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Questions and Answers
Which enzyme initiates the hydrolysis of triacylglycerol in the stomach?
Which enzyme initiates the hydrolysis of triacylglycerol in the stomach?
What is formed as a result of pancreatic lipase activity on triacylglycerol?
What is formed as a result of pancreatic lipase activity on triacylglycerol?
Which lipid can be absorbed without digestion?
Which lipid can be absorbed without digestion?
How are short chain fatty acids and glycerol absorbed into circulation?
How are short chain fatty acids and glycerol absorbed into circulation?
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Which enzyme acts on 1-monoacylglycerol during lipid digestion?
Which enzyme acts on 1-monoacylglycerol during lipid digestion?
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What is a key function of cholesterol esterase in lipid digestion?
What is a key function of cholesterol esterase in lipid digestion?
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Which lipids are primarily digested by pancreatic lipase?
Which lipids are primarily digested by pancreatic lipase?
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Which of the following vitamins is considered fat-soluble?
Which of the following vitamins is considered fat-soluble?
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What role does the microsomal system play in fatty acid metabolism?
What role does the microsomal system play in fatty acid metabolism?
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Which fatty acids must be included in the diet of mammals due to their inability to synthesize them?
Which fatty acids must be included in the diet of mammals due to their inability to synthesize them?
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What is the principal method of oxidation for fatty acids?
What is the principal method of oxidation for fatty acids?
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Where does the activation of fatty acids into acyl CoA occur?
Where does the activation of fatty acids into acyl CoA occur?
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Why can't the brain utilize fatty acids as a source of energy?
Why can't the brain utilize fatty acids as a source of energy?
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What regulates the entry of fatty acids into the mitochondria for β-oxidation?
What regulates the entry of fatty acids into the mitochondria for β-oxidation?
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What are the three substances that make up ketone bodies synthesized during excessive fatty acid oxidation?
What are the three substances that make up ketone bodies synthesized during excessive fatty acid oxidation?
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Which of the following increases the free fatty acid (FFA) levels in the body?
Which of the following increases the free fatty acid (FFA) levels in the body?
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What is the primary source of acetyl CoA derived from carbohydrates?
What is the primary source of acetyl CoA derived from carbohydrates?
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Which option correctly describes the fate of acetyl CoA?
Which option correctly describes the fate of acetyl CoA?
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How does nutritional state influence lipogenesis?
How does nutritional state influence lipogenesis?
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What type of modification inactivates acetyl-CoA carboxylase?
What type of modification inactivates acetyl-CoA carboxylase?
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Which hormone activates acetyl-CoA carboxylase by dephosphorylation?
Which hormone activates acetyl-CoA carboxylase by dephosphorylation?
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What is the result of high levels of long chain fatty acyl-CoA in the cell?
What is the result of high levels of long chain fatty acyl-CoA in the cell?
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In which state do the enzymes responsible for fatty acid synthesis increase in total amount?
In which state do the enzymes responsible for fatty acid synthesis increase in total amount?
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What role does glucagon play in the regulation of fatty acid synthesis?
What role does glucagon play in the regulation of fatty acid synthesis?
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What is the primary effect of ketosis on the body's metabolism?
What is the primary effect of ketosis on the body's metabolism?
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What is produced during the hydrolysis of triacylglycerol in adipose tissue?
What is produced during the hydrolysis of triacylglycerol in adipose tissue?
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Which hormone activates hormone-sensitive lipase in adipose tissue?
Which hormone activates hormone-sensitive lipase in adipose tissue?
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What key regulatory enzyme is involved in cholesterol synthesis?
What key regulatory enzyme is involved in cholesterol synthesis?
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Which factor contributes to the onset of ketosis?
Which factor contributes to the onset of ketosis?
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How does the presence of sufficient cholesterol affect HMG-CoA reductase?
How does the presence of sufficient cholesterol affect HMG-CoA reductase?
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What is a common symptom of ketosis that can be detected by breath odor?
What is a common symptom of ketosis that can be detected by breath odor?
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In which cellular compartments does cholesterol synthesis primarily occur?
In which cellular compartments does cholesterol synthesis primarily occur?
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What is the primary function of apo C-II in lipid metabolism?
What is the primary function of apo C-II in lipid metabolism?
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What is the composition of VLDL particles secreted by the liver?
What is the composition of VLDL particles secreted by the liver?
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What happens to chylomicrons as they lose triglycerides?
What happens to chylomicrons as they lose triglycerides?
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What is the main role of LDL in the body?
What is the main role of LDL in the body?
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How do LDL particles primarily interact with cells?
How do LDL particles primarily interact with cells?
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What can occur when cholesterol infiltrates arterial walls?
What can occur when cholesterol infiltrates arterial walls?
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Which lipoprotein remnant is formed after VLDL loses triglycerides?
Which lipoprotein remnant is formed after VLDL loses triglycerides?
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What correlation has been observed with high LDL concentrations in the blood?
What correlation has been observed with high LDL concentrations in the blood?
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What is the primary function of statin drugs in relation to cholesterol?
What is the primary function of statin drugs in relation to cholesterol?
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How is cholesterol transported in the plasma?
How is cholesterol transported in the plasma?
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What constitutes the lipid core of a typical lipoprotein?
What constitutes the lipid core of a typical lipoprotein?
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What is the primary role of apolipoproteins in lipoproteins?
What is the primary role of apolipoproteins in lipoproteins?
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What is the primary method by which cholesterol is eliminated from the body?
What is the primary method by which cholesterol is eliminated from the body?
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Which lipoprotein class is primarily responsible for transporting dietary lipids from the intestine?
Which lipoprotein class is primarily responsible for transporting dietary lipids from the intestine?
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What is the role of apo C-II in relation to lipoprotein lipase?
What is the role of apo C-II in relation to lipoprotein lipase?
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Which of the following lipoproteins has the highest percentage of protein?
Which of the following lipoproteins has the highest percentage of protein?
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Study Notes
Lipid Metabolism
- Learning Outcomes: Students should be able to identify lipid digestion, absorption, secretion, synthesis, and oxidation pathways, along with cholesterol and ketone body metabolism, and lipoprotein structures and metabolism. They should also be able to interpret symptoms, signs, and lab findings of inborn metabolic disorders. Students should also identify the etiology of metabolic disturbances using case study reports.
Digestion of Lipids
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Major Lipids: The primary dietary lipids are triacylglycerols, phospholipids (to a lesser extent), fat-soluble vitamins (A, D, E, and K), and other lipids (cholesterol, cholesterol esters, and free fatty acids).
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Lingual and Gastric Lipases: Initiate triacylglycerol (TAG) hydrolysis in the mouth and stomach by attacking the sn-3 ester bond, forming 1,2-diacylglycerols and free fatty acids.
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Pancreatic Lipase: Secreted into the small intestine; needs colipase for activity. Specifically targets positions 1 and 3 of the TAG molecule, producing 2-monoacylglycerols and free fatty acids.
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Intestinal Lipase: Acts on 1-monoacylglycerols, converting them into glycerol and fatty acids (FAs).
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Cholesterol Esters Digestion: Cholesterol esterase enzyme breaks down cholesterol esters into cholesterol and fatty acids.
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Phospholipids (PLs): May be absorbed without digestion. Pancreatic phospholipase A2, in the presence of calcium ions (Ca2+), produces lysophospholipids and FAs.
Absorption of Lipids
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Short-Chain FAs and Glycerol: Water-soluble; absorbed into the portal circulation to the liver.
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Other Lipids: Water-insoluble; combine with bile salts to form micelles (water-soluble complexes), which enter mucosal cells.
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Reacylation: Within intestinal cells, micellar lipids are reconstituted into triacylglycerols (TAGs).
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Chylomicron Formation: TAGs, phospholipids, and cholesterol combine with apolipoprotein B-48 to form chylomicrons (lipoproteins). These are then secreted into lymphatics, then into the thoracic duct, and finally into the bloodstream.
Lipid Malabsorption (Steatorrhea)
- Causes: Bile salt deficiency (e.g., bile duct obstruction), pancreatic lipase deficiency (e.g., pancreatic duct obstruction, cystic fibrosis), and short bowel syndrome.
Fatty Acid Synthesis (Lipogenesis)
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Basic Strategy: Synthesis of palmitate (16C) from acetyl-CoA (2C), followed by chain elongation of palmitate (to create long-chain fatty acids) and desaturation.
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Systems Involved: Lipogenesis occurs through cytoplasmic (extramitochondrial) and microsomal systems. The cytoplasmic system is for "de novo" synthesis.
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Intracellular Site: Cytoplasm
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Active Tissues: Lipogenesis is active in the liver, lactating mammary glands, adipose tissue, and to a lesser extent in the kidney, brain, and lungs.
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Starting and End Products: Acetyl CoA is converted to palmitate.
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Requirements: Enzymes (acetyl-CoA carboxylase and fatty acid synthase complex), coenzymes (NADPH, Mn2+, biotin, and pantothenic acid), CO2, and ATP.
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Rate-Limiting Enzyme: Acetyl CoA carboxylase catalyzes the carboxylation of acetyl-CoA to malonyl-CoA.
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Fatty Acid Synthase Complex: A multienzyme complex; a dimer with 7 enzyme activities and an acyl carrier protein (ACP).
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Odd-Numbered Fatty Acids: If propionyl CoA is used as a primer, odd-numbered carbon fatty acids result.
Sources of NADPH and Acetyl CoA
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NADPH Source: Pentose phosphate pathway.
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Acetyl CoA Sources:
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Carbohydrates: oxidative decarboxylation of pyruvate in the mitochondria
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Fats: Oxidation of fatty acids is the richest source; for example, palmitate gives eight active acetates, while glucose gives two.
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Proteins: Ketogenic amino acids form active acetate or acetoacetate. Glucogenic amino acids form pyruvate, which then forms active acetate.
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Acetyl CoA and Lipogenesis: Acetyl CoA cannot enter the cytosol directly; it is converted to citrate which then is transported into the cytosol to form acetyl CoA and oxaloacetate through ATP-citrate lyase.
Regulation of Lipogenesis
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Nutritional State: High carbohydrate diet promotes lipogenesis; restricted caloric intake, high-fat diets, and diabetes mellitus depress lipogenesis.
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Short-Term Control: Allosteric regulation (e.g., citrate activates acetyl-CoA carboxylase; long-chain fatty acyl-CoAs inhibit it) and covalent modification (e.g., phosphorylation inactivates acetyl-CoA carboxylase; insulin dephosphorylates and activates it).
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Long-Term Control: Changes in gene expression—regulating enzyme synthesis rates— adapt to the body's physiologic needs. Insulin promotes enzyme biosynthesis; glucagon has the opposite effect.
Fatty Acid Oxidation
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Energy Source: Oxidation of fatty acids is the primary energy source during starvation or when glucose supplies are low. 1 gram of fat gives approximately 9 kilocalories.
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Sources of Fatty Acids (FAs): Diet and lipolysis from adipose tissue.
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Oxidation Methods: β-oxidation (the principal method), α-oxidation, ω-oxidation, and peroxisomal fatty acid oxidation.
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β-oxidation Site: Mitochondria (primarily in the liver, kidneys, and heart). The brain cannot efficiently use fatty acids as an energy source, due to diminished beta-oxidation enzymes.
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β-oxidation Steps: (1)Activation, (2)Transport, and (3)Oxidation.
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Requirements: (1) Activation: Fatty acid + ATP + CoA → Acyl-CoA + PP; + AMP; then transport into the mitochondria, (2) Transport: acyl CoA by carnitine shuttle; (3) Oxidation: repeated cycles using acyl-CoA dehydrogenase, hydration, dehydrogenase, and thiolysis yielding acetyl CoA, NADH, FADH2, and shortening of the fatty acyl chain one carbon at a time.
Regulation of Fatty Acid Oxidation
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Availability of Free Fatty Acids (FFAs): The availability of FFAs regulates the net utilization through beta-oxidation. Glucagon increases FFA levels; insulin has the opposite effect.
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Rate-Limiting Enzyme: Carnitinepalmitoyl transferase-I (CPT-I), the regulator of fatty acid entry to the mitochondria, is inhibited by malonyl-CoA. High rates of de novo fatty acid synthesis lead to inhibition of β-oxidation.
Metabolism of Ketone Bodies
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Ketogenesis: During high rates of fatty acid oxidation, excess acetyl-CoA is converted into ketone bodies that include acetoacetic acid, β-hydroxybutyric acid, and acetone.
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Liver Exclusivity: Synthesized exclusively in the liver mitochondria.
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Fuel Source: Ketone bodies are important fuel sources for extrahepatic tissues (tissues outside of the liver).
Ketosis
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Definition: Ketosis is the presence of an increased amount of ketone bodies in the blood (ketonemia) and in the urine (ketonuria).
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Causes: Uncontrolled diabetes mellitus, starvation, high-fat diets.
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Consequences: Metabolic acidosis, compensatory hyperventilation, acetone breath, osmotic diuresis, loss of cations (sodium and potassium), dehydration, and coma.
Metabolism of Adipose Tissue
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Primary Role: Storage of triacylglycerols (TAGs).
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Continuous Cycle: TAGs in adipose tissue continually undergo cycles of lipolysis (hydrolysis) and re-esterification.
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TAG Synthesis: Synthesized from acyl CoA and glycerol 3- phosphate; the glycerol 3-phosphate is supplied from glucose metabolism through glycolysis, as glycerol kinase is absent in adipose tissue.
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Hormone-Sensitive Lipase: Hydrolyzes TAGs into free fatty acids and glycerol. Insulin inhibits this enzyme; glucagon, epinephrine, and norepinephrine activate it.
Cholesterol Metabolism
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Function: Necessary for cell membrane structure, bile acid and bile salt synthesis, steroid hormone synthesis (in particular, androgens in males and estrogens in women), and vitamin D3 synthesis.
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Clinical Significance: Abnormal cholesterol deposition in coronary arteries leads to atherosclerosis and risks for cardiovascular diseases.
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Structure: Cholesterol is a steroid compound with a hydrocarbon tail for solubility. It has a steroid nucleus and four hydrocarbon rings.
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Cholesterol Synthesis in the body: The major sites for cholesterol synthesis are the liver, adrenal cortex, testes, ovaries, and intestines. All nucleated cells can synthesize cholesterol. Cholesterol synthesis occurs in the cytoplasm and endoplasmic reticulum from acetyl-CoA. HMG-CoA reductase is a key regulatory enzyme.
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Regulation of Cholesterol Synthesis: (1) Long-term regulation: When sufficient cholesterol is present, transcription of the HMG-CoA reductase gene is suppressed. (2) Short-term regulation: (Activated by dephosphorylation); feedback inhibition by cholesterol; hormonal control (insulin and thyroid hormone increase; glucagon and glucocorticoids decrease). Statins function as competitive inhibitors of HMG-CoA reductase.
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Cholesterol Transport: Transported in plasma predominantly as cholesterol esters associated with lipoproteins.
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Cholesterol Degradation: Eliminated from the body by conversion to bile acids and bile salts, which are excreted in the feces (about 1 gram/day).
Lipid Transport
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Plasma Lipids: Lipids are insoluble in water and require carriers for transport in the plasma, forming lipoproteins. Non-esterified fatty acids (NEFAs) complex with albumin.
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Lipoprotein Classifications: Lipoproteins are categorized by density differences, including chylomicrons, very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and lipoprotein (a) (Lp(a)).
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Structure of a typical lipoprotein: A typical lipoprotein has a core of nonpolar triacylglycerol and cholesteryl ester, surrounded by a monolayer of phospholipids and cholesterol with integral proteins (apolipoproteins). Some apolipoproteins are integral (cannot be removed) and others can transfer to other lipoproteins.
Functions of Apolipoproteins
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General Apolipoprotein Function: Promote lipid solubility and stability in the plasma.
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Specific Apolipoprotein Functions: Act as enzyme activators (e.g., apo C-II for lipoprotein lipase) and inhibitors (e.g., apo C-III for lipoprotein lipase), and ligands to specific lipoprotein receptors (e.g., apo B-100 and apoE for LDL receptors).
Metabolism of Plasma Lipoproteins
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Chylomicrons: Synthesized in intestinal cells, transport dietary lipids from the gut to peripheral tissues, and the liver. Contain lipids (mainly TAGs), apo B-48, apo C-II, and apo E as the protein component. Apo C-ll activates lipase; the reduced TAG content then results in chylomicrons breaking down to remnants absorbed by the liver.
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Very-Low-Density Lipoproteins (VLDL): Synthesized in the liver, transport endogenously synthesized lipids (mainly TAGs) to peripherals tissues. Contain lipids (mainly TAGs), apo B-100, apo C-II, and apo E as the protein component. As TAG is hydrolyzed by lipoprotein lipase, the remaining particles are called VLDL remnants (or IDL). VLDL remnants bind via apo E to hepatic receptors; triglycerides are used in peripheral uptake, and apo C-II may transfer, with subsequent metabolism by the liver.
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Low-Density Lipoproteins (LDL): LDL transports cholesterol from the liver to peripheral tissues. Derived from VLDL remnants. Contain lipids (cholesterol, cholesterol esters, and phospholipids), and apo B-100 as the protein component. LDL receptors are bound to apo B-100, and LDL binds; the receptor-LDL receptor complex is internalized by endocytosis.
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High-Density Lipoproteins (HDL): Synthesized in the liver and intestines. Acts as a "reservoir" for apo C-II; transfers apo C-II to chylomicrons and VLDL. Removes free cholesterol from peripheral tissues back to the liver (reverse cholesterol transport). HDL cycle involves cholesterol transfer and conversion from HDL3 to HDL2 (spherical shape) via lecithin-cholesterol acyltransferase (LCAT). HDL and cholesterol esters are then removed through liver receptors (apo A-1 binding).
HDL and its Significance
- HDL inverse correlation with myocardia infarction: HDL levels are inversely correlated with myocardial infarction. HDL is therefore considered a "good cholesterol," which can prevent cardiovascular diseases.
LDL and its Clinical Significance
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Foam Cells: Cholesterol infiltrates arterial walls and is taken up by macrophages, forming foam cells and subendothelial space. This can lead to atherosclerosis, myocardial infarction (MI), and an increased risk of coronary artery disease.
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Familial Hypercholesterolemia: Defect or mutation in apo B-100 binding regions in the LDL receptors causes increased LDL levels and hypercholesterolemia and therefore possible atherosclerosis and coronary artery disease.
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LDL and Coronary Heart Disease: LDL level has been positively correlated to the risk of coronary heart disease.
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Description
Test your knowledge on the processes of lipid digestion and metabolism. This quiz covers key enzymes, absorption methods, and the roles of various lipids in the body. Challenge yourself and learn more about the science behind lipids!
