Fatty Acids

Page 1: ATP Synthesis - Chemiosmotic Coupling

  • The mechanism of ATP synthesis involves chemiosmotic coupling.

  • Three sites during electron transport lead to the pumping of protons (H+) into the intermembrane space.

  • Increased proton concentration drives ATP synthase to alleviate the proton gradient.

  • Proton passage through ATP synthase leads to ATP generation.

ATP Synthase Structure

  • ATP synthase functions as:

    • A proton pore.

    • An ATP synthesizing enzyme.

  • Protons moving through this pore cause:

    • Rotation of the γ-subunit.

    • Conformational changes in β-subunits.

    • These changes facilitate ATP synthesis.

ATP Synthase Mechanism

  • Reiteration of ATP synthase functionality:

    • Protons through the pore rotate γ-subunit.

    • This results in conformational adjustments in β-subunits driving ATP synthesis.

  • ATP synthase has three functional states:

    • Open, Loose, Tight.

Visualization of ATP Synthase

  • A figure illustrates ATP synthase and related components including:

    • Actin filament, Avidin, Biotin.

    • Various ATP synthase functions.

    • Related resources for visual understanding of ATP synthase.

NADH Transport to Mitochondria

  • Cytoplasmic NADH from glycolysis cannot cross the mitochondrial membrane.

  • The malate-aspartate shuttle is utilized to transport NADH into the mitochondria.

ATP Yield from Glucose

  • Final energy yield from one glucose molecule:

    • 31 ATP (assuming 2.5 ATP from each NADH and 1.5 ATP from FADH).

    • ΔGo’ for glucose oxidation: -2870 kJ/mol.

    • ΔGo’ for ATP hydrolysis: -30.5 kJ/mol.

    • Efficiency of ATP conversion: 32%.

Fat Storage vs Glycogen

  • About 2-3% of human energy is stored as glycogen/glucose, while most is stored as fat.

  • Fats are more reduced than sugars, holding more energy (38 kJ/g for fats vs. 16 kJ/g for sugars).

  • Storing energy as sugar rather than fat would significantly increase body weight, illustrating the efficiency of fat storage.

Fatty Acids Overview

  • Fatty acids are carboxylic acids linked to an aliphatic hydrocarbon chain.

  • They exhibit amphiphilic properties and can be:

    • Saturated (no double bonds) or

    • Unsaturated (contains double bonds).

Unsaturated Fatty Acids

  • Orientation around carbon double bonds determines if the fatty acid is:

    • Cis (hydrogens on the same side)

    • Trans (hydrogens on opposite sides).

Common Fatty Acids

  • Table detailing naturally occurring fatty acids including:

    • Carbon number, common name, systematic name, melting point, and solubility.

  • Examples include:

    • Lauric acid (C12:0), Myristic acid (C14:0), Palmitic acid (C16:0).

Triacylglycerols Explained

  • Triacylglycerols serve as the polymeric storage form of fatty acids.

  • They consist of three fatty acid chains esterified to glycerol.

  • These compounds are mobilized to release fatty acids for ATP synthesis.

Lipase Action on Triacylglycerols

  • Triacylglycerols are hydrolyzed to fatty acids and glycerol by lipases.

  • The reaction includes:

    • Lipase catalyzing the process with water to produce fatty acids and glycerol.

Fatty Acid Sources for Energy

  • Fatty acids for energy metabolism originate from:

    • Dietary triacylglycerols,

    • Triacylglycerols synthesized in the liver,

    • Stored triacylglycerols in adipocytes.

Absorption of Dietary Triacylglycerols

  • Dietary triacylglycerols are absorbed in the small intestine, then remade into triacylglycerols and complexed with lipoproteins (chylomicrons).

  • These are distributed to cells, broken down by lipoprotein lipase, and utilized for energy or storage in adipose tissue.

Activation of Fatty Acids

  • Fatty acids enter muscle cytoplasm and are activated with Coenzyme A as Acyl-CoA for mitochondrial catabolism.

Transport to Mitochondria - Carnitine Linkage

  • Fatty acids achieve mitochondrial entry via a carnitine linkage through carnitine acyltransferase I (CPT I).

  • Inside, carnitine acyltransferase II (CPT II) regenerates Acyl-CoA from acyl-carnitine.

Fatty Acid Catabolism - β-Oxidation

  • Fatty acids catabolized via β-oxidation remove two carbons at a time, yielding:

    • Acetyl CoA (to citric acid cycle),

    • FADH2 and NADH.

Further β-Oxidation Processes

  • Continued focus on β-oxidation process, emphasizing the generation of Acetyl CoA, FADH2, and NADH in each cycle.

β-Oxidation and Citric Acid Cycle Similarities

  • The first three steps of β-oxidation mirror those of the citric acid cycle in their sequential order of reactions.

ATP Yield Calculation for Fatty Acids

  • Yield of ATP from oxidation of Palmitoyl-CoA includes:

    • 7 FADH2 (10.5 ATP).

    • 7 NADH (17.5 ATP).

    • Total ATP output calculated as 108 ATP.

Odd-Numbered Fatty Acid Catabolism

  • Rare occurrence of β-oxidation of fatty acids with odd carbon numbers;

  • Propionyl-CoA converted to succinyl CoA, entering the citric acid cycle (requires vitamin B12 for the enzyme).

Substrates for Fatty Acid Synthesis

  • Malonyl-CoA is a primary substrate for fatty acid synthesis, produced by acetyl-CoA carboxylase using biotin cofactor.

Fatty Acid Synthesis Overview

  • Fatty acid synthesis is performed by fatty acid synthase (FAS), complex and structure varies between yeast and mammals.

  • ACP plays a crucial role, swinging substrates for efficient enzymatic activity.

Comparison of ACP and CoA

  • Comparison of Phosphopantetheine group in Acyl Carrier Protein (ACP) and Coenzyme A (CoASH).

Fatty Acid Synthesis Reaction Scheme

  • Involves reduction steps by NADPH to create fatty acyl-CoA in yeast, and free fatty acids in humans.

Fatty Acid Synthesis vs Breakdown

  • Key differences include:

    • Fatty acids built on ACP vs. CoA.

    • All synthesized fatty acids are palmitate.

    • NADPH as the primary reducing agent.

Mitochondrial Acetyl-CoA to Cytoplasm

  • Mechanism needed for transporting mitochondrial Acetyl-CoA to the cytoplasm.

Interrelationship of Fatty Acid Metabolism

  • Illustration of metabolism relationships emphasizing hormonal regulation (insulin vs. glucagon) and substrate availability for fatty acid synthesis.

Lipid Transport in Blood

  • Overview of lipid transport mechanisms:

    • Chylomicrons (transport dietary triacylglycerols).

    • VLDL (carries liver-synthesized triacylglycerols).

    • LDL (bad cholesterol, carrying from liver to tissue).

    • HDL (good cholesterol, collects cholesterol for return to liver).