Fat Metabolism

Annotations:

• Fatty Acids are oxidised in the Mitocondria- 2 carbons removed to produce Acetyl Co-A---> Enters the Citric Acid Cycle.

1. Fed state
   1. Chylomicrons

      Annotations:

      • Assembled in the small intestine  and VLDL. Exported from the Liver. Bind to Lipo-Protein Lipase. (Lipo-Protein lipase catalyses hydrolysis of tri-acylglycerides and free fatty acids)
      • Released fatty acids enter the cells. Some remain in blood stream and taken up by the liver to be re-esterified and exported in VLDL
2. Fasted State
   1. Tri-acylglycerols

      Annotations:

      • Hydrolysis of Tri-acylglycerols catalysed by hormone sensitive Lipase to release free fatty acids into the blood stream- to bind with albumin and be transported to tissues. Hormone sensitive Lipase released from adipose tissue in response to a falling Insulin or adrenaline secretion.
3. Glycerol

   Annotations:

   • Released by Lipase or Lipo-protein lipase. Mainly transported to the liver and used as a metabolic fuel or for glucogenesis 
4. Factors affecting Fatty Acid Synthesis
   1. Insulin-STIMULATES
   2. Glucagon-REDUCES

1. Fasting State

   Annotations:

   • Tissues cannot meet energy requirements from Fatty Acids alone. The Liver forms more Acetyl-CoA from fatty acids. Synthesizes Ketone bodes and exports them to other tissues for use as a metabolic fuel
2. Acetoacetate

   Annotations:

   • Chemically Unstable --> Yields acetone which is poorly metabolized, it is mainly secreted through Urine or exhaled air. To avoid secretion of this fuel. Most Acetoacetate is reduced to B-Hydroxybuterate before being released from the liver. Acetoacetate utilization is regulated by the citric acid cycle.
3. B-Hydroxybuterate
4. Acetone
5. High Blood concentration = Ketosis
   1. Metabolic Acidosis

1. Fed State

   Annotations:

   • Substrates are converted into storage compounds to be used in the fasting state
   1. Tri-acylglycerols

      Annotations:

      • In Adipose tissue
   2. Glycogen

      Annotations:

      • In the Liver and Muscle
2. Fasting State

   Annotations:

   • Reserves are metabolized and used Glucagon forms Glucose. Increased supple of Amino Acids from protein for glucogenesis; due to faster catabolism of protein than synthesis
   1. Adipose Tissue reserves Fatty Acids and Glycerol
   2. Glycogen forms Glucose

1. B-Oxidation occurs in Mitocondrial Matrix
2. Fatty Acid synthesis occurs in the Cytosol
3. Acetyl-CoA derived from Pantenoic acid & Cysteamine
4. Triacylglycerols

   Annotations:

   • Lipid found in Adipose tissue. Synthesis in small intestine, lives, adipose tissue, lactating mammary glands and skeletal muscle.
   1. Synthesis in adipose tissue from Fatty Acids & Packed into Chylomicrons

1. Takes up Fatty Acids from Chylomicrons and VLDL
2. Tri-acylglycerols are synthesized from dietary fatty acids and packages to Chylomicrons

1. VLDL

   Annotations:

   • Assembled in the liver. Contain Triacylclycerols, cholesterol and cholesterol/esters and lipids from chylomicron remnants. VLDL are gradually depleted of lipids forming IDL. 
2. IDL

   Annotations:

   • IDL take up cholesterol esters to form LDL
3. Chylomicrons

   Annotations:

   • Least dense Formed in the intestinal mucosa. Circulate as a source of Tri-acylglycerols in the fed state --->Packages into Chylomicrons which appear in blood stream 60 mins after fatty meal Chylomicron remnants are cleared by the liver
4. LDL

   Annotations:

   • LDL receptor synthesis is repressed by Cholesterol. Less LDL will be cleared from the Liver. High LDL and Cholesterol major factor in development of athersclorosis and ischaemic heart disease.
   1. High Levels
      1. Increased Synthesis & Secretion of VLDL
      2. Decreased LDL clearance
      3. Not Cleared ---> Lipid Engorged Macrophages--->Necrosis of blood vessel endothelium = Atherosclerotic Plaque
5. HDL

   Annotations:

   • Surplus cholesterol exported Via HDL. Return to liver for excretion and catabolism. HDL secreted from Liver as a lipid poor protein and takes up cholesterol from tissues by enzymatic action.

1. Fed State = Glycogen synthesised from glucose in both liver and muscle
2. Fasted State = Glycogen is broken down by the removal of glucose units