Exam

Energy Metabolism

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Energy Metabolism, Energy Expenditure

  • See Also
  1. High Energy Molecule
  2. Protein Metabolism
  3. Lipid Metabolism
  4. Carbohydrate Metabolism
  5. Glucose Metabolism (Glycolysis, Gluconeogenesis)
  6. Disorders of Energy Metabolism
  7. Resting Energy Expenditure
  • Physiology
  • Energy Sources
  1. See Gastrointestinal Metabolism
  2. Background
    1. Ingested food is lysed into small component molecules for intestinal absorption
      1. Starches and Disaccharides are lysed into Monosaccharides
      2. Proteins are lysed into Amino Acids and some short-chain peptides
      3. Fats are lysed into free Fatty Acids and Cholesterol
    2. Intestinal epithelial cell absorption
      1. Simple diffusion (passive absorption) of free Fatty Acids, monoglycerides and water
      2. Active transport (esp. Sodium-Potassium ATPase pump) for most other molecules
    3. Portal circulation carries most absorbed energy sources to liver (except fats)
      1. Carbohydrates (the Monosaccharides Glucose, fructose and galactose)
      2. Proteins (Amino Acids and short-chain peptides)
      3. Short fatty-acids (remainder of fats are carried by Lymphatics)
    4. Lymphatics carry most absorbed fats
      1. Fats are carried by Chylomicrons via Lymphatics after intestinal absorption (see below)
    5. Malabsorption has many mechanisms
      1. Lactose Intolerance (Lactase Deficiency)
      2. Pernicious Anemia (Vitamin B12 Deficiency from Intrinsic Factor deficiency)
      3. Celiac Disease (gluten-mediated injury to intestinal villi)
    6. Energy sources by organ utilization
      1. Glucose
        1. Primary source of energy for most cells
      2. Ketones
        1. Secondary source of energy for the brain, heart and Muscle during starvation
      3. Fatty Acids
        1. Secondary source of energy in most cells during times of Hypoglycemia or starvation
        2. Fatty Acids do not cross the blood brain barrier (brain is unable to use Fatty Acids as fuel)
      4. Lactic Acid
        1. Liver uses Lactic Acid for energy after a meal
        2. Lactic Acid may fulfill energy demands in the brain (up to 70-75%) and heart (up to 20 to 25%)
  3. Carbohydrates (4 kcals/g)
    1. See Glucose Metabolism
    2. carbohydrateMetabolism.png
    3. Stores exhausted in first day of starvation
    4. Starches and Disaccharides are cleaved into Monosaccharides before intestinal absorption
      1. Mediated by Stomach acid and Salivary, intestinal and Pancreatic Enzymes (see below)
    5. Starches (Glucose polymers, cleaved by amylase into maltose)
      1. Glycogen
      2. Amylose
    6. Disaccharides
      1. Sucrose (Glucose+fructose, cleaved by sucrase)
      2. Lactose (Glucose+galactose, cleaved by lactase)
      3. Maltose (Glucose+Glucose, cleaved by maltase)
    7. Monosaccharides
      1. Glucose
      2. Fructose
      3. Galactose
  4. Protein (4 kcals/g)
    1. ProteinMetabolism.png
    2. Last to be catabolized in starvation
    3. Proteins are broken down to Amino Acids and some small peptides before absorption
      1. Mediated by Stomach acid, pepsin, trypsin and peptidases (see below)
    4. Proteins (polypeptides)
      1. Long chains of peptides (which in turn are chains of Amino Acids)
    5. Peptides
      1. Short chains of Amino Acids (two or more)
    6. Amino Acids
      1. Twenty common Amino Acids occur in humans, in which 9 are essential (must be ingested)
  5. Fat (9 kcals/g)
    1. See Fatty Acid
    2. See Cholesterol
    3. FatMetabolism.png
    4. Long term energy source
    5. Intestinal Digestion and Absorption of fats
      1. Duodenal bile salts emulsify fats into small droplets
      2. Enzymatic breakdown by intestinal and pancreatic agents
        1. Lipase (intestinal, pancreatic) lyse Triglycerides to monoglycerides and free Fatty Acids
        2. Esterases lyse Cholesterol to free Cholesterol and free Fatty Acids
        3. Phospholipases lyse phospholipids to free Fatty Acids and lysophospholipids
      3. Small micelles form from fat breakdown products and bile acids
      4. Micelles carry fats to intestinal epithelial cell brush border for absorption
        1. Bile salts allow for absorption of polar lipids
      5. Bile salts are reclaimed by enterohepatic circulation
        1. Bile salts absorbed in ileum are transported back to liver via portal circulation
    6. Intestinal Epithelial cell Processing of Fats
      1. Re-forming of lipids
        1. Triglycerides re-form from free Fatty Acids and monoglycerides
        2. Cholesterol esters re-form from free Fatty Acids and Cholesterol
        3. Phospholipids re-form from free Fatty Acids and lysophospholipids
      2. Chylomicrons
        1. Form from Apoproteins combined with Triglycerides, Cholesterol to phospholipids
        2. Chylomicrons move from intestinal epithelial cells into Lymphatic System
        3. Triglycerides are carried by Chylomicrons to Muscle and fat cells
          1. Triglycerides are lysed into free Fatty Acids by capillary LipoproteinLipase
          2. Free Fatty Acids are then absorbed by Muscle and fat cells
          3. Triglycerides reform from free Fatty Acids within Muscle and fat cells (esterification)
      3. Other Lipoproteins (VLDL, LDL, HDL)
        1. Form from Cholesterol processing in the liver
  1. See Glucose Metabolism
  2. See Fatty Acid
  3. Glycolysis (Embden-Meyerhoff Pathway)
    1. Glycolysis.png
    2. GlycolyticPathMolecules.png
    3. Catabolic pathway to breakdown Carbohydrates (Glucose, fructose) into pyruvate, without need for oxygen
    4. Represents only a small part of the overall energygeneration from Carbohydrates (2 net ATP and 1 NADH)
    5. Pyruvate may then be converted to Lactic Acid or acetyl-CoA (which enters TCA Cycle or is used to form Triglycerides)
    6. Triggered by Insulin, which lowers Glucose via both Glycolysis as well as increasing glycogen stores
  4. Citric Acid Cycle (Krebs Cycle, Tricarboxylic Acid Cycle, TCA Cycle)
    1. Glycolysis.png
    2. krebCycle.png
    3. electronTransportChain.png
    4. Universal pathway seen across multicellular organisms, taking place in mitochondria in humans
    5. Generates energy from Acetyl CoA (3 NADH, 1 FADH, 1 GTP) derived from Glucose, Amino Acids and Fatty Acids
    6. Intermediate steps include oxaloacetate, isocitrate, a-Ketoglutarate, succinyl-CoA, Succinate, fumarate, malate
  5. Gluconeogenesis
    1. gluconeogenesis.png
    2. Pathway forms Glucose from 3- or 4-carbon noncarbohydrate precursors (e.g. pyruvate, Amino Acids and Glycerol)
    3. Process takes place in the Kidneys and liver and is triggered when Insulin levels are low and in starvation states
    4. The same triggers for Gluconeogenesis also trigger Lipolysis and Ketogenesis
  1. See Fatty Acid
  2. FatMetabolism.png
  3. Fatty Acids are stored for later energy use, bound to Glycerol, as Triglycerides
    1. Insulin promotes Fatty Acid and Triglyceride synthesis (as well as that of glycogen and Proteins)
    2. Insulin promotes fat cell uptake of Glucose, which may be used to synthesize Fatty Acids
    3. Fatty Acids are synthesized by adding, in repeated cycles, 2 carbon atoms (from acetyl CoA) at a time
    4. Three Fatty Acid chains in turn, are bound to one Glycerol to form Triglycerides which are stored in fat cells
    5. Insulin reduces fat cell intracellular cAMP, thereby reducing Lipase activity (and Triglyceride breakdown)
  4. Fatty Acids are burned as fuel in the Kreb Cycle (TCA Cycle)
    1. Hypoglycemia triggers ephinephrine, Norepinephrine and Glucagon release
    2. Ephinephrine, Norepinephrine and Glucagon bind cell receptors, trigger cAMP to activate Lipase within fat cells
    3. Lipase breaks down Triglyceride into its Glycerol backbone and three Fatty Acid chains
    4. Fatty Acids are degraded (oxidized) by removing, in repeated cycles, 2 carbon atoms at a time (acetyl CoA)
    5. Glycerol may also enter Glycolysis (via Glycerol-3P to Dihydroxyacetone Phosphate to Glyceraldehyde-3P)
    6. Energy from each extracted acetyl coA enters the Kreb Cycle
    7. Each Kreb Cycle generates NADH and FADH2 (total energy 17 ATP per Fatty Acid chain)
  5. Fats offer high energy stores (9 KCals/g) compared with Carbohydrates and Proteins (4 kcals/g)
    1. Triglycerides are non-polar and bind less water (more compact than Carbohydrates, Proteins)
    2. Each triglcyeride contains 3 Fatty Acids, each with 16 to 18 carbons (fueling 24-27 Kreb Cycles)
    3. In addition, Glycerol, the Triglyceride backbone, may also fuel Glycolysis and the Kreb Cycle
  6. Fatty Acid Metabolism may also yield Ketones
    1. gluconeogenesis.png
    2. Fatty Acid chains are broken down into multiple acetyl-CoA molecules and a final acetoacetyl CoA
    3. Acetoacetyl CoA may be further broken down into acetyl-CoA for the Kreb Cycle or converted to Ketones
    4. Ketones include Acetoacetate, acetone and hydroxybutyrate
    5. Ketones may be used as fuel by the brain, heart and Muscle
    6. Ketones are typically generated at times of starvation or with Insulin deficiency (Diabetic Ketoacidosis)
  • References
  1. Goldberg (2001) Clinical Biochemistry, Medmaster, Miami, p. 4-23
  2. Guyton and Hall (2006) Medical Physiology, 7th Ed, Elsevier Saunders, Philadelphia, p. 829-58