Lipid Metabolism Lecture Notes PDF

Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Biochemistry 11, MLS 257 IVY OFORI BOADU Department of Medical diagnostics FAHS, KNUST, Kumasi 1/19/24 I BOADU ...

Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Biochemistry 11, MLS 257 IVY OFORI BOADU Department of Medical diagnostics FAHS, KNUST, Kumasi 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Course Objectives At the end of the course, the student will be able to; Explain the processes involved selected metabolic pathways such as lipid metabolism and cholesterol synthesis. Describe the functions of bile salts and its application in lipid metabolism Discuss the principles involved in protein degradation and nitrogen balance and its attendant metabolic diseases. Discuss the mechanisms that leads to oxygen toxicity and oxidative stress. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Lipid metabolism IVY OFORI BOADU,MLS, (PhD), FWAPCMLS Department of Medical diagnostics FAHS, KNUST, Kumasi 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Lipid metabolism- includes synthesis and degradation of fatty acids and /oe more complex lipids Liver and pancreas play are important sites for lipid metabolism and play an importantb role in the process of lipid digestion, absorption,synthesis, decomposition and transport. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana LIPIDS- OVERVIEW Lipds- Greek word, lipos, meaning FATS lipids are an organic substance found in living systems that is insoluble (hydrophobic) in water but is soluble (hydrophilic) in organic solvents. Lipids vary widely in their structures. composed of mostly carbon-hydrogen (C-H) attached to carboxyl group. Hydrophobic nature Compartmentalized.(membrane associated lipids) droplets of triglycerides in adipocytes (transport bound to protein) 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana vLipids and lipoproteins, which are central to the energy metabolism of the body, have become increasingly important in clinical practice, primarily because of their association with coronary heart disease (CHD). vLipids are a heterogenous class of naturally occurring compounds classified together based on common solubility properties. vThere are relatively insoluble in water but freely soluble in nonpolar organic solvents like acetone alcohol and ether 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana classification 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Functions of body lipids Major source of energy for the body, Provide the hydrophobic barrier that permits partitioning of the aqueous contents of cells and subcellular structures. Lipids serve additional functions in the body (for example, some fat- soluble vitamins have REGULATORY or COENZYME functions. HOMEOSTASIS - prostaglandins and steroid hormones play major roles in the control of the body’s homeostasis). Deficiencies leads to major clinical conditions such as arteriosclerosis, diabetes, dyslipidemia, obesity. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Functions of body lipids As important signaling molecules Molecules that binds specifically to other molecules Oxidation of lipids produced more energy than the oxidation of carbohydrates Humans have fat tissue under the skin, in the abdominal cavity, and in the mammary gland 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Nomenclature of lipids qShort hand nomenclature describes total number of carbons, double bonds and the position of the double bond(s) in the HC tail. q C18:1 Δ9 = oleic acid, 18 carbon fatty acid with a double bond positioned at the ninth carbon counting from and including the carboxyl carbon (between carbons 9 and 10) C C C10 C12 C14 16 18 O C4 C6 C8 C17 C2 C11 C13 C15 C5 C7 C9 C1 C3 HO qOmega (Ѡ) notation – counts carbons from end of HC chain. qOmega 3 fatty acids advertised as health promoting qLinoleate = 18:3 Δ9,12,15 andO 18:3Ѡ3,6,9 C C C C 10 12 C14 C16 C18 C2 C4 6 8 C13 C C17 C7 C9 C11 C1 C3 C5 H15 1/19/24 I BOADU HO  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Image of cis and trans formation When the two hydrogen atoms stick out on the same side of the chain, the fatty acid is said to be in a cis configuration The more double bonds in the cis configuration, the less flexible is the fatty acid. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Sources of fats for Metabolism Dietary fats Fat stores in adipose tissues Fat synthesized from excess carbohydrates 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana INTRODUCTION - Dietary FATS Fats and oils- make up 95% of the nutritional lipids Fats-are solid triglycerides Oils are liquid triglycerides Steriods and waxes – 5% 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Dietary composition of lipids We ingest about 100g of lipids daily More than 90% triglycerides Others Cholesterol Cholesteryl esters Phospholipids free fatty acids 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Dietary source of lipids 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Dietary source of lipids Animal sources Diary products-meat, butter , cheese, milk eggs, fish , pork, poultry Plant sources Cooking oils, nuts, seed, avocados 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana LIPID DIGESTION Digestion in the mouth Secretion of enzyme, lingual lipase, LIGUAL LIPASE Secreted by dorsal surface of tongue Active at low Ph (2.0-7.5) Ideal substrate – short chain TG Milk fat contains short chain TG which are esterified at 3- position, thus best substrate for lingual lipase. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana LIPID DIGESTION Digestion in the stomach Gastric lipase- secreted in small quantities Not effective for long chain fatty acids, mostly for short to medium chain FFAs Milk , egg yolk and fats containing short chain are the suitable substrate These lipases” (lingual and gastric) play a particularly important role in lipid digestion in neonates, for whom milk fat is the primary source of calories. They also become important digestive enzymes in individuals with pancreatic insufficiency such as those with cystic fibrosis (CF). 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana LIPID DIGESTION DIGESTION IN SMALL INTESTINE ØMajor site for fat digestion ØEffective digestion due to the presence of pancreatic lipase and bile salts ØBile salts act as effective emulsifying agent for fats ØSecretion of pancreatic juices , stimulated by Ø Passage of acidic gastric content into the duodenum Ø Secretion of secretin, cholecystokinin. (CCK) 1/19/24 I BOADU  Kwame Nkrumah University of Control of Digestion Science & Technology, Kumasi, Ghana Pancreatic secretion of the hydrolytic enzymes is hormonally controlled. Cells in the mucosa of the lower duodenum and jejunum produce a small peptide hormone, cholecystokinin (CCK), in response to the presence of lipids and partially digested proteins. CCK acts on the gallbladder stimulating the release of bile. CCK - decreases gastric motility, resulting in a slower release of gastric contents into the small intestine. Secretin- Released in responses to low pH of the chyme entering the intestine. Secretin- causes the pancreas to release a solution rich in bicarbonate that helps neutralize the pH of the intestinal contents,. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Fat emulsification Fatty acids (FAs) can be liberated by simple hydrolysis of the ester bonds in triglycerides, but the insolubility of the triglycerides presents a problem. Emulsification disperses dietary fat into small particles with sufficiently exposed surface area for rapid attack by digestive enzymes. Emulsification accomplished by two complementary mechanisms, Ø detergent properties of the conjugated bile salts Ø mechanical mixing due to peristalsis 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana FAT EMULSIFICATION Digestion occurs following dispersion of dietary fat into small particles with sufficiently exposed surface area for rapid attack by digestive enzymes. This is achieved by detergent action and mechanical mixing, with the detergent effect being supplied by several components, both in the diet and in the digestive juices, but especially by partially digested fats (fatty acid soaps and monacylglycerols) and by bile salts. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Degradation of dietary lipids by pancreatic enzymes The dietary TAG, cholesteryl esters, and phospholipids are enzymically degraded by pancreatic enzymes, whose secretion is hormonally controlled. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana TRIGLYCERIDE\Triacylglycerol DEGRADATION TG – Contains 3 FATTY ACIDS and glycerol backbone broken down to 2 Fatty acids 1 fatty acid attached to a glycerol TG acted on by pancreatic lipase These broken down products are called micelles Micelles- travel through the lumen of the duodenum, walls of the intestines and enter into the enterocytes. As the micelles pushes its way through the intestinal wall, it leaves behind the bile salts. Which is reabsorbed 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Cholesteryl ester degradation Most dietary cholesterol is present in the free (nonesterified) form, with 10%–15% present in the esterified form Cholesteryl esters are hydrolyzed by pancreatic cholesteryl ester hydrolase (cholesterol esterase), which produces cholesterol plus free fatty acids pancreatic cholesteryl ester hydrolase enzyme is greatly increased in the presence of bile salts. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Phospholipid degradation An enzyme, Phospholipase A2 removes one fatty acid from carbon 2 of a phospholipid, leaving a lysophospholipid, which is further acted on by Lysophospholipase to form glycerylphospholipid base. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Absorption of lipids Free fatty acids, free cholesterol, and 2-monoacylglycerol are the primary products of lipid digestion in the jejunum Mixed micelles (bile salts, primary product of digestion) approach the brush border membrane of the enterocytes, site of absorption. Biles salts are reabsorbed into circulation, 5% loss in feaces 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Resynthesis of triacylglycerols and cholesteryl esters mixture of lipids absorbed by the enterocytes migrates to the endoplasmic reticulum of the enterocytes. The endoplasmic reticulum resynthesize the broken down molecules into TG.(fatty acyl-coenzyme A synthetase,(thiokinase) Lysophospholipids are reacylated to form phospholipids by a family of acyltransferases cholesterol is esterified with a fatty acid primarily by acyl CoA:cholesterol acyltransferase long-chain fatty acids entering the enterocytes are used in this fashion to form TAGs, phospholipids, and cholesteryl esters 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Resynthesis of triacylglycerols and cholesteryl esters Short- and medium chain length fatty acids are not reconstituted , but instead they are released into the portal circulation, where they are carried by serum albumin to the liver. Reconstituted TG and cholesterol moves into the Golgi apparatus which packages it to form chylomicrons. Chylomicrons are transported by lipoprotein into the lymphatic systems which travels up to the thoracic duct into the veins. In the blood stream, it binds to it receptors, thus lipoprotein lipase. The lipoprotein lipases break done the TG in the chylomicrons into fatty acids These FA enter the peripheral tissues (skeletal muscles to be used for energy production 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana The FA which moves into adipose tissues are for storage. The chylomicron remnants move to the liver to be processed 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana FAT EMULSIFICATION The bile salts such as cholic acid contain a hydrophobic side and a hydrophilic side, this allowing bile salts to dissolve at an oil-water interface, with the hydrophobic surface in contact with the nonpolar phase and the hydrophilic surface in the aqueous medium. This detergent action emulsifies fats and yields mixed micelles, which allow attack by water-soluble digestive enzymes and facilitate the absorption of lipids through the intestinal mucosa. Mixed Micelles also serve as transport vehicles for those lipids that are less water-soluble than fatty acids, such as cholesterol or the fat- soluble vitamins A, D, E, and K. Thus, efficient absorption of lipids depends on the presence of sufficient bile acids to solubilize the ingested lipids 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Chylomicrons ØLeave the enterocytes and enter the lymphatic capillaries, and eventually pass into the blood stream delivering fats to tissues. ØWalls of blood capillaries have an enzyme called lipoprotein lipase. Lipoprotein lipase ØHydrolysis TG into FA AND GLYCEROL , enabling them to go through the capillary wall where they are oxidized for energy or esterized for storage 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Key concepts: absorption Triglyceride assimilation is key to the survival of the organism. Dietary triglyceride must be hydrolyzed to fatty acids, mono- glycerides and glycerol prior to absorption. Fatty acids must partition to micellar phase for absorption. For transport, triglyceride must be reconstituted from glycerol and fatty acid and incorporated into chylomicrons. 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Lipid malabsorption Lipid malabsorption, resulting in increased lipid loses in the feces, can be caused by disturbances in lipid digestion and/or absorption. Lipid malabsorption can result from several conditions, including CF (causing poor digestion) and short bowel syndrome (causing decreased absorption). 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Lipid malabsorption Lipid malabsorption result in loss of about 30g/day. Which includes fat soluble vitamins and essential Fat in stool Known as steatorrhea Causes Bile salts deficiency in liver disease or due to bile duct obstruction. Pancreatic enzymes deficiency Defective chylomicron synthesis 1/19/24 I BOADU  Kwame Nkrumah University of Science & Technology, Kumasi, Ghana Summary vThere are different kinds of Lipids (Simple lipids, compound lipids, derived lipids, and lipids complexed to other compounds) that play various functions in the body. vThe structure of the Lipid affects its function in the body.. vLipoproteins constitute the body’s “petroleum industry and helps to transport Lipids around the body for cell metabolism 1/19/24 I BOADU