Finals 2

• Lipids


  Large molecules, generally not soluble in water
• Lipid digestion


  • More complicated than carbohydrate digestion because most of our digestive tract and digestive enzymes are water-based
• Lipid digestion

  1. Lingual lipase and phospholipids initiate digestion

  2. Gastric lipases break down triglycerides

  3. Pancreatic lipase and bile salts break down triglycerides in small intestine

  4. Triglycerides recombined and form chylomicrons to enter lymphatic system
• Lipolysis


  Process of breaking down triglycerides via hydrolysis to fatty acids and glycerol
• Glycerol metabolism

  1. Glycerol enters bloodstream, converted to dihydroxyacetone phosphate in liver or kidney

  2. Dihydroxyacetone phosphate can be converted to pyruvate, acetyl CoA, or glucose
• Fatty acid oxidation


  1. Activated by binding to coenzyme A

  2. Transported to mitochondrial matrix

  3. Repeatedly oxidized to produce acetyl CoA, FADH2 and NADH
• Beta oxidation pathway

  • Oxidation (dehydrogenation)
  • Hydration
  • Oxidation (dehydrogenation)
  • Chain cleavage
• Acetyl CoA from fatty acid oxidation

  May enter citric acid cycle, form ketone bodies, or be used for fatty acid synthesis
• Ketone bodies


  Formed when acetyl CoA from fatty acid oxidation cannot be fully processed by the citric acid cycle
• Ketone bodies serve as fuel during prolonged fasting or uncontrolled diabetes when carbohydrate supply is low
• Glucose molecule

  6 carbon atoms
• Glucose molecule


  Produces 30 ATP molecules
• 3 molecules of glucose

  18 carbon atoms
• 3 molecules of glucose


  Produce 90 ATP
• Stearic acid molecule

  18 carbon atoms
• Stearic acid molecule


  Produces 122 ATP molecules
• Acetyl CoA


  Formed from fatty acid spiral, further processed by Citric Acid Cycle (Krebs Cycle)
• Adequate balance in carbohydrate and lipid metabolism


  Required
• Acetyl CoA

  Created from the oxidation of fatty acids and the krebs cycle is overloaded and cannot handle it, it is diverted to create ketone bodies
• Dietary intakes high in fat and low in carbohydrates

  Lipid-Carbohydrate Metabolism disturbed
• Diabetic conditions


  Glucose not used properly, Lipid-Carbohydrate Metabolism disturbed
• Ketone bodies


  Served as a fuel during prolonged fasting [or starvation or when patient suffer from uncontrolled diabetes] conditions under low supply of oxaloacetate the acetyl CoA will be in excess (increased concentration)
• Ketogenesis

  1. Condensation of 2 acetyl coa to form acetoacetyl CoA

  2. Acetoacetyl coa reacts with the third acetyl coa and water to produce 3-hydroxy-3-methylglutaryl CoA or HMG-CoA

  3. 3-hydroxy-3-methylglutaryl CoA or HMG-CoA is cleaved to acetyl CoA and acetoacetate

  4. Acetoacetate is reduced to B-hydroxybutyrate
• Ketone bodies

  Acetoacetic acid<|>B-hydroxybutyric acid<|>Acetone
• Ketonemia

  Blood
• Ketonuria


  Urine
• Acetone


  Product of ketone, one of the ketone bodies
• Lipogenesis

  1. Acetyl group of acetyl coa combines with oxaloacetate to form citrate

  2. Citrate transported from mitochondrial matrix to cytosol

  3. Citrate broken down into acetyl group and oxaloacetate

  4. Acetyl group joins coenzyme of cytosol forming acetyl coa

  5. Oxaloacetate reduced into NADH to Malate into the cytosol

  6. Malate transported into the matrix, oxidized by NAD to oxaloacetate
• Acetyl CoA


  Starting material for lipogenesis
• Citrate-malate transport system


  Helps transport Acetyl CoA to cytosol indirectly
• Acyl Carrier Proteins (ACP-SH)


  All intermediates in fatty acid synthesis are linked to
• Chain elongation

  1. Condensation: Acetyl-ACP and malonyl-ACP condense to form acetoacetyl-ACP

  2. Hydrogenation: Keto group of acetoacetyl complex reduced to alcohol by NADPH

  3. Dehydration: Water removed from alcohol to form alkene (Crotonyl ACP)

  4. Hydrogenation: Hydrogen added to alkene to form saturated butyryl ACP from NADPH
• Unsaturated fatty acid biosynthesis

  Requires oxidation and combines with hydrogen to remove water<|>Enzymes can only introduce double bond between C-4 and C-5 and between C-9 and C-10<|>Important essential unsaturated fatty acids linoleic and linolenic acid can't be synthesized, should come from diet
• Citric acid cycle intermediates

  Saturated C4 diacid -> Unsaturated C4 diacid -> hydroxy C4 diacid -> keto C4 diacid
• Lipogenesis C4 intermediates

  Keto C4 monoacid -> hydroxy C4 monoacid -> unsaturated C4 monoacid -> saturated C4 monoacid
• Cholesterol

  Secondary component of cell membrane<|>Precursor for bile salts, sex hormones, and adrenal hormone<|>Body synthesizes 1.5-2.0g everyday from acetyl CoA units<|>Average daily dietary intake is ~0.3g<|>Synthesis occurs in liver<|>Synthesis requires at least 15 acetyl CoAs and involves ~27 separate enzymatic steps
• Steroid hormones

  Cholesterol is converted to five major classes: progestins, androgens, estrogens, and Vitamin D
• Acetyl CoA


  • Primary link between lipid and carbohydrate metabolism
  • Starting material for biosynthesis of fatty acids, cholesterol and ketone bodies
  • Product of glucose, glycerol, and fatty acids
• Fates of Acetyl CoA


  • Oxidation in the citric acid cycle
  • Ketone body formation
  • Fatty acid biosynthesis
  • Cholesterol biosynthesis