Fatty Acid Degradation and Synthesis

Fatty Acid Degradation and Synthesis

• Fatty acids are a major fuel source.
• Fatty acid degradation breaks down fatty acids (long-chain hydrocarbons) into acetyl CoA.
• Fatty acid degradation occurs in the mitochondrial matrix.
• The breakdown of fatty acids into Acetyl CoA is via Beta-oxidation.
• Beta oxidation involves 4 steps (dehydrogenation, hydration, dehydrogenation, thiolysis) that shorten a fatty acid by two carbons.
• Each cycle produces 1 FADH₂ and 1 NADH, and 1 Acetyl CoA.
• Acetyl CoA produced further metabolized in TCA and ETC (Electron transport chain) to generate ATP.

Fatty Acid Significance

• Fatty acids are building blocks for phospholipids and glycolipids.
• Fatty acids bind proteins to membranes.
• Fatty acid derivatives are used as hormones and intracellular messengers.
• Fatty acids also act as a high energy fuel source.
• Fatty acids along with glycerol forms storage molecule triacylglycerols (TAG).
• TAG is used for storing fatty acids for energy.

Triacylglycerols (TAGs)

• TAGs are made of three fatty acids ester bonded to glycerol.
• TAGs are a highly concentrated store of energy.
• 9kcal/g of TAGs vs 4kcal/g glycogen
• Glycogen is highly hydrated (2g H₂O/g glycogen)
• TAGs are stored anhydrously
• Body has a near infinite capacity to store TAGs.

Utilization of TAGs as Fuel

• Triacylglycerol degradation occurs in adipose tissue.
• TAGs get degraded into fatty acids and glycerol.
• Lipase converts triacylglycerol to di and then mono and then free glycerol.
• Free fatty acids are exported out of adipocytes and bind to albumin in blood where transported to tissues that need it.
• Fatty acid activation occurs in the cytosol before entering mitochondria.
• Fatty acid degradation (β-oxidation) occurs in the mitochondrial matrix.

Degradation of TAGs by Hormones

• Glucagon, Epinephrine, Norepinephrine, ACTH are hormones that controls TAG degradation.

Fate of Glycerol

• Free glycerol cannot be phosphorylated in adipocytes as they lack glycerol kinase.
• Glycerol is transported to liver where it get phosphorylated.
• Glycerol is reduced to DHAP (Dihydroxyacetone phosphate).
• DHAP can enter glycolysis or gluconeogenesis.
• ATP is used and NADH is synthesized.

Fatty Acid Activation and Transport

• Fatty acids are activated in the cytosol by addition of CoA to form (fatty) acyl CoA by enzyme acyl-CoA synthetase .
• Uses ATP and produces AMP.
• Once activated it crosses the mitochondrial membranes into the matrix with the aid of carnitine.

Fatty Acid Synthesis

• Glucose is the main source of carbon skeletons.
• In the fed state, excess amino acids can be used to make fatty acids via conversion to glucogenic intermediates, or directly to acetyl CoA.
• Fatty acid synthesis occurs in the cytosol.
• Synthesis of malonyl CoA (MCoA), a primer, from acetyl CoA (AcCoA) is needed in the cytosol.

Fatty Acid Synthesis is Energetically Expensive

• FA synthesis only occurs when there are high levels of citrate and ATP in the cytosol.
• ATP is required for the synthesis of malonyl CoA (primer).
• NADPH is required for the reduction of the carbon skeleton.
• Sources of NADPH are Pentose Phosphate Pathway and Conversion of oxaloacetate to pyruvate which exchanges NADH for NADPH

Ketogenesis

• Acetyl CoA generated from Beta-oxidation, is used by 2 processes: (1) TCA cycle & (2) Ketogenesis in the liver mitochondria.
• In animals, acetyl CoA is not used in the synthesis of glucose.
• In cases of starvation, in liver tissue oxaloacetate is used in gluconeogenesis, which depletes it.
• Without oxaloacetate, fatty acids are metabolized to produce ketone bodies.
• Ketone bodies are water soluble and are readily transported than fatty acids.
• Ketogenesis produces 3 ketone bodies: 1. Hydroxybutyrate, 2. Acetoacetate, 3. Acetone.
• Ketone bodies are transported into the blood and carried to extra-hepatic tissues (brain).

Some Amino Acids Can Be Used in Ketogenesis

• Some amino acids are glucogenic.
• Others are ketogenic, which can be used to synthesize ketone bodies or acetyl CoA.
• Some are both.
• Examples included: Isoleucine, Lysine, Phenylalanine, Threonine, Tyrosine.

Ketone Body Utilization

• In peripheral tissues, ketone bodies are reconverted to acetyl CoA and oxidized in the TCA cycle to produce energy.
• During prolonged fasting or starvation, fatty acids and ketone bodies can be used as fuel in most tissues except the liver to release energy.
• The liver lacks acetoacetate CoA transferase and therefore cannot use ketone bodies.
• Brain cannot use fatty acids and depends on ketone bodies for energy.

Summary

• Fatty acid degradation breaks fatty acids into acetyl coA.
• Degradation of TAGs occurs in adipose tissue and uses lipase.
• Fatty acids are activated to acyl CoA by the enzyme acyl-CoA synthetase and transported to matrix of mitochondria.
• Fatty Acid synthesis occurs in the cytosol.
• Acetyl CoA carboxylase is the key regulatory enzyme.
• Ketogenesis produces ketone bodies in the liver (hydroxybutyrate, acetoacetate, acetone).

Explore the processes of fatty acid degradation and synthesis in this quiz. Learn about the significance of fatty acids as fuel sources, their role in metabolism, and the various steps involved in beta-oxidation. Test your knowledge on how fatty acids contribute to various biological functions and energy storage.