop there. Our bodies have clever ways to balance energy production and use. From enzyme regulation to hormonal control, these systems work together to keep us going, whether we're sprinting or sleeping.

Fermentation and Anaerobic Metabolism

Fermentation pathways for NAD+ regeneration

• Fermentation pathways serve as alternative metabolic routes occurring in the absence of oxygen enabling continued ATP production without oxidative phosphorylation
• Regenerate NAD+ from NADH, a crucial electron acceptor in glycolysis, preventing glycolysis from halting due to NAD+ depletion
• Lactic acid fermentation reduces pyruvate to lactate via lactate dehydrogenase, oxidizing NADH to NAD+ (skeletal muscle cells)
• Alcoholic fermentation decarboxylates pyruvate to acetaldehyde, then reduces it to ethanol by alcohol dehydrogenase, oxidizing NADH to NAD+ (yeast cells)

Cori cycle for lactate recycling

• Metabolic pathway recycling lactate produced by anaerobic tissues (skeletal muscles) back to glucose in the liver
• During intense exercise, skeletal muscles undergo anaerobic respiration, releasing lactate into the bloodstream for transport to the liver
• Liver converts lactate back to pyruvate via lactate dehydrogenase, then uses pyruvate in gluconeogenesis to synthesize glucose
• Newly synthesized glucose released into the bloodstream for use by muscles and other tissues
• Maintains glucose homeostasis and prevents lactate accumulation in the blood

Regulation of Cellular Respiration

Regulation of cellular respiration

• Allosteric enzymes regulate cellular respiration with regulatory sites distinct from active sites
  • Allosteric activators (AMP, ADP, fructose-2,6-bisphosphate) enhance enzyme activity
  • Allosteric inhibitors (ATP, citrate) inhibit enzyme activity
• Phosphofructokinase-1 (PFK-1) catalyzes fructose-6-phosphate to fructose-1,6-bisphosphate conversion in glycolysis
• Pyruvate dehydrogenase complex (PDC) catalyzes pyruvate to acetyl-CoA conversion, linking glycolysis to the citric acid cycle
  • Allosteric inhibitors of PDC: acetyl-CoA, NADH, ATP
• Feedback inhibition maintains homeostasis by end product accumulation inhibiting earlier pathway enzymes, reducing its own production

Insulin vs glucagon in glucose regulation

• Insulin and glucagon regulate blood glucose levels and cellular respiration
• Insulin released by the pancreas when blood glucose levels are high
  1. Promotes glucose uptake by liver, skeletal muscles, and adipose tissue cells
  2. Stimulates glycolysis and glycogenesis (glucose storage as glycogen)
  3. Inhibits gluconeogenesis and glycogenolysis (glycogen breakdown to glucose)
• Glucagon released by the pancreas when blood glucose levels are low
  1. Stimulates glycogenolysis and gluconeogenesis in the liver, increasing blood glucose
  2. Promotes lipolysis (lipid breakdown) in adipose tissue, providing fatty acids for energy production
  3. Enhances cellular respiration by increasing glucose and fatty acid availability for oxidation
• Balance between insulin and glucagon maintains normal blood glucose range and regulates cellular respiration accordingly