Lipids Metabolism Dr. Shaimaa - PowerPoint Presentation

1. Lipids MetabolismDr. Shaimaa Munther

2. LipidsLipids are compounds that are insoluble in water, but soluble in an organic solvent (e.g., ether, benzene, acetone, chloroform)“lipid” composed mainly from C, H, O • The main feature, in all lipids, is the large number of carbon-hydrogen bonds which makes them non-polar.

3. Lipid Classification

4. LIPID DIGESTIONTypical high-fat meals contain gram-level amounts o f triglycerides and milligram level amounts of cholesterol and cholesterol esters. Upon entry into the intestinal lumen, bile is secreted by the liver to emulsify the lipid contents. The pancreas secretes pancreatic lipase, colipase, and cholesterol esterase that degrade the lipids to 2-monoglyceride, fatty acids, and cholesterol.These lipids are absorbed and re-esterified to triglycerides and cholesterol esters and packaged, along with apoprotein B-48 and other lipids (e.g., fat-soluble vitamins), into chylomicrons.Normally, there is very little lipid loss in stools. Defects in lipid digestion result in steatorrhea, in which there is an excessive amount of lipids in stool (fatty stools).

5. Transport and storage of fatty acids and triacylglycerols

6. Lipid TransportLipid Transport as lipoproteins, which are clusters of lipids and proteins that are used as transport vehicles for fat, 4 main classes are present:ChylomicronsVLDL = very low density lipoproteinsLDL = low density lipoproteinsHDL = high density lipoproteinsFree fatty acids are attached to albumin and transported through blood

7. Lipoproteins are molecules that interact with water insoluble fat molecules, and transports those fats in the plasmaThe textbook describes the lipoproteins as “oil tankers” Different lipoproteins are responsible for the transportation of different fatsLipoproteins allow fat to be dissolved into the plasma7What are lipoproteins and why do we need them?

8. Lipids are transported through physiological fluids as a lipoprotein complex . These are spherical particles:– Core: relatively non-polarTriglyceridesCholesterol esters– Surface: relatively polarPhospholipidsProteinscholesterolLipoproteins

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10. Lipoproteins contain one or more specific proteins called apolipoproteins located near the surfaceApolipoproteins have specific functions:– Activate metabolic enzymes– Maintain structural integrity of lipoprotein– Facilitate uptake of lipoprotein into cellsResearch indicates apolipoprotein abnormalities may lead to abnormal lipid metabolism and metabolic disorders such as:– Atherosclerosis– Cardiovascular disease– Stroke– Alzheimer’s diseaseLipoproteins

11. There are 4 types of lipoproteinsChylomicronsTransport of dietary triglycerides ( exogenous TG) from the GI tract to the liverVery Low Density Lipoproteins ( VLDL )Transport of synthesized triglycerides ( Endogenous TG) from the liver to tissues for storage and energyLow Density Lipoproteins ( LDL ) Transports cholesterol to peripheral tissuesHigh Density Lipoproteins ( HDL )Transports cholesterol away from the peripheral tissues to the liver11lipoproteins

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13. Lipoprotein Metabolism

14. Lipid MetabolismThis includes lipogenesis and lipolysis , the most important to be studied are the pathways concerned with triglycerides and cholesterol metabolisms: Reserves of stored triglycerides are mobilized as needed for energy production. Fat mobilization is stimulated by epinephrine. The triglycerides are hydrolyzed to fatty acids and glycerol and enter the blood stream. Glycerol is converted to glycerol- 3 phosphate and then to dihydroxyacetone phospahte, which enters glycolysis for energy production. Free fatty acids are converted to fatty acyl CoA molecules, which are broken down to acetyl CoA by beta oxidation. The acetyl CoA may be used for energy production by way of the citric acid cycle and the electron transport chain.Cholesterol is needed by almost all cells and is precursor for hormones and bile acids .

15. DE NOVO SYNTHESIS OF FATTY ACIDSA large proportion of the fatty acids used by the body is supplied by the diet. Carbohydrates and protein obtained from the diet in excess of the body’s needs for these compounds can be converted to fatty acids, which are stored as triacylglycerols. In adult humans, fatty acid synthesis occurs primarily in the liver and lactating mammary glands and, to a lesser extent, in adipose tissue. This cytosolic process incorporates carbons from acetyl coenzyme A (CoA) into the growing fatty acid chain, using adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH).

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17. MOBILIZATION OF STORED FATS AND OXIDATIONOF FATTY ACIDSFatty acids stored in adipose tissue, in the form of neutral TAG, serve as the body’s major fuel storage reserve. TAGs provide concentrated stores of metabolic energy because they are highly reduced and largely anhydrous. The yield from the complete oxidation of fatty acids to CO2 and H2O is 9 kcal/g fat (as compared to 4 kcal/g protein or carbohydrate).

18. Fatty Acid OxidationFatty acids are degraded to acetyl CoA the process called β-oxidation Fatty acids enter tissue cells in need of energy. Fatty acids must pass through the mitochondrial membrane to be oxidized and to produce energy. The passage cannot occur until the fatty acid is converted to its thioester with CoA. The product of this reaction is fatty acyl CoA. The reaction is: Fatty acid + HS – CoA + ATP Fatty acyl CoA + AMP + PiThis is known as activation of fatty acid. Fatty acids must be activated before they are degraded to produce energy. Fatty acids are activated in the cytosol, but oxidation occurs in the mitochondria.

19. -oxidation is the mitochondrial process by which fatty acids are oxidized to yield NADH, FADH2, and acetyl-CoA. Ketogenesis takes place in liver mitochondria when acetyl-CoA levels are high and oxaloacetate levels are low. Key Concepts in Lipid catabolism

20. Beta oxidationThe formation of fatty acyl CoA molecule prepares fatty acids for entry into the mitochondria. Carnitine helps fatty acly CoA to enter mitochondria. There they are degraded in the catabolic process called beta oxidation. During beta oxidation, the third (or beta) carbon of the saturated fatty acid chain of the fatty acyl CoA is oxidized to a ketone.Beta oxidation is a spiral pathway. Each round consists of four enzyme-catalyzed steps that yield one molecule of acetyl CoA and an acylCoA shortened by two carbons, which becomes the starting substrate for the next round. Seven rounds of beta oxidation degrade a C16 fatty acid to eight molecules of acetyl CoA.Complete oxidation of one molecule of palmitic acid to carbon dioxide and water yields 129 molecules of ATP. One round of beta oxidation yields 17 ATP. Beta Oxidation is regulated by availability of free CoA, by the ratios of NAD/NADH and Q2.

21. -oxidation yields large amounts of ATPThe energy conversion process of fatty acid --> ATP involves oxidation of fatty acids by sequential degradation of C2 units leading to the generation FADH2, NADH, and acetyl CoA. The subsequent oxidation of these reaction products by the citrate cycle and oxidative phosphorylation generates lots of ATP. Palmitate(C16)

22. KetogenesisKetogenesis (synthesis of ketone bodies) takes place primarily in the liver. When fatty acid oxidation produces more acetyl-CoA than can be combined with Oxaloacetate to form citrate, then the "extra" acetyl-CoA is converted to acetoacetyl-CoA and ketone bodies.Keton bodies includes : acetoacetate , aceton & β- hydroxy butric acid Acetyl-CoA derived from fatty acid oxidation enters the Citrate Cycle only if carbohydrate metabolism is properly balanced.

23. Cholesterol synthesisSynthesis of cholesterol takes place in cytosol.The carbon skeleton of cholesterol is formed from acetyl CoA. The pathway of cholesterol biosynthesis has over 30 steps.The rate determining step of cholesterol synthesis and the major control point is the conversion of hydroxy methyl glutarate – co A (HMG-COA) to mevolonic acid.Some intermediate steps of cholesterol synthesis are mevolonic acid— squalene— zymosterol—cholesterol.

24. The fate of cholesterolIt can be incorporated into a cell membrane.It may be acylated to form cholesteryl ester for storage.It is precursor of steroid hormone (estrogen, testosterone)It is a precursor of bile acids.

25. Summary of lipid metabolism

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