Lecture Notes on Metabolic Pathways

Glycolysis

• Glycolysis involves breaking down sugar (glucose).
• Reactant: Glucose - the starting molecule; not a product of glycolysis.
• Products:
  • Pyruvate
  • Acetyl CoA
  • Lactate
• When there's an excess of glucose, it's stored as glycogen in the liver.

Gluconeogenesis

• Gluconeogenesis is the reverse process of glycolysis, creating glucose from other compounds.
• Occurs when glucose levels are low (not just during starvation).
• The liver stores glycogen, which can be broken down into glucose during gluconeogenesis.

Blood Glucose Regulation

• Blood glucose levels are carefully regulated by insulin and glucagon.
  • Insulin: Increases when eating, facilitating glucose uptake by cells.
  • Glucagon: Increases when hungry, signaling glycogen breakdown to release glucose.
• Insulin and glucagon work inversely to maintain glucose homeostasis.
• Insulin facilitates glucose transport into most cells, except brain cells.
  • The brain can take up glucose freely without insulin's help.

Gluconeogenesis substrates

• Lactate
• Amino acids (from protein)
• Fats

Cori Cycle

• The Cori Cycle occurs when muscles are at rest.
• It contributes to glucose levels but at a reduced rate compared to when muscles are active.

Fatty Acids and Energy

• Fatty acids are broken down into acetyl CoA units to generate energy.
• This process converts ATP to AMP, releasing two phosphate groups and a significant amount of energy: ATP \rightarrow AMP
• Fatty acids are a backup energy source, utilized when carbohydrate (sugar) availability is low.
  • A long chain is broken down to produce acetyl CoA which is then used to make ATP.

Ketone Bodies & Ketogenesis

• When carbohydrate availability is insufficient, the body turns to triglycerides (fats).
• Beta-oxidation of fatty acids produces a large amount of acetyl CoA.
• Because fatty acids have $\approx$ nine acetyl CoA units. Compared to glucose which has two.
• If the citric acid cycle can't process all the acetyl CoA, ketone bodies are formed (ketogenesis).
• Excess ketone bodies lead to ketosis.
• Acetone is a type of ketone body - byproduct of ketone bodies.
• Small amounts of ketone bodies are normal; large amounts are problematic.

Ketoacidosis

• Ketoacidosis occurs when there is a buildup of acid in the blood and urine, lowering the pH.
• Severely low blood pH denatures proteins and damages organs, especially the kidneys.
• It can also affect the brain, potentially leading to a coma as a protective mechanism.

Keto Diet

• A keto diet is considered safe because protein intake moderates the metabolic activities, preventing severe acidosis.

Diabetic Ketoacidosis

• Cause: In diabetics, glucose may not enter cells due to lack of insulin or insulin resistance even if glucose is present in the blood.
• Brain: The brain has enough glucose but the acidity in the blood that goes to the brain causing the brain pH very low and it goes into coma.
• The cells are essentially starving, leading to ketogenesis.

Starvation

• A person can survive about a week without food, provided they have water.

Treatment

• Treatments for ketoacidosis focus on correcting acidity and restoring glucose metabolism through fluid and electrolyte replacement.

Metabolic Fates of Glucose

• Glycolysis breaks down glucose to three major products:
  • Pyruvate
  • Acetyl CoA
  • An intermediate -> Lactate or other intermediates.
• The normal pathway does not produce glucose, only gluconeogenesis can.