Lipid Metabolism Summary

Lipids Module Overview

  • Lipids1 – Structure & Classes: April 16
  • Lipids2 – Membranes and Membrane Transport: April 18
  • Lipids3 - Dietary Digestion: April 21
  • Lipids4 - Metabolism: April 23
  • Lipids5 – Fatty Acid Synthesis: April 25
  • Lipids6 - Cholesterol & Steroids: April 28
  • Lipids7 – Ketone Bodies: April 30
  • Lipids8 - Signal Transduction: Insulin & Glucagon May 2

Metabolism Review

  • Molecules are "burned up" via complex chemical processes.
  • Combustion of simple molecules generates energy (catabolism).
  • Metabolic pathways share intermediates (e.g., Acetyl CoA).
  • Cellular respiration converts carbon fuels into CO<em>2CO<em>2 and H</em>2OH</em>2O to generate energy (ATP).

Preparing for Metabolism

  • Lipolysis is involved if stored triacylglycerols supply fatty acids.
  • Hormones epinephrine and glucagon induce lipases.
  • Shorter chains and more unsaturated fatty acids are used first.
  • Carbon fuel is transported from adipose tissue by globular protein albumin.
  • Fatty acids use FABPs to enter muscle cells.

β-oxidation Pathway

  • Occurs in the cytoplasm of prokaryotes and the mitochondria of muscle cells.
  • Consists of four repeating steps:
    1. Oxidation by FAD
    2. Hydration
    3. Oxidation by NAD+NAD^+
    4. Thiolysis by coenzyme A
  • Each round shortens the fatty acid's hydrocarbon chain by 2 carbons.
  • Generates products that enter cellular respiration.

Acyl CoA Activation and Transport

  • Bringing fatty acids into mitochondria requires activation and channels.
  • Activation is achieved by attaching a fatty acid to coenzyme A (HS-CoA), catalyzed by acyl CoA synthetase.
  • The reaction is reversible but driven forward by ATP hydrolysis.
  • Acyl CoA crosses the outer mitochondrial membrane (OMM) via an ion channel.

Carnitine in Acyl Transport

  • 95% of carnitine is located within skeletal muscles.
  • Activities at this channel are the rate-limiting step.

β-oxidation Pathway Steps

  • Step 1: Oxidation by FAD
    • Enzyme: Acyl CoA dehydrogenase
    • Products: trans-Δ2-enoyl CoA and FADH2FADH_2
  • Step 2: Hydration
    • Enzyme: Enoyl CoA hydratase
    • Product: L-3-hydroxyacyl CoA
  • Step 3: Oxidation by NAD+NAD^+
    • Enzyme: L-3-hydroxyacyl CoA dehydrogenase
    • Products: 3-ketoacyl CoA and NADH
  • Step 4: Thiolysis by coenzyme A
    • Enzyme: β-ketothiolase
    • Products: acetyl CoA and a fatty acid chain two carbons shorter

Product Fate

  • Acetyl CoA can enter the citric acid cycle to generate ATP.
  • NADH and FADH2FADH_2 can donate electrons to the electron-transport chain.
  • The shortened fatty acid (acyl group) continues to be metabolized via β-oxidation.
  • Final thiolysis products for an even chain fatty acid: two acetyl CoA.

Odd Chain Fatty Acids

  • Final thiolysis products: acetyl CoA and propionyl CoA (a 3-carbon molecule).
  • Propionyl CoA is converted into succinyl CoA, which can enter the citric acid cycle.

Complex Fatty Acids

  • Very long chain fatty acids (22 or more carbons) are sent to the peroxisome first, shortened via peroxisomal β-oxidation, then transported to mitochondria.
  • Unsaturated fatty acids require additional enzymes to shift the position and configuration of the carbon-carbon double bond(s).

Regulation of β-oxidation

  • Steps 1-3 are controlled via feedback inhibition.
  • Influenced by NADH and acetyl CoA (suppress activity), PGC-1α (activates transcription factors), and cytoplasmic malonyl-CoA (suppresses activity).

Glycerol Metabolism

  • Liberated from triacylglycerols during dietary lipid digestion and lipolysis.
  • Sent to the liver, where it is phosphorylated by glycerol kinase.
  • The product is then oxidized and isomerized into glyceraldehyde 3-phosphate.
  • The molecule is directed into glycolysis (generate ATP) or gluconeogenesis (generate glucose), depending on the cell’s needs.