Cellular Respiration, Fermentation, and Fuel Sources

Lactic Acid Fermentation

• Occurs when oxygen is limiting.
• Important for oxidizing other fuel sources like fatty acids and amino acids under aerobic or anaerobic conditions.

Recap of Cellular Respiration

• Oxidation of glucose (glucose catabolism).
• Catabolism: Breaking down larger molecules into smaller ones.
• Four major pathways:
  • Glycolysis:
    • Breaks down glucose (6-carbon molecule) into pyruvate (3-carbon molecule).
    • Occurs in the cytoplasm.
    • Produces a net of two ATP molecules.
    • $Glucose \rightarrow Pyruvate + 2\,ATP$
  • Intermediate Reaction:
    • Pyruvate is further oxidized to acetyl-CoA (2-carbon molecule).
  • Krebs Cycle:
    • Produces a small amount of ATP (2 ATP per glucose molecule).
  • Electron Transport Chain:
    • Produces a variable but significantly larger amount of ATP (28-34 ATP).

Oxygen Limiting Conditions

• Electron transport chain requires oxygen as the final electron acceptor.
• Occurs during strenuous exercise.
• Pyruvate from glycolysis undergoes lactic acid fermentation in the cytoplasm.
• End product: Lactate or lactic acid (depending on pH).
• Lactic acid accumulation may contribute to muscle soreness.
• Lactic acid fermentation doesn't directly produce ATP but is essential for glycolysis to continue.

Lactic Acid Fermentation in Detail

• Glucose undergoes glycolysis to produce pyruvate and a net of 2 ATP molecules.
• NAD (oxidized form) is reduced to NADH, carrying electrons to the electron transport chain.
• Maintaining the NAD/NADH ratio is crucial.
• Insufficient NAD slows down glycolysis.
• Electron transport chain typically regenerates NAD from NADH.
• Under oxygen-limiting conditions, lactic acid fermentation occurs:
  • $Pyruvate \rightarrow Lactate$
  • NADH is oxidized to NAD.
• Lactic acid fermentation replenishes NAD, allowing glycolysis to continue.
• Glycolysis is crucial when oxygen is limited, such as during intense exercise or when blood vessels are blocked.

Red Blood Cells

• Lack mitochondria.
• Rely solely on glycolysis and lactic acid fermentation for ATP production.
• Evolved this way to maximize hemoglobin content for oxygen transport.
• Reduced cell volume allows them to fit into capillaries.

Other Fuel Sources: Fatty Acids

• Long chains of hydrocarbons (hydrogen and carbon).
• Contain a carboxyl group (COOH).
• Have an even number of carbons.
• Oxidation occurs via beta oxidation.
• Most fatty acids come from triglycerides.
• Oxidation happens during starvation or fasting.
• Cardiac muscle utilizes fatty acids even at rest.
• Beta oxidation cleaves hydrocarbons two carbons at a time.
• Resulting two-carbon molecules resemble acetyl-CoA, which enters the Krebs cycle.

Fatty Acid Oxidation vs. Glucose Oxidation

• Depends on physiological state and tissue type.
• Brain prefers glucose, heart prefers fatty acids.
• Fatty acid oxidation takes longer due to larger molecule size.
• Requires more oxygen (five times more than glucose).
• Yields more ATP per molecule than glucose.
  • About 3 times higher ATP than in Glucose.
• Occurs only when oxygen is available.

Fatty Acids and Acetyl-CoA

• Fatty acids undergo beta-oxidation to form acetyl-CoA, which enters the Krebs cycle.
• Excess sugar can be converted to fatty acids and stored as triglycerides.
• Reactions are reversible.
• Triglycerides have three fatty acid chains, yielding many acetyl-CoA molecules.
• Limited capacity of the Krebs cycle leads to excess acetyl-CoA.

Ketone Bodies

• Excess acetyl-CoA is converted into ketone bodies (3-4 carbon molecules).
• Ketone bodies are a temporary form and can be reconverted to acetyl-CoA.
• The brain can use ketone bodies as fuel during starvation because they can cross the blood-brain barrier unlike fatty acids (glucose can also cross it).

Amino Acids

• Least preferred energy source; glucose and fatty acids are preferred.
• Glucogenic amino acids can be converted to pyruvate, then to glucose (gluconeogenesis).
• This occurs during prolonged fasting when glycogen stores are depleted.
• Some amino acids are both glucogenic and ketogenic.
• A small number are only ketogenic.
• Breakdown of amino acids occurs in the liver via deamination.

Deamination

• Amino acids have an amino group (nitrogenous portion - $NH_2$) and an acid group (non-nitrogenous portion with a carboxyl group - COOH).
• Side chain makes each amino acid unique.
• Deamination removes the nitrogenous portion to convert the amino acid into something resembling pyruvate or a ketone body.
• The amino group ($NH<em>2$) combines with hydrogen to form ammonia ($NH</em>3$), which is excreted as urea in the urine.
• The remaining carbon skeleton can be converted into a ketone body, pyruvate, or glucose.

Amino Acids and Energy Production

• Ketogenic amino acids are converted to ketone bodies and then acetyl-CoA.
• Glucogenic amino acids are converted to pyruvate and then glucose, which is important for glucose homeostasis, especially for the brain.

Nutrient Structures

• Carbohydrates: carbon, hydrogen, oxygen.
• Fats: mostly carbon and hydrogen.
• Amino acids: nitrogenous component and acid component.

Physiological States: Fed, Fasting, and Starvation

• Fed State: Up to 4 hours after a meal.
  • Excess glucose is stored in the liver as glycogen.
• Fasting State: 4-30 hours after a meal.
  • Glycogen is broken down to glucose to maintain glucose homeostasis.
  • Glucose prioritized for the brain and red blood cells.
  • The body may produce more glucose from amino acids through deamination.
  • Skeletal muscle at rest uses fatty acids predominantly (60-70%) but reduces glucose usage.
• Skeletal muscle: Primarily uses fatty acids at rest.

Tissue Preferences for Metabolic Sources

Brain Glucose Deprivation Symptoms

• Irritation.
• Hunger.
• Sweating.
• Blurry vision.
• Headaches.
• Ringing in the ears.
• Weakness.
• Fatigue.
• Anxiety.

Energy Usage by Organs

Brain uses the most energy in total, but the heart and kidneys use the most energy per unit of weight.

Starvation State

• 30+ hours after last meal.
• Rely on stored energy.

Energy Stores:

• Triglycerides (fat tissue): Largest energy reserve.
• Glucose/Glycogen: Limited storage.
• Mobilizable Proteins (muscle tissue): Can be used for energy in desperate need.

Fuel Usage During Starvation:

• The brain relies on ketone bodies from fatty acid oxidation in the liver.
• Breakdown of amino acids ramps up in the liver to form glucose (gluconeogenesis).

Ketone Bodies Beyond Starvation

• Also used post-exercise and by diabetics when target muscles can't take up glucose.
• Ketogenic diets involve high fat intake.

Ketoacidosis

• Excess ketone bodies make blood acidic (acidosis).
• Can occur in diabetics or during starvation (starvation ketoacidosis).