lipids

• Triglycerides


  Fats and oils that are important dietary sources of energy
• Triglycerides


  • They are a major form of energy storage (9 Cal/g)
  • They are water-insoluble, so can be stored in larger quantities than carbohydrates
  • Carbohydrate reserves are depleted after about 1 day without food, but stored fat can provide needed calories for 30-40 days
• Digestion of Triglycerides


  1. Triglycerides are hydrolyzed to glycerol, fatty acids, and monoglycerides

  2. Phosphoglycerides are also hydrolyzed to their component substances (glycerol, fatty acids, phosphate groups, and aminoalcohols)

  
• Chylomicrons


  Lipoprotein aggregates that transport water-insoluble triglycerides, phosphoglycerides, and cholesterol in the lymph and bloodstream

  
• Concentration of plasma lipids

  Increases after a meal, then returns to normal as a result of storage in fat depots and oxidation to provide energy

  
• Lipoproteins

  Classified by density, with increasing lipid concentration making the lipoprotein less dense

  
• Types of lipoproteins


  • Chylomicrons
  • Very-low-density lipoproteins (VLDL)
  • Low-density lipoproteins (LDL)
  • High-density lipoproteins (HDL)

  
• Cholesterol


  Involved in the formation of cell membranes, the insulation of nerves, the synthesis of a number of hormones, and the digestion of food

  
• LDLs


  Transport cholesterol into the wall of an artery, causing the formation of plaques and leading to atherosclerosis
• HDLs


  Able to remove cholesterol from plaques in the arteries and transport it to the liver for excretion or reuse
• Resin drugs


  Bind with bile acids in the digestive tract and remove them from operation, causing the liver to synthesize more bile acids from cholesterol, so less cholesterol available to be released into the blood from LDL

  
• Lipid, or large doses of niacin

  Reduce the production of triglycerides, which are involved in the formation of LDL, so less cholesterol circulates in the blood

  
• Statins


  Block the synthesis of cholesterol in the liver by inhibiting HMG-CoA reductase, causing liver cells to remove cholesterol from the circulating blood; they also help the body to reabsorb cholesterol from plaque that has formed in blood vessels

  
• Carbohydrates from dietary sources and glycogen catabolism are used preferentially for energy production by some tissues, such as the brain and active skeletal muscles
• Body stores of glycogen are depleted after only a few hours of fasting, which requires fatty acids stored in triglycerides to be used as energy sources
• Even when glycogen supplies are adequate, resting muscle and liver cells use energy from triglycerides because this conserves glycogen stores and glucose for use by brain cells and red blood cells

  
• Brain cells do not obtain nutrients from blood
• Red blood cells do not have mitochondria, and cannot do fatty acid oxidation
• Fat mobilization


  The endocrine system produces hormones like epinephrine that interact with adipose tissue, stimulating the hydrolysis of triglycerides to fatty acids and glycerol, which enter the bloodstream

  
• Glycerol


  Water soluble, so it dissolves in the blood and is transported to cells that need it

  
• Glycerol metabolism


  Glycerol is converted to dihydroxyacetone phosphate in two steps, which is then converted to pyruvate and can contribute to cellular energy production or be converted to glucose through gluconeogenesis

  
• Fatty acid oxidation


  1. Fatty acids enter tissue cells and are converted into fatty acyl CoA by reaction with coenzyme A, with energy provided by ATP

  2. The fatty acyl CoA molecules then undergo β-oxidation in the mitochondria, where the second (beta) carbon away from the carbonyl group is oxidized to a ketone

  
• The complete conversion of a fatty acyl CoA to two carbon fragments of acetyl CoA always produces one more molecule of acetyl CoA than of FADH2 or NADH

  
• From one 18-C stearic acid molecule, 120 ATP's can be produced through the activation, β-oxidation, and entry into the citric acid cycle/electron transport chain

  
• β-oxidation of Fatty acids

  1. The complete conversion of a fatty acyl CoA to two carbon fragments of acetyl CoA

  2. Produces one FADH2, one NADH, and two acetyl CoA's

  
• The breakdown of 18-C stearic acid requires 8 passes through the spiral, and produces 9 acetyl CoA's, but only 8 FADH2's and 8 NADH's
• The Energy from Fatty Acids

  1. Activation of stearic acid by coenzyme A to form stearoyl CoA comes from the hydrolysis of 2 ATP's

  2. As a stearoyl CoA molecule (18 C's) passes through the β-oxidation spiral, 9 acetyl CoA's, 8 FADH2 's, and 8 NADH's are produced

  3. Acetyl CoA can enter the citric acid cycle / electron transport chain and form 10 ATP's

  4. Each FADH2 yields 1.5 ATP's

  5. Each NADH yields 2.5 ATP's

  6. From one 18-C stearic acid molecule, 120 molecules of ATP are formed

  
• Under normal conditions, most acetyl CoA produced during fatty acid metabolism is processed through the citric acid cycle


  During fasting, the balance between carbohydrate and fatty acid metabolism is lost, and fatty acids become the body's primary energy source
• During fasting


  • Minimal amounts of cellular glucose are available, the level of glycolysis decreases, and a reduced amount of oxaloacetate is synthesized
  • Oxaloacetate is also used for gluconeogenesis to a greater extent as the cells make their own glucose
  • The lack of oxaloacetate reduces the activity of the citric acid cycle, and acetyl CoA produced by fatty acid oxidation builds up faster than it can be processed by the citric acid cycle
• Ketone Bodies


  • Acetoacetate, β-hydroxybutyrate, and acetone
  • Carried by the blood to body tissues, mainly the brain, heart, and skeletal muscles, where they may be oxidized to meet energy needs
  • Under normal conditions, the concentration of ketone bodies in the blood averages 0.5 mg/100 mL

  
• Diabetes mellitus


  • Even though blood glucose reaches hyperglycemic levels, a deficiency of insulin prevents the glucose from entering tissue cells in sufficient amounts to meet cellular energy needs
  • This results in an increase in fatty acid metabolism, and the excessive production of acetyl CoA, and a substantial increase in the level of ketone bodies in the blood of untreated diabetics
• Ketonemia


  Concentration of ketone bodies higher than 20 mg / 100 mL of blood
• Ketonuria


  Ketone bodies are excreted in the urine when the renal threshold of about 70 mg/100 mL of blood is exceeded
• Ketosis


  Simultaneous existence of ketonemia, ketonuria, and acetone breath
• Ketoacidosis


  • Accumulation of acidic ketone bodies in the blood resulting in low blood pH
  • Leads to severe dehydration, general debilitation, coma, or death
• Fatty Acid Synthetase System

  1. Excess nutrients are converted to fatty acids, and then to body fat

  2. Fatty acid synthesis occurs in the cytoplasm rather than in the mitochondria

  3. Acetyl CoA is generated in the mitochondria, and transported to the cytoplasm for fatty acid synthesis in the form of citrate

  4. Fatty acid synthesis occurs in a complex series of reactions catalyzed by an complex called the fatty acid synthetase system

  
• The Synthesis of Palmitic Acid


  Requires a large input of energy in the form of 7 ATP's and 14 NADPH's
• Fatty Acids and the Liver

  • The liver is the most important organ involved in fatty acid and triglyceride synthesis
  • The only fatty acids that cannot be synthesized by the body are those that are polyunsaturated
  • Humans have no enzyme that catalyzes the conversion of acetyl CoA to pyruvate, which is required for gluconeogenesis