Lipid Metabolism PDF

Lipid Metabolism BY HEBA MAREY LECTURER OF MEDICAL BIOCHEMISTRY FACULTY OF MEDICINE, MINIA UNIVERSITY  Digestion of Lipids Digestion of Triacylglycerols. Triacylglycerols are digested by a group of enzymes, they are: Lingual Lipase – It is secreted by Ebner...

Lipid Metabolism BY HEBA MAREY LECTURER OF MEDICAL BIOCHEMISTRY FACULTY OF MEDICINE, MINIA UNIVERSITY  Digestion of Lipids Digestion of Triacylglycerols. Triacylglycerols are digested by a group of enzymes, they are: Lingual Lipase – It is secreted by Ebner’s glands on the dorsal surface of the tongue. – It has minimal effect because food remains for a short time in the mouth. Gastric Lipase – Optimum pH for gastric lipase is 5.5 so it acts only in infant’s stomach (pH: 5) as it acts on milk fat.  Pancreatic lipase It is the most important lipase in the digestion of triacylglycerols. It removes the fatty acids at carbon 1 and 3 thus the primary products of hydrolysis are a mixture of 2-monoacylglycerol and free fatty acids The resulting 2-monoacylglycerols will undergo: 72 % are absorbed as such. 28 % are converted into 1-monoacylglycerols by isomerase enzyme which then: i) Absorbed as 1-monoacylglycerol (6 %). ii) Hydrolyzed by pancreatic lipase into glycerol and fatty acids (22 %) which are then absorbed.  STEATORRHEA Definition: It is a condition in which fat content of the stool is abnormally increased. Causes: Steatorrhea results from deficiency of any factor essential for digestion or absorption of lipids as : 1. Deficiency of pancreatic lipase. A- presence of undigested fat in stool B- No loss of fat-soluble vitamin 2. Deficiency of bile salts. A- presence of digested fat in stool B- Loss of fat-soluble vitamin 3. Defective cells of intestinal mucosa. Types of Body Lipids 1- Tissues lipid Present in cell membrane and brain, never oxidized to give energy by starvation 2- Depot Fat (adipose tissues) Sites 1- Under skin, breast 2- Around kidney 3- In omentum & mesentry Types 1- White adipose tissue Composed mainly of TAG 2- Brown adipose tissue Brown due to high content of blood supply and mitochondria. There are uncoupler protein called thermogenin, common in animal exposed to cold Function 1- Oxidation and give energy during starvation. 2- 7 dehydrocholsterol under skin give vitamin D3 3- Protect against cold. 4- Protect bony prominence. 5- Support kidney  Types of Body Lipids Depot fat Tissue fat 1- Nature Stored lipid Structural lipid 2- Type TG Phospholipids 3- Amount Variable Constant 4- starvation Decrease Constant 5- Fatty acid Saturated Unsaturated 6- Site skin, around kidney Cell wall, brain 7- Function Give energy Enter in structure  Lipolysis Lipolysis is carried out by three enzymes present in adipose tissue : 1. Hormone sensitive triacylglycerol lipase: 2. Diacylglycerol lipase. 3. Monoacylglycerol lipase Causes of Lipolysis: 1- Starvation, 2- Diabetes Mellitus 3- Low carbohydrate diet 4- Certain infectious disease as in tuberculosis (due to high catabolic state). Regulation of Lipolysis The key enzyme controlling lipolysis is Hormone sensitive triacylglycerol lipase (HS lipase): HS lipase present in 2 forms 1- Active form with phosphate 2- Inactive form without phosphate 1- Lipolytic factors: 1- Lipolytic hormone (anti-insulin hormone) - Epinephrine and norepinephrine - Glucagon - ACTH (adrenocorticotrophic hormone) - TSH (thyroid stimulating hormone) - Growth hormone 2- Methyl xanthine (caffeine) 3- Sympathetic nervous system 2- Anti lipolytic factors: - Insulin - Nicotinic acid and prostaglandin E.  Oxidation of Fatty Acid β Oxidation of fatty acid Site: occur in mitochondria of liver, never occur in brain Transport of fatty acids into mitochondria. After the fatty acid is taken up by the cell, it is converted to acyl CoA in the cytosol by fatty acyl CoA synthetase (thiokinase). Role of carnitine in β Oxidation of fatty acid (carnitine shuttle) Carnitine is carrier of FA from cytoplasm to mitochondria 1. Carnitine acyl transferase I: catalyzes transfer of a fatty acid from acyl CoA to carnitine to form acyl carnitine. 2. Carnitine Acylcarnitine translocase: mediates transmembrane exchange of fatty acyl-carnitine for carnitine. 3. Carnitine acyl transferase II: catalyzes transfer of the fatty acid from carnitine to coenzyme A. So, the acyl carnitine is reconverted to acyl-CoA and free carnitine in the mitochondrial matrix β- β-  Energy production of β-oxidation If palmitic acid (16 C) Net energy gain: [(16/2 – 1) X 5] + [(16/2) X 12] - 2 = [7 X 5] + [8 X 12] = (35 ATP + 96 ATP) – 2 ATP = 131 ATP – 2 ATP = 129 ATP. [No of cycles X 5 ATP] + [No of acetyl coA X 12 ATP] – 2 ATP Calculation formula of energy production for fatty acid oxidation : = (N/2 – 1) X 5 ATP) + (N/2 X 12 ATP) – 2 ATP where N represent number of carbon atoms of fatty acid. Importance of β-oxidation. 1. Energy production. 2. Production of acetyl CoA which enter in many pathways. 3. Ketone body formation : Acetoacetyl CoA is the last 4 carbon atoms in the course of β-oxidation it may be converted into acetoacetate; one of ketone bodies.  Source and fate of Acetyl coA Sources: A. Lipids: Oxidation of fatty acids and ketone bodies. B. Carbohydrate: Glucose oxidation → Pyruvate → Acetyl CoA. C. Proteins: 1. Ketogenic amino acids: Give directly acetyl CoA or indirectly give acetoacetate → Acetyl CoA. 2. Glucogenic amino acids → Pyruvate → Acetyl CoA. Fate: A. Oxidation: Through Krebs' (citric acid cycle). B. Lipogenesis: Formation of fatty acids and triacylglycerols. C. Ketogenesis: Synthesis of ketone bodies. D. Acetylcholine synthesis. E. Cholesterol synthesis: which is the precursor for: 1. Bile acids. 2. Vitamin D3. 3. Steroid hormones: glucocorticoids, mineralocorticoids, male sex hormones (testosterone) and female sex hormones (estrogens and progesterone).