Downloaded 426 times
Uploaded byshivaakumar
Triglyceride metabolism
The document discusses lipids and triglycerides, explaining that triglycerides are composed of a glycerol molecule bonded to three fatty acids and serve as the main form of energy storage. It describes the processes of lipogenesis where triglycerides are synthesized from glucose, and lipolysis where triglycerides are broken down by hormones to release fatty acids. The summary also notes that triglycerides are stored in adipose tissue and mobilized from there to meet energy needs or deposited in the liver in conditions like fatty liver disease.
In this document
Powered by AI
Dr. J. Sivakumar introduces lipids, describing their properties and categorizing them into triglycerides, phospholipids, and steroids.
Detailing triglycerides' composition from glycerol and fatty acids, focusing on structural aspects and variations in fatty acids.
Discusses the nature of vegetable oils, energy yield, and their significance in various tissues and states (like resting skeletal muscle and migratory birds).
Explains how triglycerides and cholesterol are transported in lipoproteins and the synthesis processes in liver and adipose tissue.
Outlines the metabolic pathways for glycerol synthesis, focusing on glucose metabolism and DHAP in adipose tissue.
Illustrates TAG hydrolysis by pancreatic lipase, emphasizing co-lipase role and the reactivity of TAG in adipose tissues.
Details the hormonal regulation of TAG mobilization during fasting, discussing lipolytic effects of glucagon and epinephrine.
Explores diabetes' impact on fatty acid mobilization and TAG overproduction, linking obesity with insulin resistance.
Identifies and compares white and brown adipose tissues, focusing on storage and thermogenesis roles.
Explains thermogenesis in brown adipose tissue, detailing its metabolic processes and liver's role in TAG transport.
Describes fatty liver disease, its causes—including alcoholism, toxic injury, and dietary factors—and protective substances like choline and Omega-3.
More Related Content
Similar to Triglyceride metabolism
Triglyceride metabolism
- 1.
- 2. Lipids havea varied structure but all have the following properties in common:- Insoluble in water Soluble in organic solvents The three main groups of lipids are:- Triglycerides Phospholipids Steroids
- 3. Triglycerides consist ofa single glycerol molecule and three fatty acids. Triglycerides form by condensation (dehydration) reactions between the hydroxyl (OH) groups of the glycerol and the carboxyl (COOH) group of three fatty acids. Triglycerides are esters being derived from an alcohol and a fat
- 4. Glycerol (blue)is an alcohol derivative of glyceraldehyde and has three hydroxyl groups. It acts as the backbone of the structure. Fatty acids (red) – there are more than 70 types of fatty acid but they all have long hydrocarbon tails and a terminal carboxyl group (COOH). The variety of fatty acids determine the properties of each triglyceride.
- 5. Vegetable oilsare triglycerides that are liquid at room temperature due to their higher unsaturated or shorter-chain fatty acids. Natural fats have D-configuration Usually R1 and R3 are saturated and R2 is unsaturated Natural fats are mixture of two or more simple triglycerides
- 6. Stored inanhydrous state Non-polar Provide ~ 6 times energy of hydrated glycogen ◦ Stored in large quantities in cells Non-reactive with other cell components Segregated into lipid droplets Do not affect osmolarity of cytosol
- 7. Triglycerides arealso the major form of stored energy in the body Hormones (glucagon, epinephrine, ACTH) trigger the release of fatty acids from adipose tissue.
- 8. Used for >half the energy in: Liver Heart Resting skeletal muscle Hibernating animals and migrating birds Higher plants: Do not depend on fats for energy Germinating seeds
- 9. • Cholesterol, Triglyceridesand Phospholipids • Transported by lipoproteins • Cholesterol can be free or esterified • Triglycerides must be degraded to be absorbed by cells
- 10. Liver andadipose tissue are the major sites of triacylglycerol (TAG) synthesis. The TAG synthesis in adipose tissue is for storage of energy whereas in liver it is mainly secreted as VLDL and is transported. The TAG is synthesized by esterification of fatty acyl CoA with either glycerol-3- phosphate or dihydroxy acetone phosphate (DHAP).
- 11. The glycerolpart of the fat is derived from the metabolism of glucose. DHAP is an intermediate of glycolysis. Glycerol-3-phosphate may be formed by phosphorylation of glycerol or by reduction of dihydroxy acetone phosphate (DHAP)
- 12. In adiposetissue, glycerol kinase is deficient and the major source is DHAP derived from glycolysis. In liver, glycerol kinase is active. The fatty acylCoA molecules transfer the fatty acid to the hydroxyl groups of glycerol by specific acyltransferases.
- 13. In additionto these two pathways, in the intestinal mucosal cells the TAG synthesis occurs by the MAG pathway. The 2-MAG absorbed is re-esterified with fatty acylCoA to form TAG.
- 14. Under conditionsof fasting, it is seen that synthesis of triacylglycerol occurs side by side with lipolysis, since the free fatty acid level is high in plasma. In the fasting state, the glycerol phosphate is derived from dihydroxyacetone phosphate formed during gluconeogenesis.
- 15. The activityof the enzyme PEPCK is enhanced in liver and adipose tissue during conditions of fasting, so that glycerol phosphate is available to esterify and store the excess fatty acid mobilized.
- 16. Esterification offatty acylCoA with glycerol phosphate to form triacylglycerol occurs at a rapid rate during the fed state. The glycerol phosphate is derived from the metabolism of glucose in the fed state by channeling dihydroxy acetone phosphate, an intermediate of glycolysis.
- 17. Pancreatic lipasecan easily hydrolyze the fatty acids esterified to the 1st and 3rd carbon atoms of glycerol forming 2- monoacylglycerol and two molecules of fatty acid. Then an isomerase shifts the ester bond from position 2 to 1. The bond in the 1st position is then hydrolyzed by the lipase to form free glycerol and fatty acid
- 19. The bindingof co-lipase to the triacylglycerol molecules at the oil water interface is obligatory for the action of lipase. The co-lipase is secreted by the pancreas as an inactive zymogen (molecular weight 11,000). It is activated by trypsin.
- 20. The adiposetissue serves as a storage site for excess calories ingested. The triglycerides stored in the adipose tissue are not inert. They undergo a daily turnover with new triacylglycerol molecules being synthesized and a definite fraction being broken down.
- 21. The dietarytriglycerides transported by chylomicrons and the endogenously synthesized triglycerides from liver brought by VLDL are both taken up by adipose tissue and esterified and stored as TAG. The lipoprotein molecules are broken down by the lipoprotein lipase present on the capillary wall.
- 22. In wellfed condition, glucose and insulin levels are increased. GluT4 in adipose tissue is insulin dependent. Insulin increases the activity of key glycolytic enzymes as well as pyruvate dehydrogenase, acetyl CoA carboxylase and glycerol phosphate acyl transferase. The stimulant effect of insulin on the uptake of glucose by adipose tissue, on the glycolysis and on the utilization of glucose by HMP pathway also enhances lipogenesis
- 23. Insulin alsocauses inhibition of hormone sensitive lipase, and so lipolysis is decreased
- 24. TAG fromthe adipose tissue is mobilized under the effect of the hormones, glucagon and epinephrine. The cyclic AMP mediated activation cascade enhances the intracellular hormone sensitive lipase. The phosphorylated form of the enzyme is active, which acts on TAG and liberates fatty acids.
- 25. Under conditionsof starvation, a high glucagon, ACTH, glucocorticoids and thyroxine have lipolytic effect. The released free fatty acids (FFA) are taken up by peripheral tissues as a fuel.
- 26. Lipolysis isenhanced and high FFA level in plasma is noticed in diabetes mellitus. Insulin acts through receptors on the cell surface of adipocytes. These receptors are decreased, leading to insulin insensitivity in diabetes.
- 27. Increased mobilizationof fatty acids from adipose tissue and the persistently high free fatty acid levels in the presence of hyperinsulinemia stimulates synthesis of triacylglycerol. The overproduction of TAG leads to increased release of VLDL from liver causing hypertriglyceridemia
- 28. The fatcontent of the adipose tissue can increase to unlimited amounts, depending on the amount of excess calories taken in. This leads to obesity. A high level of plasma insulin level is noticed. But the insulin receptors are decreased and there is peripheral resistance against insulin action.
- 29. There aretwo types White adipose tissue Brown adipose tissue
- 30. It ismainly concerned with energy storage. It is made up of spherical cells, with very few mitochondria. The triglycerides form the major component of white adipose tissue (about 80%) with oleic acid being the most abundant fatty acid (50%).
- 31. Brown adiposetissue is involved in thermogenesis. Brown adipose tissue cells are polygonal with more abundant cytoplasm. The brown color is due to the presence of numerous mitochondria. It is primarily important in new born human beings and adult hibernating animals.
- 32. Thermogenesis isa process found in brown adipose tissue. It liberates heat by uncoupling oxidation from phosphorylation. So energy is released as heat, instead of trapping it in the high energy bonds of ATP by the action of the uncoupling protein, thermogenin.
- 33. Liver producesfatty acid and TAG (triacylglycerol), which is transported as VLDL (very low density lipoprotein) in the blood. The fatty acids from VLDL are taken up by adipose tissue with the help of lipoprotein lipase, and stored as TAG. This neutral fat is hydrolysed by hormone sensitive lipase into NEFA, which in the blood is carried by albumin. The NEFA is utilized by the peripheral tissues, excess of which can be taken up by liver cells. Thus there is a constant flux of fat molecules from liver to adipose tissue and back
- 34. Fatty liverrefers to the deposition of excess triglycerides in the liver cells. The balance between the factors causing fat deposition in liver versus factors causing removal of fat from liver, determines the outcome.
- 35. Causes offat deposition in liver 1. Mobilization of NEFA from adipose tissue. 2. More synthesis of fatty acid from glucose. Reduced removal of fat from liver 3. Toxic injury to liver. Secretion of VLDL needs synthesis of apo B-100 and apo C. 4. Decreased oxidation of fat by hepatic cells.
- 36. Excessive Mobilization ofFat Excess Calorie Intake Toxic Injury to Liver Alcoholism
- 37. Non-alcoholic fattyliver disease (NAFLD) is the most common liver disease, where fat accumulates in hepatocytes. High fat diet and uncontrolled diabetes mellitus are the most common causes. As it is progressed, inflammatory reaction occurs, which is then termed as nonalcoholic steatohepatitis (NASH).
- 38. Fat moleculesinfiltrate the cytoplasm of the cell (fatty infiltration). These are seen as fat droplets, which are merged together so that most of the cytoplasm becomes laden with fat. The nucleus is pushed to a side of the cell, nucleus further disintegrated (karyorrhexis), and ultimately the hepatic cell is lysed. As a healing process, fibrous tissue is laid down, causing fibrosis of liver, otherwise known as cirrhosis. Liver function tests will show abnormal values.
- 39. They arerequired for the normal mobilization of fat from liver. Therefore deficiency of these factors may result in fatty liver. They can afford protection against the development of fatty liver. Choline: Feeding of choline has been able to reverse fatty changes in animals. Lecithin and methionine. They help in synthesis of apoprotein and choline formation. The deficiency of methyl groups for carnitine synthesis may also hinder fatty acid oxidation.
- 40. Vitamin Eand selenium give protection due to their antioxidant effect. Omega-3 fatty acids present in marine oils have a protective effect against fatty liver.