Bioenergetics L12 Starvation Flashcards
Overview of the five phases of glucose homeostasis in humans
Phase I (0–4 hours) - Exogenous Glucose:
Glucose Origin: In this phase, glucose comes from food (exogenous source), specifically from carbohydrates ingested during a meal. This is the dominant source of glucose in the bloodstream immediately after eating.
Glucose Utilization: All tissues in the body, including the brain, muscles, and other organs, use glucose as their primary fuel.
Major Fuel for the Brain: Glucose is the main source of energy for the brain in this phase.
Phase II (4–16 hours) - Glycogen Breakdown:
Glucose Origin: As the exogenous glucose is used up, the body switches to glycogenolysis—the breakdown of glycogen stored in the liver into glucose. A small amount of glucose is also produced by hepatic gluconeogenesis (creation of glucose from non-carbohydrate sources).
Glucose Utilization: Glucose is still used by most tissues, but liver, muscle, and adipose tissues begin to reduce their glucose usage in favor of fat as an energy source to preserve glucose for essential organs like the brain.
Major Fuel for the Brain: Glucose remains the primary fuel for the brain.
Phase III (16–28 hours) - Gluconeogenesis and Glycogen Use:
Glucose Origin: As glycogen stores deplete, gluconeogenesis (the production of glucose from non-carbohydrate sources like amino acids, lactate, and glycerol) ramps up in the liver. Glycogen is still used, but its contribution diminishes.
Glucose Utilization: Glucose consumption continues to decrease in tissues like muscle and adipose tissue, while vital organs (such as the brain, red blood cells, and renal medulla) still rely on glucose. The brain is still predominantly using glucose at this stage.
Major Fuel for the Brain: Glucose remains the primary fuel.
Phase IV (2–24 days) - Gluconeogenesis Dominance:
Glucose Origin: In this phase, gluconeogenesis in both the liver and kidneys becomes the main source of glucose. Glycogen stores are nearly depleted by now.
Glucose Utilization: Tissues like the brain, red blood cells, and renal medulla continue to require glucose, but now the body starts producing ketone bodies from fat metabolism as an alternative fuel source. Muscles significantly reduce their glucose consumption.
Major Fuel for the Brain: The brain begins to rely on a combination of glucose and ketone bodies for energy.
Phase V (24–40 days) - Prolonged Fasting (Ketosis):
Glucose Origin: Glucose is produced exclusively by gluconeogenesis from hepatic and renal sources. However, ketone bodies, produced from fat metabolism, become the primary energy source.
Glucose Utilization: Glucose consumption by the brain and other tissues decreases as the reliance on ketone bodies increases. Only tissues that absolutely need glucose, such as red blood cells (which cannot use ketones) and the renal medulla, continue to use glucose.
Major Fuel for the Brain: The brain shifts more towards using ketone bodies as its main fuel, with glucose being a secondary source.
Overview of fuel choice during starvation
Left Graph: Plasma Glucose Levels during Starvation
Y-axis (Plasma Level): Represents the concentration of glucose in the blood (in millimoles per liter, mM).
X-axis (Days of Starvation): Shows the time progression from 0 to 8 days of starvation.
Trend: The glucose levels in the blood decline steadily over the first 2-3 days of starvation and then stabilize at a lower level around 3-4 mM. This indicates that the body begins conserving glucose as fasting continues, prioritizing its use for tissues like red blood cells and parts of the brain that still rely on glucose.
Right Graph: Plasma Ketone Bodies and Fatty Acids during Starvation
Y-axis (Plasma Level): Indicates the concentration of ketone bodies and fatty acids in the blood (in mM).
X-axis (Days of Starvation): Displays time progression from 0 to 8 days of starvation.
Ketone Bodies (Red Line): The level of ketone bodies (byproducts of fat metabolism) rises sharply after the first couple of days of starvation. By around day 2-3, ketone body production accelerates significantly, becoming a major energy source, especially for the brain.
Fatty Acids (Green Line): Fatty acid levels in the plasma increase slightly, but their rise is much slower and more moderate compared to ketone bodies. Fatty acids are released from adipose tissue (fat stores) and are mainly used by muscles and other peripheral tissues as an energy source.
Key Concepts:
Fuel Switching: During starvation, the body switches from primarily using glucose as an energy source to using fatty acids and ketone bodies.
Brain Metabolism: Initially, the brain relies heavily on glucose, but as glucose levels decline, the brain adapts to use ketone bodies as an alternative fuel. This switch helps conserve glucose for critical tissues like red blood cells, which cannot use ketone bodies.
Ketone Bodies (Acetone Smell): As ketone bodies increase in the blood, they may cause a noticeable “acetone” smell in the breath. Acetone is a type of ketone that is exhaled, leading to this characteristic odor during prolonged fasting or starvation.
Ketogenesis
How fats are converted into ketone bodies during prolonged periods of fasting or carbohydrate deprivation.
Ketones are released into blood, and can diffuse across membranes. Ketones are then rearranged back to acetyl CoA in cells of tissues such as the brain.
Acetone may be turned to pyruvate and lactate.
What animals do not metabolise lipids directly?
Sharks, skates, and rays use ketones as a fuel source for cruising
Why are ketone bodies used?
- Brain cannot use fat
- After 3 days of starvation, 30% of the brain’s energy is from ketone bodies (mostly from liver, astrocytes a little)
- After 40 days, 70% of ketone bodies & glucose use drops from 120 to 40g/day.
- The ketones acetoacetate and B-hydroxybutyrate are also acidic, pH of the blood drops, resulting in ketoacidosis.
What is the ketogenic diet?
Pros and Cons of ketogenic diet
Cons:
Fewer Carbs Isn’t Necessarily a Good Thing:
Explanation: Reducing carbohydrate intake might have negative effects on one’s well-being. Although it could potentially extend life, the experience might feel unpleasant or difficult due to the body’s adjustment to lower carb intake, leading to fatigue or irritability.
You May Not Be Getting Enough Sugar:
Explanation: Low-carb diets can cause individuals to feel tired or experience “brain fog” because sugar (glucose) is a primary source of energy, particularly for the brain. Without enough glucose, cognitive function may decline, leading to difficulty concentrating or feeling mentally slow.
It Could Have a Negative Impact on Heart Health:
Explanation: Many foods associated with low-carb diets, such as those high in saturated fats and meats (common in the ketogenic diet), could raise concerns about heart health. High consumption of these foods may increase cholesterol levels, potentially leading to cardiovascular issues over time.
Pros:
It Might Be Helpful for the Days Spent at Your Desk Job:
Explanation: Low-carb diets can help in reducing the risk of metabolic disorders such as diabetes, especially for people with sedentary lifestyles. For those who sit for long hours, the diet may help regulate blood sugar and insulin levels more effectively.
It May Help Prevent Cancer:
Explanation: Some research suggests that very low-carb diets may be linked to a reduction in cancer risk. Tumor cells often rely on glucose for growth, and by lowering blood sugar, some studies imply that low-carb diets could potentially limit cancer development or progression.
What is CrP
CrP stands for Creatine Phosphate (also known as phosphocreatine). It is a high-energy compound stored in muscles and plays a crucial role in the rapid regeneration of ATP (adenosine triphosphate),
Role of creatine kinase (CK) in the creatine phosphate
Key Components:
mtCK (Mitochondrial Creatine Kinase):
This enzyme is located in the mitochondria. It catalyzes the transfer of a phosphate group from ATP (produced in the mitochondria via oxidative phosphorylation) to creatine (C), forming creatine phosphate (CP).
ATP generated in the mitochondria is converted into creatine phosphate (CrP), which can easily diffuse throughout the cell because CrP is smaller and less charged than ATP (as indicated by the mass differences noted in the diagram: CP = 211 g/mole, ATP = 518 g/mole).
CP (Creatine Phosphate) Shuttle:
After being formed in the mitochondria, CP moves from the mitochondria into the cytosol. This is a more efficient energy transfer molecule than ATP because of its smaller size and quicker diffusion.
MCK (Muscle Creatine Kinase):
Once in the cytosol, muscle creatine kinase (MCK) reverses the reaction. It transfers the phosphate group from CP back to ADP, regenerating ATP.
This ATP can then be used for muscle contraction or other cellular activities.
The ADP produced from ATP consumption can then be reused in the mitochondria for another cycle of ATP production.
