Week 2 -L4- Study Notes on Metabolic States and Regulation

Overview of metabolic states: fed state, fasting state, starvation state, and disease states (specifically diabetes).
Purpose: Explore metabolic pathways and levels of regulation active during these states.

Definition: The state of metabolism approximately up to four hours after a meal.
Referred to as "lipogenic liver."
Key considerations:
- Timeframes are relative and variable based on individual factors (fuel reserves, meal size, activity level).

Blood glucose levels spike after a meal, stimulating insulin secretion.
Insulin promotes:
- Glycolysis (glucose oxidation).
- Glycogen synthesis (storage of glucose).
Effects of insulin:
- Decreases blood glucose concentration by facilitating glucose uptake.
After 2-4 hours, blood glucose levels start to decline:
- Glucagon is secreted to regulate glucose levels; stimulates slight glucose release (from glycogen stores).
Early Fasting Stage (postprandial, approximately 4 hours after a meal):
- Increased glucagon secretion.
- Hydrolyzes triacylglycerides (TAGs), releasing fatty acids for muscle and liver utilization.

Illustration depicting:
- Absorption of glucose, amino acids, and fats from the gastrointestinal tract into the bloodstream.
- Increased blood levels of glucose, amino acids, and fats.
Pathways involved:
- Glucose:
- Stored as glycogen.
- Exported to the brain for energy (brain prefers glucose).
- Broken down via glycolysis to pyruvate, stored as TAGs.
- Amino Acids:
- Undergo transamination in the liver.
- Most are broken down into alpha-keto acids (for energy production or repurposing).
- Fats:
- Fatty acids serve as fuel for muscles and liver.
- Stored as TAGs in adipose tissue.

Definition: Approximately 4 hours after a meal; referred to as "glucogenic liver."
Blood glucose levels drop post-fed state begins.
Key metabolic changes:
- Muscles use amino acids for energy via transamination or deamination.
- Glucogenic amino acids are converted to glucose via gluconeogenesis (to supply the brain, which requires glucose).

Definition: Skipping several meals or going days without food.
Shift in fuel usage:
- Muscle proteins are used as a fuel source.
- Fatty acids are oxidized to acetyl CoA, fueling the citric acid cycle.
Importance of oxaloacetate:
- Oxaloacetate is essential for gluconeogenesis.
- When gluconeogenesis is active, it limits the citric acid cycle's ability to proceed with fatty acid oxidation.

Under starvation conditions:
- Fatty acids are converted to ketone bodies in the liver (acetone, hydroxybutyrate, acetoacetate).
- Ketone bodies serve as an alternative fuel source for the brain, muscles, and liver.
Historical significance: Acetone scent in breath used for diagnosing diabetes due to high ketone levels.

Loss of gastrointestinal input:
- Body relies on existing tissue energy stores.
Glucagon's role in mobilizing triacylglycerides:
- Stored TAGs converted to fatty acids for liver and muscle energy.
Breakdown of glycogen and fat:
- Glycogen stores last approximately 24 hours before depletion.
- After glycogen depletion, gluconeogenesis maintains glucose levels through available precursors.
Protein breakdown is a last resort to prevent loss of essential functions.

Graph showing usage of fuel sources over starvation periods:
- Glucose levels drop and plateau after a few days, maintained by gluconeogenesis.
- Fatty acid levels increase as TAGs are mobilized.
- Ketone bodies rise significantly after several days of starvation, intensifying until approximately 40 days.

Overview of type 1 diabetes:
- Characterized by absent insulin function.
- Symptoms and metabolic effects resemble prolonged fasting, highlighting the significant connection between metabolic states and diabetic conditions.
Importance of understanding metabolic shifts during starvation to comprehend diabetic states in the upcoming discussions.