Lipid Metabolism Flashcards

Lipid Metabolism

Overview

• Lipid metabolism involves triacylglycerols, fatty acids, cholesterol, and lipoproteins.
• Konrad Bloch won the 1964 Nobel Prize for discoveries concerning cholesterol and fatty acid metabolism.

Functions of Lipids

• Energy metabolism.
• Membrane constituents.
• Hormones.
• Fat-soluble vitamins.
• Thermal insulators.
• Biological regulators.

Key Questions Addressed

• How are fats mobilized from dietary intake and adipose tissue?
• How are lipid molecules transported in the blood?
• How are fatty acids broken down and synthesized?
• How are unsaturated fatty acids oxidized and synthesized?
• What are ketone bodies, and what role do they play in metabolism?
• What are membrane lipids, sphingolipids, steroids, isoprenoids, and eicosanoids, and their function?

Triacylglycerols

• Also known as neutral fats.
• Characteristics are determined by their fatty acid composition.

Fatty Acids

• Examples include Capric, Lauric, Myristic, Palmitic, Stearic, Arachidic, Behenic, Lignoceric, and Cerotic acids (saturated).
• Unsaturated: Palmitoleic, Oleic, Linoleic, Linolenic, and Arachidonic acids.

Lipid Utilization and Transport

• Triacylglycerols (fats) serve as energy reserves.
• Fat has higher caloric content compared to carbohydrates.
• Oxidation of triacylglycerols yields 37 kJ/g, while carbohydrates/proteins yield 17 kJ/g.
• One gram of intracellular glycogen contains only 1/3 gram of anhydrous glucose polymer.
• Sources of triacylglycerols include diet, de novo biosynthesis, and adipocytes (storage).

Digestion and Absorption

• Bile salts act as emulsifiers.
• Lipids complex with proteins to form lipoproteins for transport through the blood and lymph.
• Lipid micelles are digested by pancreatic lipase.
• Triacylglycerols are resynthesized during absorption through intestinal mucosal cells.
• They are then packaged by lipoproteins (chylomicrons) for transportation into the lymph system.

Lipoproteins

• Major classes include Chylomicrons, VLDL, IDL, LDL, and HDL.
• Each has varying densities, protein, triacylglycerol, cholesterol, phospholipid, and apoprotein compositions.
• Examples of Apoproteins include A-I, A-II, B-48, B-100, C-I, C-II, C-III, D, and E, each with specific characteristics and functions.

Lipoprotein Transport

• Chylomicrons transport triacylglycerols from dietary fat to peripheral tissues.
• VLDL transports triacylglycerols from the liver to tissues.
• Glycerol and fatty acids are catabolized to generate energy or resynthesized into triacylglycerols in adipose tissue.

Cholesterol Transport

• LDL plays an important role in cholesterol homeostasis via receptor-mediated endocytosis.
• Oxidized or altered LDL is taken up by scavenger receptors, leading to foam cell formation and atherosclerosis.
• Intracellular cholesterol regulates its own level by controlling de novo biosynthesis, formation and storage of cholesterol esters, and LDL receptor density.
• Statins inhibit HMG-CoA reductase.

Mobilization of Stored Fat

• Release of fat from storage depots is controlled by hormones like glucagon and epinephrine through a cyclic AMP-mediated cascade system.

Cyclic AMP-Mediated Cascade System

• Involves hormone-receptor interaction, adenylate cyclase activation, cAMP production, activation of protein kinase, and activation of triacylglycerol lipase.
• Key enzymes: Adipose triacylglycerol lipase (ATGL), Hormone-sensitive lipase (HSL), and Monoacylglycerol lipase (MGL).

Fatty Acid Oxidation

• Franz Knoop discovered fatty acid β-oxidation.
• Fatty acids are oxidized stepwise, with initial attack on the β-carbon.
• ATP is essential; all intermediates are fatty acyl-CoAs.

Fatty Acid Activation and Transport into Mitochondria

• Involves fatty acyl-CoA ligases, adenylylation, and acylation.
• Fatty acyl-CoA is transferred to carnitine for transport through the mitochondrial inner membrane.

β-Oxidation Pathway

• Occurs in the mitochondrial matrix.
• Involves 4 cyclic reactions: Dehydrogenation, Hydration, Dehydrogenation, and Thiolytic cleavage.
• Each cycle shortens the fatty acyl-CoA by two carbons, producing FADH2, NADH, and acetyl-CoA.

Energy Yield from Fatty Acid Oxidation

• Palmitate oxidation yields a net of 106 ATP.
• ATP yield per carbon is higher for palmitic acid oxidation (6.62) compared to glucose glycolysis (5.0).

Oxidation of Unsaturated Fatty Acids

• Requires additional enzymes like Enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase.

Oxidation of Fatty Acids with Odd-Numbered Carbon Chain

• Catabolism of propionyl-CoA involves propionyl-CoA carboxylase, methylmalonyl-CoA epimerase, and methylmalonyl-CoA mutase (B12 coenzyme).

Control of Fatty Acid Oxidation

• Controlled by hormones (glucagon, epinephrine) via cyclic AMP cascade.
• Malonyl-CoA inhibits carnitine acyltransferase I, preventing fatty acyl-CoA entry into mitochondria.

Peroxisomal β-Oxidation of Fatty Acids

• Generates heat, not energy.
• Transfers electrons directly to oxygen.

α-Oxidation Pathway for Phytanic Acid Oxidation

• Defective in Refsum’s disease, leading to accumulation of phytanic acid.