Fatty Acid Synthesis in Eukaryotes
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Questions and Answers

Where does the catabolism of fatty acids take place?

  • Chloroplast
  • Endoplasmic reticulum
  • Mitochondria (correct)
  • Cytosol

    • What is required for the anabolism of fatty acids?

  • Reducing power from NADH+H+ and FADH2
  • Acetyl-CoA and malonyl-CoA (correct)
  • Malonyl-CoA and FADH2
  • Acetyl-CoA and NADH+H+

    • Where does fatty acid biosynthesis occur?

  • Only in cells with chloroplasts
  • In the cytosol of all cells
  • Only in cells with mitochondria
  • Every cell with mitochondria, but with different rates (correct)

    • What is the source of NADPH+H+ in adipocytes?

    <p>Pentose phosphate pathway and malic enzyme</p> Signup and view all the answers

    Where does fatty acid synthesis occur in animals?

    <p>Cytosol</p> Signup and view all the answers

    What is the product of fatty acid catabolism?

    <p>Acetyl-CoA and reducing power</p> Signup and view all the answers

    Where do plants typically store fat?

    <p>In seeds, nuts, and fruits</p> Signup and view all the answers

    How much fat does a typical 70-kg human have?

    <p>15 kg</p> Signup and view all the answers

    What is the backbone of triacylglycerides and phospholipids?

    <p>Glycerol</p> Signup and view all the answers

    What is the primary source of glycerol 3-phosphate in the synthesis of triacylglycerides and phospholipids?

    <p>Glycolysis</p> Signup and view all the answers

    Which enzyme is involved in the synthesis of glycerol 3-phosphate from glycerol?

    <p>Glycerol kinase</p> Signup and view all the answers

    What is the function of triacylglycerides in the body?

    <p>Energy storage</p> Signup and view all the answers

    What is the function of phospholipids in the body?

    <p>Cell membrane structure</p> Signup and view all the answers

    How long can a typical 70-kg human survive on stored fat?

    <p>12 weeks</p> Signup and view all the answers

    Where is acetyl-CoA made in nonphotosynthetic eukaryotes?

    <p>Mitochondria</p> Signup and view all the answers

    What is the energy cost of transporting acetyl-CoA from the mitochondria to the cytosol?

    <p>2 ATPs</p> Signup and view all the answers

    What is the source of acetate units in fatty acid synthesis?

    <p>Activated malonate</p> Signup and view all the answers

    What is the product of fatty acid synthesis catalyzed by FAS I in vertebrates?

    <p>Palmitate 16:0</p> Signup and view all the answers

    In which system are the active sites of fatty acid synthesis located in different domains within a single polypeptide chain?

    <p>FAS I</p> Signup and view all the answers

    What is the net ATP cost of fatty acid synthesis?

    <p>3 ATPs per 2C unit</p> Signup and view all the answers

    What is the reduction process involved in each pass of fatty acid synthesis?

    <p>Reduction of a carbonyl carbon to a methylene carbon</p> Signup and view all the answers

    What is the committed step of fatty acid synthesis?

    <p>The acetyl-CoA carboxylase reaction</p> Signup and view all the answers

    What is the primary function of triacylglycerides in the body?

    <p>To provide energy for the body</p> Signup and view all the answers

    Where does most glycerol 3-phosphate come from in the synthesis of triacylglycerides and phospholipids?

    <p>From dihydroxyacetone phosphate from glycolysis</p> Signup and view all the answers

    What is the backbone of triacylglycerides and phospholipids?

    <p>Glycerol</p> Signup and view all the answers

    In which cells is glycerol kinase absent?

    <p>Adipocytes</p> Signup and view all the answers

    How long can a typical 70-kg human survive on stored fat?

    <p>12 weeks</p> Signup and view all the answers

    What is the function of phospholipids in the body?

    <p>To provide structure for cell membranes</p> Signup and view all the answers

    Where do plants typically store fat?

    <p>In seeds, nuts, and fruits</p> Signup and view all the answers

    What is the significance of having triacylglycerides and phospholipids in the body?

    <p>They provide energy and structure for cell membranes</p> Signup and view all the answers

    What is the precursor for triacylglycerides and phospholipids?

    <p>Phosphatidic acid</p> Signup and view all the answers

    What is the advantage of making phosphatidic acid?

    <p>It can be made into triacylglycerol or phospholipid</p> Signup and view all the answers

    What is the effect of insulin on triacylglycerol synthesis?

    <p>Stimulation of triacylglycerol synthesis</p> Signup and view all the answers

    What is the result of lack of insulin on fatty acid metabolism?

    <p>Increased lipolysis</p> Signup and view all the answers

    What is the enzyme involved in the removal of the 3-phosphate from phosphatidic acid?

    <p>Phosphatidic acid phosphatase</p> Signup and view all the answers

    What is the product of the reaction catalyzed by phosphatidic acid phosphatase?

    <p>1,2-diacylglycerol</p> Signup and view all the answers

    What is the consequence of untreated diabetes on fat metabolism?

    <p>Increased rate of fat oxidation, resulting in weight loss</p> Signup and view all the answers

    What is the consequence of insulin deficiency on fatty acid synthesis?

    <p>Fatty acid synthesis is inhibited</p> Signup and view all the answers

    What percentage of free fatty acids released by lipolysis are reesterified to form TAGs?

    <p>75%</p> Signup and view all the answers

    What happens to glycolysis in adipocytes during lipolysis?

    <p>It is inhibited</p> Signup and view all the answers

    What is the source of glycerol 3-phosphate in the triacylglycerol cycle?

    <p>Glyceroneogenesis</p> Signup and view all the answers

    What is the fate of some free fatty acids released from adipose tissue?

    <p>They are transported to the liver and redeposited in adipose cells</p> Signup and view all the answers

    What is the primary function of the triacylglycerol cycle?

    <p>To store energy from fatty acids</p> Signup and view all the answers

    What is the role of glyceroneogenesis in the triacylglycerol cycle?

    <p>To generate glycerol 3-phosphate</p> Signup and view all the answers

    What is the name of the process by which some free fatty acids are recycled in adipose tissue?

    <p>Triacylglycerol cycle</p> Signup and view all the answers

    What is the precursor for glycerol 3-phosphate generation in the triacylglycerol cycle?

    <p>All of the above</p> Signup and view all the answers

    What percentage of free fatty acids released by lipolysis are reesterified to form TAGs?

    <p>75%</p> Signup and view all the answers

    What happens to glycolysis in adipocytes during lipolysis?

    <p>It is inhibited</p> Signup and view all the answers

    What is the fate of some free fatty acids released from adipose tissue?

    <p>They are transported to the liver, remade into TAG, and redeposited in adipose cells</p> Signup and view all the answers

    What is the primary function of the triacylglycerol cycle?

    <p>To recycle fatty acids released from adipose tissue</p> Signup and view all the answers

    What is the role of glyceroneogenesis in the triacylglycerol cycle?

    <p>To convert pyruvate to DHAP</p> Signup and view all the answers

    What is the name of the process by which some free fatty acids are recycled in adipose tissue?

    <p>Triacylglycerol cycling</p> Signup and view all the answers

    Where does glyceroneogenesis occur?

    <p>In both the liver and adipose tissue</p> Signup and view all the answers

    What is the source of glycerol 3-phosphate in the triacylglycerol cycle?

    <p>Glyceroneogenesis</p> Signup and view all the answers

    What is the primary source of glycerol 3-phosphate in the synthesis of triacylglycerides and phospholipids?

    <p>Dihydroxyacetone phosphate from glycolysis</p> Signup and view all the answers

    What is the backbone of triacylglycerides and phospholipids?

    <p>Glycerol</p> Signup and view all the answers

    In which cells is glycerol kinase absent?

    <p>Adipocytes</p> Signup and view all the answers

    How long can a typical 70-kg human survive on stored fat?

    <p>12 weeks</p> Signup and view all the answers

    What is the function of triacylglycerides in the body?

    <p>Energy storage</p> Signup and view all the answers

    What is the function of phospholipids in the body?

    <p>Cell membrane structure</p> Signup and view all the answers

    Where do plants typically store fat?

    <p>Seeds, nuts, and fruits</p> Signup and view all the answers

    What is the significance of having triacylglycerides and phospholipids in the body?

    <p>For both energy storage and cell membrane structure</p> Signup and view all the answers

    What is the precursor for triacylglycerides and phospholipids?

    <p>Phosphatidic acid</p> Signup and view all the answers

    What is the advantage of making phosphatidic acid?

    <p>It can be made into either triacylglycerol or phospholipid</p> Signup and view all the answers

    What is the effect of insulin on triacylglycerol synthesis?

    <p>It stimulates triacylglycerol synthesis</p> Signup and view all the answers

    What is the result of lack of insulin on fatty acid metabolism?

    <p>Increased lipolysis and fatty acid oxidation</p> Signup and view all the answers

    What is the enzyme involved in the removal of the 3-phosphate from phosphatidic acid?

    <p>Phosphatidic acid phosphatase (lipin)</p> Signup and view all the answers

    What is the product of the reaction catalyzed by phosphatidic acid phosphatase?

    <p>1,2-Diacylglycerol</p> Signup and view all the answers

    What is the consequence of untreated diabetes on fat metabolism?

    <p>Increased fat oxidation and weight loss</p> Signup and view all the answers

    What is the consequence of insulin deficiency on fatty acid synthesis?

    <p>Decreased fatty acid synthesis</p> Signup and view all the answers

    What is the byproduct of fatty acid catabolism that is used to produce ATP?

    <p>FADH2</p> Signup and view all the answers

    In which cellular compartment does fatty acid synthesis occur in animals?

    <p>Cytosol</p> Signup and view all the answers

    What is the role of pentose phosphate pathway in fatty acid synthesis?

    <p>Generation of NADPH+H+</p> Signup and view all the answers

    What is the source of acetyl-CoA in fatty acid synthesis?

    <p>Mitochondria</p> Signup and view all the answers

    What is the reducing power required for fatty acid synthesis?

    <p>NADPH+H+</p> Signup and view all the answers

    In which cellular compartment does the anabolism of fatty acids occur in plants?

    <p>Chloroplast</p> Signup and view all the answers

    What is the cost of transporting acetyl-CoA from the mitochondria to the cytosol for fatty acid synthesis?

    <p>2 ATPs</p> Signup and view all the answers

    What is the product of fatty acid synthesis catalyzed by FAS I in vertebrates?

    <p>Palmitate 16:0</p> Signup and view all the answers

    What is the reduction process involved in each pass of fatty acid synthesis?

    <p>Reduction of a carbonyl carbon to a methylene carbon</p> Signup and view all the answers

    What is the source of acetate units in fatty acid synthesis?

    <p>Malonyl-CoA</p> Signup and view all the answers

    What is the committed step of fatty acid synthesis?

    <p>The acetyl-CoA carboxylase reaction</p> Signup and view all the answers

    What is the net ATP cost of fatty acid synthesis?

    <p>3 ATPs per 2C unit</p> Signup and view all the answers

    What is the function of FAS II in plants and bacteria?

    <p>To produce a variety of fatty acid products</p> Signup and view all the answers

    How many active sites are present in the FAS I complex in vertebrates?

    <p>7</p> Signup and view all the answers

    What is the primary source of glycerol 3-phosphate in the synthesis of triacylglycerides and phospholipids?

    <p>Dihydroxyacetone phosphate (DHAP) from glycolysis</p> Signup and view all the answers

    Which enzyme is absent in adipocytes?

    <p>Glycerol kinase</p> Signup and view all the answers

    What is the function of triacylglycerides in the body?

    <p>To store energy for fuel</p> Signup and view all the answers

    What is the significance of having triacylglycerides and phospholipids in the body?

    <p>To provide energy and structure to cell membranes</p> Signup and view all the answers

    What is the precursor for triacylglycerides and phospholipids?

    <p>Glycerol 3-phosphate</p> Signup and view all the answers

    In which cells is fatty acid synthesis primarily occurring?

    <p>Adipocytes</p> Signup and view all the answers

    What is the advantage of making phosphatidic acid?

    <p>It is a precursor for triacylglycerides and phospholipids</p> Signup and view all the answers

    What is the fate of some free fatty acids released from adipose tissue?

    <p>They are reesterified to form TAGs</p> Signup and view all the answers

    What is the role of ACP in fatty acid synthesis?

    <p>To carry intermediates from one enzyme subunit to the next</p> Signup and view all the answers

    What is the overall goal of fatty acid synthesis?

    <p>To attach acetate units to a growing chain and then reduce it</p> Signup and view all the answers

    What is the prosthetic group covalently attached to ACP?

    <p>4'-phosphopantetheine</p> Signup and view all the answers

    What is the first step in charging?

    <p>Addition of Acetyl-CoA to ACP</p> Signup and view all the answers

    What is the function of β-ketoacyl-ACP synthase (KS)?

    <p>To catalyze the condensation of the growing chain with activated acetate</p> Signup and view all the answers

    How many enzyme-catalyzed steps are involved in each cycle of fatty acid synthesis?

    <p>4</p> Signup and view all the answers

    What is the initial attachment of the growing chain to the enzyme?

    <p>Thioester linkage</p> Signup and view all the answers

    What is the purpose of the flexible arm in ACP?

    <p>To tether the acyl chain while carrying intermediates from one enzyme subunit to the next</p> Signup and view all the answers

    What is the role of acyl-CoA synthetase in the synthesis of phosphatidic acid?

    <p>To activate fatty acids for acyl transferase reaction</p> Signup and view all the answers

    What is the advantage of making phosphatidic acid?

    <p>It can be made into either triacylglycerol or phospholipid</p> Signup and view all the answers

    What is the result of phosphatidic acid phosphatase (lipin) activity?

    <p>Removal of the 3-phosphate from phosphatidic acid</p> Signup and view all the answers

    What is the effect of insulin on triacylglycerol synthesis?

    <p>Stimulation of triacylglycerol synthesis</p> Signup and view all the answers

    What is the purpose of using activated malonyl groups in fatty acid synthesis?

    <p>To make the reaction energetically favorable</p> Signup and view all the answers

    What is the consequence of insulin deficiency on fatty acid metabolism?

    <p>Increased fatty acid oxidation</p> Signup and view all the answers

    What is the product of the reaction catalyzed by phosphatidic acid phosphatase?

    <p>1,2-Diacylglycerol</p> Signup and view all the answers

    What is the result of the coupling of condensation to decarboxylation of malonyl-CoA?

    <p>The reaction becomes energetically favorable</p> Signup and view all the answers

    What is the consequence of untreated diabetes on fat metabolism?

    <p>Increased rates of fat oxidation, leading to weight loss</p> Signup and view all the answers

    What is the role of β-ketoacyl-ACP reductase in fatty acid synthesis?

    <p>To reduce β-ketoacyl-ACP</p> Signup and view all the answers

    What is the product of the reaction catalyzed by β-hydroxyacyl-ACP dehydratase?

    <p>trans-Δ2-Enoyl-ACP</p> Signup and view all the answers

    What is the precursor molecule for both triacylglycerol and phospholipid synthesis?

    <p>Phosphatidic acid</p> Signup and view all the answers

    What is the advantage of using activated acetate in fatty acid degradation?

    <p>It makes the reaction energetically favorable</p> Signup and view all the answers

    What is the significance of the reversal of fatty acid synthesis and degradation in the cell?

    <p>It makes both processes energetically favorable</p> Signup and view all the answers

    What is the role of β-ketoacyl-ACP synthase in fatty acid synthesis?

    <p>To condense malonyl-CoA with ACP</p> Signup and view all the answers

    What is the purpose of charging in fatty acid synthesis?

    <p>To add malonyl-CoA to ACP</p> Signup and view all the answers

    What percentage of free fatty acids released by lipolysis are reesterified to form TAGs?

    <p>75%</p> Signup and view all the answers

    What is the primary function of the triacylglycerol cycle?

    <p>To recycle fatty acids back to adipose tissue</p> Signup and view all the answers

    What happens to glycolysis in adipocytes during lipolysis?

    <p>It is inhibited</p> Signup and view all the answers

    What is the source of glycerol 3-phosphate in the triacylglycerol cycle?

    <p>Glyceroneogenesis</p> Signup and view all the answers

    What is the fate of some free fatty acids released from adipose tissue?

    <p>They are reesterified to form TAGs</p> Signup and view all the answers

    What is the role of glyceroneogenesis in the triacylglycerol cycle?

    <p>To generate glycerol 3-phosphate</p> Signup and view all the answers

    What is the name of the process by which some free fatty acids are recycled in adipose tissue?

    <p>Triacylglycerol cycle</p> Signup and view all the answers

    What is the precursor for glycerol 3-phosphate generation in the triacylglycerol cycle?

    <p>Pyruvate</p> Signup and view all the answers

    What is the precursor for phosphatidylserine synthesis?

    <p>Phosphatidyl-ethanolamine</p> Signup and view all the answers

    What is the central role of phospholipids in?

    <p>Signal transduction</p> Signup and view all the answers

    What is the function of phospholipids in the processes of?

    <p>Endocytosis, phagocytosis, and macropinocytosis</p> Signup and view all the answers

    What is the significance of the salvage pathway in the synthesis of phosphatidylserine and phosphatidylcholine?

    <p>It is a complementary pathway for phospholipid synthesis</p> Signup and view all the answers

    What is the property of phospholipids that makes them anti-inflammatory?

    <p>Their structure and composition</p> Signup and view all the answers

    Which of the following lipids uses similar pathways used for phospholipid synthesis?

    <p>Ether lipids</p> Signup and view all the answers

    Study Notes

    Acetyl-CoA Transport and Fatty Acid Synthesis

    • In non-photosynthetic eukaryotes, acetyl-CoA is made in the mitochondria and transported into the cytosol for fatty acid synthesis at a cost of 2 ATPs.
    • The total cost of fatty acid synthesis is 3 ATPs per 2C unit, which is approximately 50% of the NADPH+H+ units necessary for fatty acid biosynthesis.

    Overview of Fatty Acid Synthesis

    • Fatty acids are synthesized in several passes, with each pass involving the reduction of a carbonyl carbon to a methylene carbon.
    • The acetate unit for fatty acid synthesis comes from activated malonate in the form of malonyl-CoA.

    The Acetyl-CoA Carboxylase Reaction

    • The acetyl-CoA carboxylase reaction is the committed step in fatty acid synthesis.

    Fatty Acid Synthase (FAS)

    • FAS I is a single polypeptide chain with 7 active sites in vertebrates, leading to a single product: palmitate (16:0).
    • FAS II is a separate enzyme system in plants and bacteria, producing a variety of fatty acid products (saturated, unsaturated, branched, etc.).

    Synthesis of Fat (Triacylglycerides) and Phospholipids

    • Animals and plants store fat (triacylglycerides) for fuel.
    • The typical 70-kg human has approximately 15 kg of fat, which can last for 12 weeks.
    • Animals, plants, and bacteria make phospholipids for cell membranes.
    • Both molecules contain a glycerol backbone and 2 (phospholipids) or 3 (triacylglycerides) fatty acids.

    Synthesis of Backbone of TAGs and Phospholipids

    • Most glycerol 3-phosphate comes from dihydroxyacetone phosphate (DHAP) via glycerol 3-phosphate dehydrogenase.
    • Some glycerol 3-phosphate is made from glycerol via glycerol kinase (minor pathway in liver and kidney, absent in adipocytes).

    Catabolism and Anabolism of Fatty Acids

    • Catabolism of fatty acids produces acetyl-CoA and reducing power (NADH+H+, FADH2) in the mitochondria.
    • Anabolism of fatty acids requires acetyl-CoA and malonyl-CoA, as well as reducing power from NADPH+H+, and occurs in the cytosol in animals and chloroplasts in plants.

    Fatty Acid Biosynthesis - Place of Action

    • Fatty acid synthesis takes place in the cytosol of every cell with mitochondria, although the rate differs between cells.

    Fatty Acid Synthesis and NADPH+H+ Levels

    • Fatty acid synthesis occurs in cell compartments where NADPH+H+ levels are high, such as in the cytosol of animals and yeast.
    • Sources of NADPH+H+ include the pentose phosphate pathway and malic enzyme in adipocytes, and the pentose phosphate pathway in hepatocytes and mammary gland.

    The Triacylglycerol Cycle

    • 75% of free fatty acids (FFAs) released by lipolysis are reesterified to form TAGs, rather than being used for fuel under all metabolic conditions.
    • Some recycling occurs in adipose tissue, where FFAs from adipose cells are transported to the liver, remade into TAG, and redeposited in adipose cells.

    Glyceroneogenesis

    • Glyceroneogenesis makes DHAP for glycerol 3-phosphate generation during the TAG cycle.
    • It is an abbreviated version of gluconeogenesis in the liver and adipose tissue, converting pyruvate to DHAP.
    • It uses pyruvate, alanine, glutamine, or any substances from the Citric acid cycle as precursors for glycerol 3-phosphate.

    Fatty Acid Biosynthesis

    • Animals and plants store fat for fuel, with a typical 70-kg human having ~15 kg fat, enough to last 12 weeks.
    • Both TAGs and phospholipids contain a glycerol backbone and 2 or 3 fatty acids, respectively.

    Synthesis of Tag and Phospholipids

    • Most glycerol 3-phosphate comes from siphoning off DHAP from glycolysis via glycerol 3-phosphate dehydrogenase.
    • Some glycerol 3-phosphate is made from glycerol via glycerol kinase, a minor pathway in the liver and kidney, but absent in adipocytes.

    Synthesis of Phosphatidic Acid

    • Phosphatidic acid is the precursor for TAGs and phospholipids, with fatty acids attached by acyl transferases after activation by acyl-CoA synthetase.
    • Phosphatidic acid can be made into triacylglycerol or phospholipid.

    Phosphatidic Acid Modifications

    • Phosphatidic acid phosphatase (lipin) removes the 3-phosphate from phosphatidic acid, yielding 1,2-diacylglycerol.
    • The third carbon is then acylated with a third fatty acid, yielding triacylglycerol.

    Regulation of Triacylglycerol Synthesis

    • Insulin stimulates triacylglycerol synthesis.
    • Lack of insulin results in increased lipolysis, fatty acid oxidation, and sometimes ketone production.
    • Failure to synthesize fatty acids from carbohydrates and proteins leads to increased rates of fat oxidation and weight loss in untreated diabetes.

    The Triacylglycerol Cycle

    • 75% of free fatty acids (FFAs) released by lipolysis are reesterified to form TAGs, rather than being used for fuel under all metabolic conditions.
    • Some recycling occurs in adipose tissue, where FFAs from adipose cells are transported to the liver, remade into TAG, and redeposited in adipose cells.

    Glyceroneogenesis

    • Glyceroneogenesis makes DHAP for glycerol 3-phosphate generation during the TAG cycle.
    • It is an abbreviated version of gluconeogenesis in the liver and adipose tissue, converting pyruvate to DHAP.
    • It uses pyruvate, alanine, glutamine, or any substances from the Citric acid cycle as precursors for glycerol 3-phosphate.

    Fatty Acid Biosynthesis

    • Animals and plants store fat for fuel, with a typical 70-kg human having ~15 kg fat, enough to last 12 weeks.
    • Both TAGs and phospholipids contain a glycerol backbone and 2 or 3 fatty acids, respectively.

    Synthesis of Tag and Phospholipids

    • Most glycerol 3-phosphate comes from siphoning off DHAP from glycolysis via glycerol 3-phosphate dehydrogenase.
    • Some glycerol 3-phosphate is made from glycerol via glycerol kinase, a minor pathway in the liver and kidney, but absent in adipocytes.

    Synthesis of Phosphatidic Acid

    • Phosphatidic acid is the precursor for TAGs and phospholipids, with fatty acids attached by acyl transferases after activation by acyl-CoA synthetase.
    • Phosphatidic acid can be made into triacylglycerol or phospholipid.

    Phosphatidic Acid Modifications

    • Phosphatidic acid phosphatase (lipin) removes the 3-phosphate from phosphatidic acid, yielding 1,2-diacylglycerol.
    • The third carbon is then acylated with a third fatty acid, yielding triacylglycerol.

    Regulation of Triacylglycerol Synthesis

    • Insulin stimulates triacylglycerol synthesis.
    • Lack of insulin results in increased lipolysis, fatty acid oxidation, and sometimes ketone production.
    • Failure to synthesize fatty acids from carbohydrates and proteins leads to increased rates of fat oxidation and weight loss in untreated diabetes.

    Acetyl-CoA Transport and Fatty Acid Synthesis

    • In non-photosynthetic eukaryotes, acetyl-CoA is made in the mitochondria and transported into the cytosol for fatty acid synthesis at a cost of 2 ATPs.
    • The total cost of fatty acid synthesis is 3 ATPs per 2C unit, which is approximately 50% of the NADPH+H+ units necessary for fatty acid biosynthesis.

    Overview of Fatty Acid Synthesis

    • Fatty acids are synthesized in several passes, with each pass involving the reduction of a carbonyl carbon to a methylene carbon.
    • The acetate unit for fatty acid synthesis comes from activated malonate in the form of malonyl-CoA.

    The Acetyl-CoA Carboxylase Reaction

    • The acetyl-CoA carboxylase reaction is the committed step in fatty acid synthesis.

    Fatty Acid Synthase (FAS)

    • FAS I is a single polypeptide chain with 7 active sites in vertebrates, leading to a single product: palmitate (16:0).
    • FAS II is a separate enzyme system in plants and bacteria, producing a variety of fatty acid products (saturated, unsaturated, branched, etc.).

    Synthesis of Fat (Triacylglycerides) and Phospholipids

    • Animals and plants store fat (triacylglycerides) for fuel.
    • The typical 70-kg human has approximately 15 kg of fat, which can last for 12 weeks.
    • Animals, plants, and bacteria make phospholipids for cell membranes.
    • Both molecules contain a glycerol backbone and 2 (phospholipids) or 3 (triacylglycerides) fatty acids.

    Synthesis of Backbone of TAGs and Phospholipids

    • Most glycerol 3-phosphate comes from dihydroxyacetone phosphate (DHAP) via glycerol 3-phosphate dehydrogenase.
    • Some glycerol 3-phosphate is made from glycerol via glycerol kinase (minor pathway in liver and kidney, absent in adipocytes).

    Catabolism and Anabolism of Fatty Acids

    • Catabolism of fatty acids produces acetyl-CoA and reducing power (NADH+H+, FADH2) in the mitochondria.
    • Anabolism of fatty acids requires acetyl-CoA and malonyl-CoA, as well as reducing power from NADPH+H+, and occurs in the cytosol in animals and chloroplasts in plants.

    Fatty Acid Biosynthesis - Place of Action

    • Fatty acid synthesis takes place in the cytosol of every cell with mitochondria, although the rate differs between cells.

    Fatty Acid Synthesis and NADPH+H+ Levels

    • Fatty acid synthesis occurs in cell compartments where NADPH+H+ levels are high, such as in the cytosol of animals and yeast.
    • Sources of NADPH+H+ include the pentose phosphate pathway and malic enzyme in adipocytes, and the pentose phosphate pathway in hepatocytes and mammary gland.

    Fatty Acid Synthesis

    • The overall goal is to attach an acetate unit (2C) from malonyl-CoA to a growing chain and then reduce it
    • The reaction involves cycles of four enzyme-catalyzed steps:
      • Condensation of the growing chain with activated acetate
      • Reduction of carbonyl to hydroxyl
      • Dehydration of alcohol to trans-alkene
      • Reduction of alkene to alkane
    • The growing chain is initially attached to the enzyme via a thioester linkage

    Acyl Carrier Protein (ACP)

    • ACP serves as a shuttle in fatty acid synthesis
    • Contains a covalently attached prosthetic group, 4'-phosphopantetheine
    • Has a flexible arm to tether the acyl chain while carrying intermediates from one enzyme subunit to the next
    • Delivers acetate (in the first step) or malonate (in all the next steps) to the fatty acid synthase

    Charging

    • Involves the addition of Acetyl-CoA to ACP and further transfer to –SH of KS in synthesis denovo
    • Also involves the addition of Malonyl-CoA to ACP
    • By using activated malonyl groups in the synthesis of fatty acids and activated acetate in their degradation, the cell makes both processes energetically favorable, although one is effectively the reversal of the other

    Enzymatic Activities

    • β-ketoacyl-ACP synthase (KS): coupling condensation to decarboxylation of malonyl-CoA makes the reaction energetically favorable
    • β-ketoacyl-ACP reductase (KR): reduces β-ketoacyl-ACP to form D-β-hydroxyacyl-ACP
    • β-hydroxyacyl-ACP dehydratase (DH): dehydrates D-β-hydroxyacyl-ACP to form trans-Δ2-enoyl-ACP
    • Enoyl-ACP reductase (ER): reduces trans-Δ2-enoyl-ACP to form acyl-ACP

    Synthesis of Phosphatidic Acid and Triacylglycerol

    • Phosphatidic acid is the precursor for TAGs and phospholipids
    • Fatty acids are attached by acyl transferases, after activation by acyl-CoA synthetase
    • Phosphatidic acid can be modified to form phospholipids or TAGs
    • Phosphatidic acid phosphatase (lipin) removes the 3-phosphate from phosphatidic acid to yield 1,2-diacylglycerol

    Regulation of Triacylglycerol Synthesis by Insulin

    • Insulin stimulates triacylglycerol synthesis
    • Lack of insulin results in increased lipolysis, increased fatty acid oxidation, and failure to synthesize fatty acids from carbohydrates and proteins

    Triacylglycerol Cycle

    • 75% of free fatty acids released by lipolysis are reesterified to form TAGs
    • Some recycling occurs in adipose tissue, and some FFAs are transported to the liver, remade into TAG, and redeposited in adipose cells

    Glyceroneogenesis

    • Generates DHAP for glycerol 3-phosphate generation during TAG cycle
    • Occurs during lipolysis, when glycolysis in adipocytes is inhibited
    • Converts pyruvate to DHAP using pyruvate, alanine, glutamine, or any substances from the Citric acid cycle as precursors for glycerol 3-phosphate

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    Medical Biochemistry Lecture Notes PDF

    Description

    Learn how acetyl-CoA is transported from the mitochondria to the cytosol for fatty acid synthesis in non-photosynthetic eukaryotes, including the energy cost and NADPH requirements.

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