Ketone Bodies, Bile Salts and Cholesterol

β-Oxidation of Palmitic Acid

• Palmitic Acid (C16 Fatty Acid)

  • Performs 7 Cycles of β-oxidation.

  • Results in the formation of 7 Acetyl CoA.

    • Each Acetyl CoA yields 10 ATP.

  • Total ATP from Acetyl CoA: 70 ATP.

  • Production of 7 FADH2:

    • Each FADH2 yields 1.5 ATP.

    • Total from FADH2: 10.5 ATP.

  • Production of 7 NADH:

    • Each NADH yields 2.5 ATP.

    • Total from NADH: 17.5 ATP.

  • 1 Final Acetyl CoA: 10 ATP (from C4 breakdown).

  • Cost of forming fatty acyl CoA: -2 ATP.

  • Total Net Gain of ATP from Palmitic Acid: 106 ATP.

Production of Ketone Bodies

• Conditions for Ketone Body Production:

  • Increased energy requirements.

  • Limited dietary carbohydrates.

  • Glucose cannot be used for energy production.

• High rates of lipolysis and TCA cycle activity due to energy needs.

• Importance of Ketone Bodies:

  • By-products of fat oxidation when glucose oxidation decreases.

  • Serve as a crucial energy source for muscles and the brain during fasting or diabetic states.

  • Ketoacidosis occurs with excess ketone body production due to fatty acid breakdown.

• Substrates for Ketone Bodies:

  • Include Acetoacetate, Acetone, and β-hydroxybutyrate:

    • Only Acetoacetate and Acetone are true ketones; β-hydroxybutyrate lacks a keto group.

• Properties of Ketone Bodies:

  • Water-soluble and yield energy.

  • Normal blood concentration: < 3 mg/100ml.

Bile Salts

• Recycling of Bile Salts:

  • Production: Made in the liver from cholesterol.

  • Storage: Stored in the gallbladder.

  • Action: Act in the small intestine.

  • Reabsorption: Reabsorbed in the ileum (enterohepatic circulation).

  • Total Bile Pool: 2.5 – 5.0 g.

    • 90% reabsorbed.

    • ~ 0.5 g lost in feces per day.

    • Recycling of bile occurs about twice per meal.

• Effects of Soluble Fibers & Cholesterol-Lowering Drugs:

  • Soluble fibers bind to bile, leading to excretion.

  • Some drugs bind bile, promoting its excretion to lower blood cholesterol.

Cholesterol Synthesis

• Sources of Cholesterol:

  • Derived from glucose, fatty acids, and amino acids.

  • Dietary Recommendation: Less than 300 mg per day.

• Functions of Cholesterol:

  • Vital for bile synthesis in the liver.

  • Precursor for steroid hormones (estrogen, progesterone, androgen).

  • Component of cell membranes.

  • Precursor for Vitamin D.