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 37kJ/g37 kJ/g, while carbohydrates/proteins yield 17kJ/g17 kJ/g.
  • One gram of intracellular glycogen contains only 1/31/3 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.