Lipoproteins and Chylomicrons Quiz

Lipid Metabolism

• Lipids are transported in plasma primarily as lipoproteins
• Lipoproteins are composed of proteins and lipids
• Four major lipid classes in lipoproteins: triglycerides (TAG), cholesterol ester (CE), cholesterol (C), and phospholipids (PL)
• Four major lipoprotein groups (CM, VLDL, LDL, and HDL)
• Apolipoproteins (apo) are proteins that make up lipoproteins, enabling them to be transported and utilized by tissues
• Major apolipoproteins include: Apo A-I, A-II, B-48, B-100, C-II, E
• Lipoprotein structure: inner core of nonpolar lipids (TAG, CE); surface layer of amphipathic lipids (PL, C, apolipoproteins)
• Fatty acids are also transported bound to albumin
• Lipid digestion and absorption occur in stomach and small intestine
• Dietary lipids are emulsified by bile salts, and digested by pancreatic enzymes
• Lipid products are absorbed by enterocytes, resynthesized into TAG and CE, and packaged into chylomicrons
• Chylomicrons are secreted into lacteals, travel through thoracic duct, and enter circulation
• Utilization of chylomicrons: HDL and lipoprotein lipase degrade TAG
• Steatorrhea (excess fat in feces) can be caused by impaired digestion/absorption
• Lipogenesis (triacylglycerol synthesis) in liver from glucose occurs in the cytosol

Learning Objectives: Lipid Metabolism cont.

• Lipogenesis pathway details: citrate synthase, malic enzyme, and acetyl-CoA carboxylase roles, and fatty acid synthase, acetyl-CoA, ATP, and NADPH roles in synthesis
• Regulation of fatty acid synthesis by insulin, glucagon, and epinephrine
• Adipose tissue lipolysis, plasma FFA transport, FFA uptake, fatty acid activation, and transport to mitochondria
• Mitochondrial fatty acid oxidation steps (beta-oxidation) details, and key enzymes that catalyze the formation of FADH₂ and NADH in each cycle
• Oxidation of palmitoyl-CoA yielding 106 ATPs
• Regulation of fatty acid oxidation
• Synthesis and utilization of ketone bodies

Additional Details:

• Many figures included were created by Lakshman Segar, Ph.D.
• Plasma lipoproteins: chylomicrons (CM), very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL)
• Plasma lipoprotein fractions are isolated using density-gradient ultracentrifugation
• Chylomicron structure: composed of triglycerides (TG), cholesterol esters (CE), phospholipids (PL), and apolipoproteins
• VLDL structure: composed of triglycerides (TG), cholesterol esters (CE), phospholipids (PL), and apolipoproteins
• LDL structure: primarily composed of cholesterol esters (CE) and apolipoproteins
• HDL structure: Primarily composed of protein and some lipids
• Composition of Plasma Lipoproteins: Detailed table provides size, density, percentage of protein, and lipid components for different lipoproteins. Includes sources like intestine, liver, VLDL, etc.
• Structure of lipoproteins: Detailed diagram of lipoprotein composition: core of nonpolar lipids (e.g., triglycerides, cholesterol esters), surface monolayer of amphipathic lipids (e.g., phospholipids, cholesterol), and various apolipoproteins.
• Fatty acid esters are mostly triglycerides (TAG), cholesterol esters (CE), and phospholipids (PL) that circulate in lipoproteins
• Free fatty acids (FFA) are mostly bound to albumin in plasma

Additional Information:

• Dietary lipids (fat): Digestive products, Absorption by intestinal mucosal cells
• Resynthesis TAG: formation of CHYLOMICRONS in enterocytes
• Secretion CHYLOMICRONS: into lacteals and thoracic ducts, systemic circulation
• Utilization CHYLOMICRONS: role of HDL and lipoprotein lipase, metabolism = degradation and synthesis
• Anatomical considerations of lipid digestion: includes the components and functions of liver, gallbladder, pancreas, lacteals, stomach, duodenum, jejunum, and ileum
• Dietary lipids are needed to obtain essential fats, structural lipids, and triacylglycerols
• Important fatty acids: various structures and their physiological importance, including essential fatty acids
• Formation of chylomicrons from dietary lipids (exogenous lipids): Triglycerides, cholesterol ester, phospholipids, and various apolipoproteins are the constituents.
• Lipid digestion products + bile salts + fat-soluble vitamins
• Absorption of lipids: contained in mixed micelles by enterocytes
• Lipid digestion and resynthesis in enterocytes : detailed diagram showing the steps in the process
• Utilization of CHYLOMICRONS (role of HDL and lipoprotein lipase): detailed diagram outlining the metabolic pathways involved.
• Orlistat: FDA-approved anti-obesity drug that inhibits gastric and pancreatic lipases. Decreases fat absorption

Additional Sections:

• Hepatic lipogenesis and VLDL formation: Detailed diagram of the biosynthetic pathway for lipids from sugars, liver's role, and the formation of Very Low Density Lipoproteins (VLDL), flow through the liver and into the blood
• Fate of VLDL: Role of HDL and lipoprotein lipase. Detailed diagram of VLDL breakdown, including enzymes and transport/endocytosis/receptor binding details in tissues
• Fatty acid synthesis (FAS): Conversion of glucose to cytosolic acetyl CoA. Role of citrate lyase and malic enzyme. NADPH production
• Regulation of acetyl CoA carboxylase (ACC): by citrate, protein/enzyme phosphorylation, and acyl-CoA/palmitoyl-CoA. Details of how regulation occurs through the activation and inactivation of the enzyme, the specific role of each component
• Regulation of acetyl-CoA carboxylase (ACC): by phosphorylation/dephosphorylation. Roles of insulin, epinephrine, and glucagon in regulation.
• Inhibition of carnitine palmitoyltransferase I (CPT I) by ↑malonyl-CoA. Detailed diagram illustrating the blockades and consequences of malonyl-CoA on CPT I function in fatty acid oxidation.
• Regulation of Fatty Acid Synthesis
• Regulation of Fatty Acid Oxidation
• Fatty Acid Synthase Multienzyme Complex: Diagram illustrating the various enzymatic components in the complex, including regions like malonyl/acetyl transacetylase, ketoacyl reductase, and thioesterase regions
• Biosynthesis of long-chain fatty acids : Detailed diagram of the complete process in both normal and synthetic pathways
• Microsomal elongase system for fatty acid chain elongation: Detailed diagram of the elongation of fatty acid chains
• Biosynthesis of glycerol-3-phosphate in liver vs adipose tissue: Differences between the two processes in the cells outlined.
• Synthesis of triacylglycerol (TAG): Detailed diagram summarizing the entire process from substrate to end product
• Adipose tissue lipolysis and FFA mobilization : Detailed diagram showing the steps involved in the breakdown of TAGs into glycerol and fatty acid monomers
• Overview of mitochondrial long-chain fatty acid oxidation : Detailed diagram outlining all steps in sequence, including transporters, coenzymes, and the role of the TCA cycle in the entire process
• Activation of fatty acid by fatty acyl-CoA synthetase enzyme: Illustration of the mechanisms in the activation of fatty acids to form acyl-CoA monomers
• Major metabolic routes for long-chain fatty acyl CoA: Diagram showing different metabolic routes (oxidation, storage, energy use)
• Structure of fatty acylcarnitine: Chemical structure of a fatty acyl carnitine molecule
• Transport of long-chain fatty acids into mitochondria: illustrated diagram of the carnitine shuttle
• Overview of B-oxidation : Steps outlined to illustrate the successive removal of acetyl-CoA from the fatty acid chain
• Oxidation of fatty acids with an odd number of carbon atoms: Illustrative diagram demonstrating how the oxidation of an odd-numbered carbon chain fatty acid produces different substrates for metabolism
• ATP generation from complete oxidation of palmitate (C16): Calculation of ATP produced from the full oxidation of palmitate
• Regulation of B-oxidation: Regulation of the entire process through different cellular signals, including insulin, glucagon, and AMP-activated protein kinase
• Formation, utilization, and excretion of ketone bodies: Diagram outlining the process of synthesis, transport, and utilization in extrahepatic tissues
• Transport of ketone bodies from the liver: Detailed diagram and explanation of the pathway for transporting ketone bodies from the liver to extrahepatic tissues. This includes the different enzymes and their mechanisms.
• Regulation of ketogenesis: Overview and diagrams illustrating the regulation of pathways involved in ketogenesis, covering different steps such as lipolysis, fatty acid activation, and β-oxidation in the liver.