Metabolic: lecture 27
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Questions and Answers

What is the effect of malonyl-CoA on fatty acid entry into mitochondria?

  • Stimulates fatty acid entry
  • Has no effect on fatty acid entry
  • Inhibits fatty acid entry (correct)
  • Promotes fatty acid oxidation

    • Which enzyme is activated by protein phosphatase in the presence of high blood glucose?

  • Hormone-sensitive lipase
  • Acetyl-CoA carboxylase (correct)
  • Glycogen phosphorylase kinase
  • Glycogen synthase

    • How does a decrease in malonyl-CoA affect fatty acid oxidation?

  • Increases fatty acid oxidation (correct)
  • Has no impact on fatty acid oxidation
  • Inhibits fatty acid oxidation
  • Decreases fatty acid oxidation

    • What is the end product resulting from the acylation of the third carbon of diacylglycerol?

    <p>Triacylglycerol (C)</p> Signup and view all the answers

    What role does PKA play in response to low blood glucose levels?

    <p>Regulates multiple pathways including glycogen metabolism (C)</p> Signup and view all the answers

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

    <p>Condensation of acetyl-CoA and malonyl-CoA (B)</p> Signup and view all the answers

    Which compound is required for the transformation of 7 acetyl-CoAs into 7 malonyl-CoAs?

    <p>ATP (C)</p> Signup and view all the answers

    What byproduct is formed during the synthesis of palmitate from 7 malonyl-CoA and other reactants?

    <p>7 CO2 (A)</p> Signup and view all the answers

    Which enzyme is responsible for the final step of releasing palmitate during its synthesis?

    <p>Thioesterase (TE) (A)</p> Signup and view all the answers

    What is the primary product formed from elongating palmitate through the addition of 2 carbon units?

    <p>Stearate (18:0) (B)</p> Signup and view all the answers

    What is the role of malonyl-CoA in fatty acid synthesis?

    <p>It provides the acetate units for the growing fatty acid chain. (C)</p> Signup and view all the answers

    Which enzyme is responsible for the formation of malonyl-CoA?

    <p>Acetyl-CoA carboxylase. (B)</p> Signup and view all the answers

    How is acetyl-CoA carboxylase (ACC) regulated?

    <p>Inhibited by palmitoyl-CoA and activated by citrate. (A)</p> Signup and view all the answers

    What function does the acyl carrier protein (ACP) serve in fatty acid synthesis?

    <p>It delivers and shuttles intermediates between enzyme subunits. (C)</p> Signup and view all the answers

    What is a consequence of the phosphorylation of acetyl-CoA carboxylase (ACC)?

    <p>It diminishes the sensitivity to citrate stimulation. (D)</p> Signup and view all the answers

    What type of interaction occurs between the fatty acid synthase enzymes?

    <p>They function as a dimer containing multiple enzymes. (A)</p> Signup and view all the answers

    What occurs during the initial step of the fatty acid synthesis process?

    <p>The acetate unit is attached to the fatty acid chain. (C)</p> Signup and view all the answers

    What is the role of the prosthetic group 4’-phosphopantetheine in the ACP?

    <p>It tethers acyl chains while shuttling intermediates. (B)</p> Signup and view all the answers

    Flashcards

    Fatty Acid Synthesis

    The process of building fatty acids, one acetate unit at a time, starting with activated malonate (malonyl-CoA).

    Malonyl-CoA formation

    The first step in fatty acid synthesis, where activated malonate (malonyl-CoA) is created from acetyl-CoA and bicarbonate (HCO3-).

    Acetyl-CoA carboxylase (ACC)

    Enzyme responsible for the conversion of acetyl-CoA to malonyl-CoA—the rate-limiting step in fatty acid synthesis.

    Acyl Carrier Protein (ACP)

    A protein that shuttles the growing fatty acid chain between the different enzymatic active sites of fatty acid synthase.

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    Fatty Acid Synthase (FAS)

    A multi-enzyme complex that catalyzes the repeated addition of two-carbon units to a growing fatty acid chain.

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    Regulation of ACC

    Acetyl-CoA carboxylase (ACC) is regulated by factors like palmitoyl-CoA (feedback inhibition) and citrate (activation).

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    Citrate's role in fatty acid synthesis

    High levels of citrate signal excess energy to be converted into fat, activating ACC.

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    Fatty acid synthase dimer

    Fatty Acid Synthase is a dimeric structure, each monomer containing several catalytic subunits and Acyl Carrier Protein.

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    Fatty Acid Synthesis Steps

    The process of building fatty acids from acetyl-CoA and malonyl-CoA, involving a repeating cycle of condensation, reduction, dehydration, and reduction.

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    Palmitate Synthesis Stoichiometry

    Seven acetyl-CoAs and seven malonyl-CoAs, along with 14 NADPH, create one palmitate molecule (16 carbons) through a series of reaction steps, releasing 7 CO2, 8 CoA, and 6 H2O molecules.

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    Elongation of Fatty Acids

    The process of adding carbon atoms to a fatty acid chain, often taking place in the endoplasmic reticulum or mitochondria, extending the fatty acid's length.

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    Fatty Acid Desaturation

    The introduction of double bonds into a fatty acid chain, typically conducted by a fatty acyl-CoA desaturase.

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    -ketoacyl-ACP synthase (KS)

    Enzyme that catalyzes the condensation reaction between an acetyl group (or other acyl group) and a malonyl group in fatty acid synthesis.

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    Fatty Acid Metabolism Regulation

    Fatty acid metabolism is tightly controlled by hormones like insulin and glucagon, and their effects on enzymes like Acetyl-CoA carboxylase (ACC) and hormone-sensitive lipase.

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    Malonyl-CoA's Role

    Malonyl-CoA inhibits carnitine acyltransferase 1 (CAT1), preventing fatty acid transport into mitochondria for oxidation when fuel source is carbohydrates.

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    Glucagon's Effect on ACC

    Low blood sugar (glucagon release) activates protein kinase A (PKA) and AMP-activated protein kinase (AMPK), inhibiting Acetyl-CoA carboxylase (ACC) and promoting fatty acid oxidation.

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    Triacylglycerol (TAG) Synthesis

    TAGs are synthesized from glycerol-3-phosphate (G3P), with fatty acids attached to the glycerol backbone by acyltransferases.

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    Phosphatidic Acid's Role in Lipid Synthesis

    Phosphatidic acid, a precursor to both TAGs and phospholipids, is modified to form lipids by lipin or by adding a polar head group.

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    Study Notes

    Fatty Acid Synthesis

    • Fatty acids are built in multiple steps, adding one acetate unit at a time. Synthesis is of 2 carbons at a time.
    • Acetate units are derived from activated malonate, in the form of malonyl-CoA. This is the active form.
    • The overall mechanism includes attaching a two-carbon unit (derived from malonyl-CoA) to a growing fatty acid chain, via an Acyl Carrier Protein (ACP). Then, reduction occurs.
    • Acetyl CoA is converted to malonyl CoA for fatty acid chain elongation.

    Stage 1: Malonyl-CoA Formation

    • Acetyl-CoA carboxylase (ACC) is the enzyme that catalyzes the formation of malonyl-CoA from acetyl-CoA and HCO3⁻.
    • ACC is a multi-subunit enzyme.
    • It has three subunits, each containing a biotin molecule.
    • Biotin is a cofactor that plays a crucial role in carboxylation reactions.
    • The enzyme uses ATP and bicarbonate to form malonyl-CoA.

    Stage 2: Fatty Acid Synthase (FAS)

    • Acyl Carrier Protein (ACP) acts as a shuttle.
    • ACP carries the substrate and product without leaving the protein.
    • ACP has a prosthetic group (4'-phosphopantetheine).
    • This group acts as a flexible arm that tethers the acyl chain.
    • FAS delivers acetate in the first step, or malonate in the subsequent steps to the fatty acid synthase.
    • It shuttles between active sites, during four-step reactions.
    • Fatty acids are synthesized in units of 2 carbons at a time.

    Fatty Acid Synthesis Regulation

    • Acetyl-CoA carboxylase (ACC) is regulated by both feedback inhibition and allosteric activation.
    • It is inactivated by palmitoyl-CoA.
    • It is activated by citrate.
    • Citrate from mitochondria enters the cytosol and activates ACC; citrate signals excess energy to convert to fat.
    • ACC is a key enzyme in fatty acid synthesis.

    Fatty Acid Cycle

    • Fatty acids are synthesized by a repeating four-step reaction sequence.

    • The stages involve: condensation, reduction from carbonyl to hydroxyl, dehydration to trans alkene, and reduction from alkene to alkane.

    Overall Palmitate Synthesis

    • 8 repeat to synthesize 16-carbon palmitate.
    • Each cycle adds 2 carbons.

    Palmitate Elongation

    • Elongation systems (part of the endoplasmic reticulum and mitochondria) can be used to create longer fatty acids.
    • Each elongation step adds 2 carbons.
    • Stearate (18:0) is the most common product of elongation.

    Fatty Acid Desaturation

    • Double bonds are introduced to fatty acids through an enzyme-catalyzed reaction known as desaturation.
    • Through desaturation reactions in the endoplasmic reticulum, unsaturated fatty acids are produced.
    • Fatty acyl-CoA desaturase (a mixed function oxidase) is the enzyme responsible.
    • NADPH provides the electrons required for the reaction.
    • Oxygen acts as the final electron acceptor for the reaction.

    Fatty Acid Metabolism Regulation

    • High blood glucose: insulin activates ACC, which converts acetyl-CoA to malonyl-CoA; this inhibits fatty acid oxidation; FA synthesis increases.
    • Low blood glucose: glucagon release leads to PKA and AMPK activation; this inactivates ACC, which reduces malonyl-CoA levels allowing fatty acid oxidation to proceed.

    Synthesis of storage lipids

    • Triglycerides are synthesized from glycerol-3-phosphate and fatty acids.
    • Cholesterol is another type of storage lipid.

    Synthesis of Phospholipids

    • Phosphatidic acid is the precursor to phospholipids and triglycerides.
    • Phosphatidic acid phosphatase removes the phosphate group, producing 1,2-diacylglycerol.
    • The 3rd carbon of 1,2-diacylglycerol can then be acylated, yielding the triacylglycerol.

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    Lecture 27 FAS PDF

    Description

    This quiz covers the essential steps of fatty acid synthesis, emphasizing the role of malonyl-CoA and the enzymatic processes involved. Learn about the key enzymes, including Acetyl-CoA carboxylase and Fatty Acid Synthase, as well as the importance of Acyl Carrier Protein in this biochemical pathway.

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