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.