Nuclear Medicine-Biochem-Lipid metabolism

Lipid Metabolism Overview

• Instructor: Juliana Antonipillai, PhD, RMIT University

Outline of Topics

1. Lipid Classification, Structure, and Functions

2. Oxidation of Fatty Acids

3. Synthesis of Fatty Acids

4. Synthesis of Triglycerides, Phospholipids, Cholesterol, and Formation of Ketone Bodies in the Liver

Objectives of Lipid Metabolism Study

• Understand different classifications of lipids and their structures and roles.

• Describe reactions involved in fatty acid oxidation.

• Calculate the total number of ATP produced during fatty acid oxidation.

• Outline reactions for fatty acid synthesis.

• Outline synthesis of triglycerides and phospholipids.

• Discuss cholesterol synthesis.

• Describe reactions during ketone body formation in the liver.

1. Lipid Classification, Structure, and Functions

Types of Lipids

• Fatty Acids: Components of triglycerides and phospholipids.

• Triglycerides: Storage form of fatty acids.

• Phospholipids: Major component of cell membranes, amphipathic.

• Glycolipids: Components of cell membranes with carbohydrate groups.

• Steroids: Include cholesterol, critical for membrane fluidity.

Fatty Acids

• Vary in length and saturation.

• Saturated: All single bonds.

• Unsaturated: Contains double bonds (Cis and Trans).

• Examples include Arachidic acid (20 C), Palmitic acid (16 C), Oleic acid (monounsaturated).

Structure of Fatty Acids

• Carboxylic Acid Head: Hydrophilic, reactive, ionized in solution.

• Hydrocarbon Tail: Hydrophobic, chemically inert, responsible for separation from water.

• Fatty acids can vary in their chain length and number of double bonds.

Triglycerides (Triacylglycerols)

• Composed of three fatty acids linked to glycerol.

• Solid at room temperature: fats; liquid at room temperature: oils.

• Nonpolar and hydrophobic properties.

2. Oxidation of Fatty Acids

Metabolism Overview

• Breakdown of triglycerides to provide fatty acids and glycerol.

• Fatty acid oxidation occurs in three main stages:

  1. Mobilization of fatty acids.

  2. Transport into the mitochondria.

  3. β-Oxidation cycle occurring in mitochondrial matrix.

Stages of Fatty Acid Oxidation

1. Mobilization: Hormonal control mobilizes fatty acids bound to albumin from adipocytes.

2. Transport: Fatty acids converted to Acyl-CoA, requiring carnitine for mitochondrial membrane transport.

3. β-Oxidation Cycle: Consists of four consecutive reactions - oxidation, hydration, another oxidation, and cleavage.

Key Reactions in β-Oxidation

• Oxidation to Enoyl-CoA: FAD reduces to FADH2.

• Hydration: Water adds, forming a hydroxyl group.

• Further Oxidation: Hydroxyl group oxidized to form keto group.

• Cleavage: Acetyl-CoA is released and fatty acyl-CoA is shortened for repeated cycles.

ATP Yield from Fatty Acid Oxidation

• Example: Palmitic Acid (C16) oxided through 7 cycles yields 8 Acetyl-CoA, 7 FADH2, 7 NADH with net ATP generation calculated accordingly.

3. Synthesis of Fatty Acids

Process Overview

• 3 Stages: 1) Acetyl CoA transport to cytoplasm, 2) Conversion to Malonyl CoA, 3) Fatty Acid Synthase elongation cycle.

Reactions in Fatty Acid Synthesis

1. Condensation: Acetyl-CoA and malonyl-CoA form acetoacetyl-ACP.

2. Reduction: Acetoacetyl-ACP to β-Hydroxybutyryl-ACP using NADPH.

3. Dehydration: β-Hydroxybutyryl-ACP to unsaturated-ACP with water loss.

4. Final Reduction: Unsaturated-ACP reduced to butyryl-ACP, allowing further condensation for elongation.

Synthesis of Palmitate (C16)

• Requires 7 cycles, utilizing Malonyl CoA as a 2C donor, yielding Palmitate and necessary cofactors.

4. Synthesis of Triglycerides, Phospholipids, Cholesterol and Ketone Bodies

Synthesis of Triglycerides

• Glycerol-3-phosphate reacts with fatty acids to create diacylglycerol leading to triglyceride formation.

Synthesis of Phospholipids

• Involves similar pathways to triglyceride synthesis but leads to diverse end products like Phosphatidylinositol, Phosphatidylcholine, etc.

Cholesterol Synthesis

• Occurs mainly in the liver in three stages, from 3 Acetyl-CoA to Squalene, and subsequently to cholesterol.

Ketone Body Formation

• High rates of fatty acid oxidation cause excess Acetyl-CoA to form ketone bodies, significant in conditions such as starvation or diabetes.

• Impact on health can lead to complications such as coma or death.