lecture 3 principles of fats and oxidation processes

Principles of Fats and Oxidation Processes

• Fats tend to release water during complete oxidation.
    - Initial observations may suggest otherwise during beta oxidation and the citric acid cycle.
    - However, the electron transport chain facilitates significant water production from fatty acid molecules.

Beta Oxidation of Palmitic Acid

• Requires 1 molecule of water per cycle.

• Total of 7 cycles:
    - 7 molecules of water needed for the complete oxidation of palmitic acid.

Citric Acid Cycle

• Processes 8 acetyl CoA molecules.

• Each acetyl CoA requires 2 molecules of water per cycle.

• Total water input for citric acid cycle:
    - 8 acetyl CoA * 2 water = 16 molecules of water.

Summary of Water Requirement

• Total water in debt from beta oxidation and citric acid cycle:
    - 7 (beta oxidation) + 16 (citric acid cycle) = 23 molecules of water.

Electron Transport Chain Contribution

• Generates water from NADH and FADH2 produced:
    - 31 NADH and 15 FADH2 enters the electron transport chain.
    - Requires 23 molecules of oxygen for this process.
    - Produces:
       - 2 water for each oxygen consumed, resulting in 46 water molecules generated.

Final Water Balance

• Total water produced by electron transport chain: 46 molecules.

• Water deficit from oxidation processes: 23 molecules.

• Net production of water:
    - 46 (produced) - 23 (consumed) = 23 molecules of water.

Physiological Significance of Water Production

• Important for hibernating animals such as bears and marmots.
    - Bears hibernate for 4-5 months; marmots can hibernate for 6-8 months depending on snowfall.
    - During hibernation, water replacement from fat oxidation is crucial for hydration lost through respiration.

Comparison of Energy from Carbohydrates and Fats

• Focus on dodecanoic acid (lauric acid), a 12-carbon fatty acid:
    - Molecular weight: 200 grams per mole.
    - Energy yield:
      - Beta oxidation: 5 NADH and 5 FADH2, minus 2 ATP.
        - Produces 6 acetyl CoA.
      - Citric acid cycle: 18 NADH, 6 FADH2, and 6 ATP.
    - Total ATP from one mole of dodecanoic acid: 78 ATP.

Comparison with Glucose

• Glucose yields 32 ATP per 180 grams:
    - Approximate yield per gram:
      - Dodecanoic acid: $rac{78 ext{ ATP}}{200 ext{ g}} <br>ightarrow 0.39 ext{ moles of ATP per gram}$
      - Glucose: $rac{32 ext{ ATP}}{180 ext{ g}} <br>ightarrow 0.18 ext{ moles of ATP per gram}$.

• Actual weight of glucose in metabolism:
    - Glycogen has associated water, affecting the effective weight in calculations.
    - True weight considers additional water molecules bound to glucose residues.
      - For example, adding 1.5 molecules of water adjusts weight to 207 grams per mole.
    - This reduces glucose ATP yield further, enhancing fat’s efficiency for energy storage.

Odd-Chain Fatty Acids

• Rare yet present; sourced primarily from plants (e.g., waxes on fruits and leaves).

• Example: Wax from grape plants contains about 2% odd-chain fatty acids.

Mechanism of Oxidation

• Odd-numbered fatty acids produce a five-carbon intermediate and can yield:
    - A propionyl CoA through beta oxidation, which cannot undergo further beta oxidation directly.

• Propionyl CoA undergoes a series of metabolic conversions:
    - Carboxylation by propionyl CoA carboxylase (biotin-dependent) leading to methylmalonyl CoA.
    - Isomerization transforms methylmalonyl CoA into succinyl CoA (glucogenic).
      - Succinyl CoA participates in gluconeogenesis to generate glucose.

Enzymatic Mechanism

• Methylmalonyl CoA mutase (requires Vitamin B12/cobalamin) facilitates the rearrangement:
    - Genesis of a radical during the reaction stimulates the movement of carboxyl groups.
    - Cobalt in cobalamin cycles between oxidation states aiding the radical generation and subsequent transformations.

Production of Glucose from Odd-Chain Fatty Acids

• Example calculation:
    - Assume 1% of diet is odd-chain fatty acids.
      - 100 grams of fat contains approximately 1 gram of odd-chain fatty acids.
    - Average odd-chain fatty acid length of 19 carbons results in:
       - 8 acetyl CoA and 1 propionyl CoA from oxidation.
    - Estimated conversion:
       - Roughly 150 mg into propionyl CoA results in production of about 640 mg of glucose.
    - Notably, this amount is minor relative to daily glucose needs (+1 gram).

Limitations of Odd-Chain Fatty Acids in Glucose Production

• Odd-chain fatty acids from plants contribute insufficiently to replace glucose in the diet.
    - Require a substantial intake of carbohydrates (plant material) to generate the small amounts of glucose possible.

Peroxisomal Fatty Acid Oxidation

• Involved chiefly for fatty acids longer than 18 carbons, particularly notable in plants.

• Linked to the glyoxylate cycle, which plays a role in glucose production from fatty acids, significant during germination.

• Peroxisomes oxidize fats via:
    - Acyl CoA dehydrogenase transferring electrons to oxygen, producing hydrogen peroxide, leading to FAD reoxidation during oxidation.
    - Catalase decomposes the hydrogen peroxide, producing the namesake for peroxisomes.

Regulation of Fatty Acid Oxidation

• Controlled chiefly by energy demands and hormonal signals (glucagon vs. insulin).
    - Glucagon activates lipolysis and β-oxidation when glucose is low, enhancing fatty acids’ availability in muscle and liver cells.
    - Insulin decreases fatty acid availability, inhibiting fatty acid oxidation.

• Key regulatory enzymes include protein kinase A and AMP kinase, which inhibit fatty acid synthesis during energy demand.