BIOCHEMISTRY-LIPIDS, CHOLESTEROLS, FATTY ACIDS

LIPIDS: TYPES , DIGESTION, METABOLISM , DISORDERS OF LIPID ABSORPTION AND METABOLISM, FUNCTIONS, LDL, HDL & TRIGLICERIDES

1. LIPIDS

2. INTRODUCTION About 99% of the mass of the human body is made up of six elements:  oxygen, carbon, hydrogen, nitrogen, calcium, and phosphorus. Only about 0.85% is composed of another five elements: potassium, sulfur, sodium, chlorine, and magnesium . All 11 are necessary for life.

3. The human body is made up of many chemical elements, including:    Oxygen : The most abundant element in the human body, making up about 61% of its mass.   Carbon:  Makes up about 18% of the human body's mass.   Hydrogen:  Makes up about 10% of the human body's mass.   Nitrogen : Makes up about 3% of the human body's mass.   Calcium : Makes up about 1.4% of the human body's mass .   Phosphorus : Makes up about 1% of the human body's mass.   Potassium:  Makes up about 0.25% of the human body's mass.   Sulfur:  Makes up about 0.25% of the human body's mass.   Sodium : Makes up about 0.15% of the human body's mass.   Trace elements : Make up the remaining less than 10 grams of the human body, and some of them may be essential for life. 

4. Lipids play a very important role in the human body. They not only provide energy but are structural components as well. Lipids may be regarded as organic substances relatively insoluble in water, soluble in organic solution (alcohol , ether , etc.) actually or potentially related to fatty acids and utilized by the living cells . Lipids are substances of biological origin that are soluble in organic solvent such as chloroform but are sparingly soluble in water. Certain vitamins, hormones and most of the non- proteins components of membranes are lipids. Lipids include fats, oil, waxes and related compounds.

5. CLASSIFICATION OF LIPIDS: BLOOR’S CLASSIFICATION

6. FUNCTIONS OF LIPIDS Storage form of energy (triglycerides) Structural components of biomembrane. Metabolic regulators (steroid hormones) Act as surfactants, detergents and emulsifying agents (amphipathic lipids) Act as electric insulators in neurons Provide insulation against changes in external temperature (subcutaneous fat) Give shape and contour to the body.

7. Saturated fatty acids are saturated with hydrogen since single bonds increase the number of hydrogens on each carbon. Stearic acid and palmitic acid, which are commonly found in meat, are examples of saturated fats. When the hydrocarbon chain contains a double bond, the fatty acid is said to be unsaturated.

8. FATTY ACIDS Fatty acids are monocarboxylic acids with chainlength 2–36 carbon atoms and 0- 6 double bonds. Their physicochemical properties are reflected also in the compounds, where fatty acids represent an important component (phospholipids, triglycerides), as well as in higher organized structures (plasma membranes, lipoproteins).

9. MONOUNSATURATED FATTY ACIDS (MUFA) AND POLYUNSATURATED FATTY ACIDS (PUFA) – CLINICAL SIGNIFICANCE   Lower cholesterol: MUFAs and PUFAs can help lower bad cholesterol (LDL) and increase good cholesterol (HDL).    Improve heart health: MUFAs and PUFAs can help stabilize heart rhythms and reduce the risk of coronary heart disease.    Improve insulin sensitivity: MUFAs and PUFAs can help the body manage blood sugar and metabolism, which may reduce the risk of diabetes.   

10. Reduce inflammation: MUFAs and PUFAs can help reduce inflammation.  Support cell and nerve maintenance: MUFAs and PUFAs can help maintain cells and nerves.  Aid in digestion: MUFAs and PUFAs can aid in digestion.  Promote mood: Omega-3 fatty acids, which are rich in PUFAs, can help promote mood and alleviate depression and anxiety.  Support fetal development: Omega-3 fatty acids, which are rich in PUFAs, can promote normal fetal development

11. In   TRANS FATTY ACIDS , the two hydrogen atoms near the double bonds are on the opposite sides of the molecule–what makes them straight and thus more rigid and solid–, while in the regular  cis  fatty acids they are on the same side, what makes them more flexible and thus liquid.

12. TRANS FATTY ACIDS (TFA) Trans fatty acids (with double bonds having trans configuration) are formed during the partial hydrogenation of vegetable oils. TFA are more atherogenic than saturated fatty acids. It increases catabolism of apo A- I, decreases high- density lipoprotein (HDL) and increases low-density lipoprotein (LDL) levels. They are widely used in food industry because of their long shelf-life. They are present in fast food preparation, processed foods, bakery products, dairy products and in partially hydrogenated vegetable oils. They are generally considered to be injurious to health. Oils containing PUFA also have high content of TFA. Fast food preparations have a high TFA content.

13. ESSENTIAL FATTY ACID They cannot be synthesised in the body and must be provided in the diet . Lack of EFA in the diet can produce growth retardation and other deficiency manifestation symptoms. Chemically, they are polyunsaturated fatty acids , namely linoleic acids . Functions of EFA It is required for the membrane structure and function. Helps in transport of cholesterol. Helps in formation of lipoproteins. Prevention of fatty liver etc. It is also required for the synthesis of another group of compounds, namely eicosanoids. Fats with high content of polyunsaturated fatty acids tends to lower serum level of cholesterol.

14. DIGESTION AND ABSORPTION OF LIPIDS Dietary fats include oil, ghee, butter, animal and vegetable oils. They are digested in various stages as they pass through the alimentary canal. Lipids such as triglycerides and phospholipids are converted into glycerol and fatty acid with the help of lingual lipase and esterase in gastrointestinal tract. Digestion in Mouth Little digestion occurs in the mouth ; lingual lipase is secreted by sublingual gland in the mouth. The process of chewing and secretion of lingual lipase help in breakdown of triglycerides. Digestion in Stomach Gastric lipase secreted by the chief cells in the fundus of stomach has limited action in digestion. The secretion of gastric lipase is stimulated by the gastric lipase help in hydrolysis of triacylglycerol (mostly unsaturated) into free fatty acid and glycerol.

15. Digestion in Small Intestine Emulsification is a primary step for digestion of lipids. The lipids are dispersed into small droplets. Surface tension here play important role. Due to decrease in surface tension, it helps in emulsification of fat and on other hand, it helps in digestion and this process is favoured by: Bile salts (detergent action) Peristalsis (mechanical mixing). Lipolytic Enzymes in Intestines Pancreatic lipase with colipase Cholesterol esterase Phospholipase A2.

16. LACTEALS are present in the small intestine. The mucosa of the small intestine consists of a large number of finger-like projections called villi . Each villus is lined by columnar epithelium. Underneath the epithelial layer, a lymphatic vessel called lacteal is present that opens up to the lymphatic system. They help in the absorption of fatty acids .

17. Bile salts cluster around the products of fat digestion to form structures called  micelles , which help the fats get close enough to the microvilli of intestinal cells so that they can be absorbed .

18. DISORDERS RELATED TO DIGESTION & ABSORPTION OF LIPIDS Defective Digestion In steatorrhea, daily excretion of fat in feces is more than 6 g/day. (Greek word, ‘steat’, means fat). It is due to chronic diseases of pancreas. In such cases, unsplit fat is seen in feces. Defective Absorption Defective absorption may be due to diseases: Celiac disease - sprue , Crohn’s disease .

19. Chyluria – Presence of chyle in urine There is an abnormal connection between the urinary tract and lymphatic drainage system of the intestine. Celiac disease- Sprue is an autoimmune condition that damages the lining of the small intestine. This damage comes from a reaction to eating gluten. This is a substance that is found in wheat , barley, and possibly oats. It is also found in food made from these ingredients. The damaged intestine is not able to fully absorb nutrients from food . Crohn's disease is a type of inflammatory bowel disease (IBD). It causes swelling of the tissues (inflammation) in your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition.

20. Cholesterol is a precursor molecule for many compounds, including:  Steroid hormones : Cholesterol is the precursor for all classes of steroid hormones, including glucocorticoids , mineralocorticoids , and sex hormones. These hormones are synthesized in the placenta, ovaries, testes, and adrenal cortex.  Vitamin D : Cholesterol is a precursor for vitamin D, which is important for calcium metabolism.  Bile acids : Cholesterol can be converted into bile acids, which are excreted in bile.   COMPOUNDS FORMED FROM CHOLESTEROL

21. PLASMA LIPIDS/LIPOPROTEINS Plasma lipids comprises of cholesterol, triglycerides (TG), phospholipids. They are insoluble in water so they need the help of some transporter/carrier in plasma. So, they are complexed with protein to form lipoproteins. Structure of Lipoproteins A lipoproteins consists of neutral lipids core (with triacylglycerol) and cholesterol ester surrounded by coat shell of phospholipids, apoprotein and cholesterol.

22. CLASSIFICATION OF LIPOPROTEINS Major types of lipoproteins are as follows: Chylomicrons: Contain apoprotein B- 48. Very low- density lipoproteins (VLDL): Main apoproteinis B-100. Intermediate density lipoproteins (IDL) Low- density lipoproteins (LDL): Major apoprotein in LDL is B- 100. High- density lipoproteins (HDL): Major apoprotein in HDL is apo A.

23. LIPID PROFILE A lipid panel (Profile)measures five different types of lipids from a blood sample, including: Total cholesterol : This is your overall cholesterol level — the combination of LDL-C, VLDL-C and HDL-C. Low-density lipoprotein (LDL) cholesterol : This is the type of cholesterol that’s known as “bad cholesterol.” It can collect in your blood vessels and increase your risk of cardiovascular disease. Very low-density lipoprotein (VLDL) cholesterol :  This is a type of cholesterol that’s usually present in very low amounts when the blood sample is a fasting samples since it’s mostly comes from food you’ve recently eaten. An increase in this type of cholesterol in a fasting sample may be a sign of abnormal lipid metabolism .

24. High-density lipoprotein (HDL) cholesterol : This is the type of cholesterol that’s known as “ good cholesterol .” It helps decrease the buildup of LDL in your blood vessels. Triglycerides : This is a type of fat from the food we eat. Excess amounts of triglycerides in your blood are associated with cardiovascular disease and pancreatic inflammation. NORMAL VALUES Total cholesterol : Below 200 mg/ dL . High-density lipoprotein (HDL) cholesterol : Above 60 mg/ dL . Low-density lipoprotein (LDL) cholesterol : Below 100 mg/ dL (For people who have diabetes: Below 70 mg/ dL ). Triglycerides : Below 150 mg/ dL .

25. ATHEROSCLEROSIS It is the buildup of fats, cholesterol and other substances in and on the artery walls. This buildup is called plaque. The plaque can cause arteries to narrow, blocking blood flow. The plaque can also burst, leading to a blood clot. Although atherosclerosis is often considered a heart problem, it can affect arteries anywhere in the body. Atherosclerosis can be treated. Healthy lifestyle habits can help prevent atherosclerosis . Atherosclerosis, also known as arteriosclerosis , is a chronic disease that causes plaque to build up in the walls of your arteries, which can lead to a number of serious complications: 

26. Atherosclerosis is caused by a buildup of plaque , which is made up of cholesterol, calcium, fatty substances, cellular waste, and fibrin. This buildup can partially or completely block blood flow to the heart.    Risk of heart attack and stroke Atherosclerosis can increase the risk of heart attack and stroke.    Aneurysms Atherosclerosis can cause aneurysms, which can be life-threatening if they burst.  Chronic kidney disease .  Atherosclerosis can cause the arteries leading to the kidneys to narrow. Narrowing of these arteries prevents enough oxygen-rich blood from reaching the kidneys. The kidneys need enough blood flow to help filter waste products and remove excess fluids.

27. An aneurysm is a bulging, weakened area in the wall of a blood vessel resulting in an abnormal widening or ballooning greater than 50% of the vessel's normal diameter (width)