Lipid Metabolism and Lipoproteins Quiz

Lipid Metabolism

• Lipids are a major source of energy for the body
• About 100-150 grams of lipids are consumed daily by adults.
• Triacylglycerols (TGs) are the primary dietary lipids, constituting most fat and oils.
• Phospholipids and cholesterol are also present in the diet.
• Pancreatic lipase is crucial for TG digestion, activated by bile salts and calcium ions.
• Ingested TGs are emulsified in the stomach by gastric contractions and in the intestines by bile salts.
• Lipases then hydrolyze TGs into smaller components in the small intestine.
• End products of TG digestion are 2 monoacylglycerols, 1 monoacylglycerols, glycerol and saturated/unsaturated fatty acids.
• Short-chain fatty acids (<12 carbons) and glycerol are water-soluble and absorbed directly into the portal system, leading to the liver.
• Other lipids (long-chain fatty acids) combine with bile salts to form micelles, enhancing absorption into mucosal cells in the intestines.
• Absorbed long-chain fatty acids are re-esterified into TGs within the intestinal cells.
• These TGs, along with cholesterol and phospholipids, are assembled into chylomicrons.
• Chylomicrons enter the lymphatic system, eventually entering the bloodstream at the thoracic duct.
• Lipoprotein lipase (LPL) hydrolyzes chylomicron TGs into free fatty acids and glycerol, enabling absorption by tissue cells.
• These fatty acids are then metabolized for energy or stored as TGs within the tissue cells.
• The body uses different types of lipoproteins to transport lipids within the bloodstream (chylomicrons, VLDL, IDL, LDL, and HDL). These lipoproteins differ in lipid and protein composition, size, and density, all crucial for lipid transportation.

Digestion and Absorption

• Digestion of lipids starts in the small intestine.
• The emulsified TGs are hydrolyzed by pancreatic lipase.
• The result of the hydrolysis can be 2-monoacylglycerol or 1-monoacylglycerol, which can be further hydrolyzed to free glycerol.
• The end products are 2 monoacylglycerols, 1 monoacylglycerols, glycerol and saturated/unsaturated fatty acids.

Plasma Lipids

• Lipids within the bloodstream are transported by lipoproteins.
• These lipoproteins have different functions based on their composition and sizes (e.g., Chylomicrons, VLDL, IDL, LDL, HDL).
• Apolipoproteins (Apo) are proteins associated with lipoproteins.
• Apolipoproteins serve as receptors for cells and as activators/co-enzymes for enzymes involved in lipoprotein metabolism.
• Five major classes of apolipoproteins (A-E) with subclasses are important in lipid metabolism.

Oxidation of Fatty Acids

• Fatty acids are taken by cells and used for energy production.
• In prolonged fasting, tissues utilize fatty acids and/or ketone bodies.
• β–oxidation is the primary pathway for fatty acid breakdown.
• The β-carbon is oxidized in this process. This happens within the mitochondria.
• Fatty acids are not directly absorbed by mitochondria, forming acyl-carnitine to travel through the membranes.

Site

• Mitochondria are the primary site of fatty acid oxidation.
• The inner mitochondrial membrane is impermeable to fatty acids; therefore, fatty acids react with carnitine to generate acyl-carnitine which can enter the mitochondria.

Importance of β-oxidation

• Provides a source of energy.
• Generates acetyl CoA for energy production and other processes.
• The process of ketone body formation in the liver.

Oxidation of fatty acids with odd number of carbon atoms

• Fatty acid oxidation with odd number of carbon atoms proceeds similarly to even-numbered fatty acids.
• However, propionyl CoA is the final product.
• Propionyl CoA is converted to succinyl CoA for entry into the citric acid cycle.

a-oxidation

• A minor pathway for fatty acid oxidation
• Oxidation of the carbon atom adjacent to the carboxyl group by removing a carbon.
• Happens primarily in brain tissue.

w-oxidation

• A minor pathway for fatty acid oxidation involving hydroxylation in the endoplasmic reticulum.
• Hydroxylation typically occurs on the methyl carbon.
• The hydroxylated fatty acid can be further oxidized to a dicarboxylic acid.
• Occurs with medium-chain fatty acids.

Biosynthesis of fatty acids (Lipogenesis)

• Occurs in the liver and adipose tissue cytosol.
• Acetyl CoA is a crucial precursor for fatty acids.
• The process utilizes NADPH as a source of reducing equivalents.
• Requires ATP for many enzymatic processes.
• It is an energetically expensive process.
• Lipogenesis mainly occurs during and after consumption of a carbohydrate- rich meal.

Palmitate Formation

• Palmitic acid (16-carbon saturated fatty acid) is the primary product.
• Palmitic acid is released from the fatty acid synthase complex.
• The cycle continues after each repetition.

Fate of palmitate

• Palmitate can be used in different processes, including esterification with glycerol or cholesterol.
• Elongation can increase the number of carbon atoms in palmitate.
• Desaturation introduces double bonds to produce other fatty acids.

Regulation of fatty acid biosynthesis

• Insulin stimulates fatty acid synthesis by influencing acetyl-CoA carboxylase.
• Citrate activates acetyl-CoA carboxylase, also known as the rate-limiting step in fatty acid synthesis.
• Long-chain acyl CoAs inhibit acetyl-CoA carboxylase, thus reducing synthesis.

Triacylglycerol Metabolism

• TGs are synthesized in adipose tissue as the major energy storage.
• Fatty acids must first be activated to acyl-CoA.
• Glycerol phosphate is synthesized from glucose or glycerol by two primary methods.
• These two forms of glycerol phosphate are important in the synthesis of triacylglycerol.

Lipolysis (TG Degradation)

• This process breaks down stored TGs into glycerol and fatty acids in adipose tissue.
• Increased energy demand (i.e., starvation, uncontrolled diabetes, low carbohydrate diet) leads to higher lipolysis.
• Hormone-sensitive lipase (HSL) enzyme plays a crucial role in lipolysis.

Lipolysis Regulations

• Several hormones (epinephrine, nor epinephrine, growth hormone, TSH, and caffeine) stimulate lipolysis.
• Insulin can inhibit lipolysis through the inhibition of cAMP-dependent protein kinase.
• Long-chain acyl-CoA inhibits acetyl-CoA carboxylase, lowering rates of fatty acid synthesis.
• Nicotinic acid and prostaglandin E reduce lipolysis through their effects on adenylate cyclase.

Ketone Bodies Metabolism

• Ketone bodies are produced by the liver primarily during periods of starvation or carbohydrate restriction or with diabetes.
• The liver creates ketone bodies from acetyl CoA.
• During starvation or diabetes, the body utilizes ketone bodies from the liver as an energy source.
• Ketone bodies include acetoacetic acid, β-hydroxybutyric acid, and acetone.
• These compounds provide energy for vital organs like the heart and skeletal muscle.
• The synthesis primarily happens in the liver from molecules like acetyl CoA.

Ketosis

• Ketosis is a metabolic condition characterized by elevated levels of blood and urine ketone bodies.
• Conditions such as starvation, carbohydrate-poor diets, and uncontrolled diabetes can induce ketosis.

Ketone Bodies Oxidation (Ketolysis)

• Extrahepatic tissues primarily utilize ketone bodies for energy.
• Liver lacks the key enzymes for ketone body breakdown.
• Oxidation of ketone bodies follows specific pathways.
• Results in the generation of ATP.

Metabolism of Cholesterol

• Cholesterol is synthesized within the body.

• The main site of cholesterol production is the liver.

• Other tissues such as adrenal cortex, skin, testis, and intestine also synthesize cholesterol.

• Cholesterol synthesis occurs within the cytoplasm of cells.

• The process begins from acetoacetyl coA and mevalonate from active acetyl CoA.

• The key enzyme in cholesterol synthesis is HMG-CoA reductase.

• Cholesterol intake decreases HMG-CoA reductase activity.

• Fasting reduces cholesterol production by limiting the availability of acetyl CoA and NADPH.

• Cholesterol can undergo reversible phosphorylation-dephosphorylation.

• The phosphorylated form is less active.

• Cholesterol is crucial for many bodily functions, including the structure of cells and hormones.

• Excess cholesterol can lead to health problems.

• Cholesterol can be excreted from the body via bile acids and bile salts in the feces.

• Some cholesterol undergoes modification by bacteria into coprostanol and cholestanol.

• Plasma cholesterol exists as free cholesterol and cholesteryl esters.

Test your knowledge on lipid metabolism and the role of lipoproteins such as chylomicrons, VLDL, LDL, and HDL. This quiz covers essential functions, enzyme interactions, and metabolic processes related to fatty acids. Join now to deepen your understanding of lipid biochemistry!