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Fuel Metabolism-Learning Objectives > L18: Fatty Acid Synthesis > Flashcards

L18: Fatty Acid Synthesis Flashcards

1
Q

LO1: Describe the effects of insulin on fatty acid synthesis and storage, specifying tissues and pathways that are involved

A
  • Insulin stimulates FA synthesis by activating protein phosphatase that dephosphorylates acetyl-CoA carboxylase (rate limiting step in FA synthesis)
  • Insulin also stimulates synthesis of triglycerides from FA synthesis by promoting uptake of FA/glucose in adipose tissue
  • Insulin also stimulates storage of triglycerides by keeping hepatic lipase inactive (dephosphorylated) so triglycerides stay in storage
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2
Q

LO2: Describe the citrate shuttle and its role in fatty acid synthesis

A
  • acetyl-CoA is not permeable to the IMM, so it must be transported out of the mitochondrial matrix to the cytosol via the citrate shuttle
  • citrate lyase converts citrate to acetyl-CoA and OAA in cytosol (OAA can be recycled to malate, then pyruvate)

citrate+ATP+CoAsh—>Acetyl-CoA+OAA+ADP +Pi

-acetyl-CoA=precursor to malonyl CoA, converted by acetyl CoA carboxylase (requires biotin+ATP) in the rate limiting step of FA synthesis

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3
Q

LO3: Name the enzyme that catalyzes the rate limiting step in fatty acid synthesis, describe the reaction it catalyzes, and describe three different mechanisms for regulation of this enzyme

A

RATE LIMITING STEP IN FA SYNTHESIS
-acetyl CoA carboxylase (requires biotin+ATP) converts acetyl-CoA to malonyl CoA

REGULATION

  • allosteric: activation by citrate, inhibition by palmitoyl-CoA
  • covalent: inhibited by phosphorylation (glucagon), activated by dephosphorylation (insulin)
  • synthesis: stimulated by high-carb diet (mediated by insulin) or fat-free diet; inhibited by high fat diet or fasting (mediated by glucagon
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4
Q

LO4: Name the substrates required for FA synthesis, how much of each is required for palmitoyl CoA synthesis, and the reactions by which the substrates are generated

A
  • acetyl-CoA transported via citrate shuttle (originally from pyruvate) (1)
  • NADPH from transhydrogenase sequence in citrate shuttle (OAA to pyruvate) and the PPP (14)
  • malonyl-CoA generated from carboxylation of acetyl-CoA by acetyl-CoA carboxylase (7)
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5
Q

LO5: Describe the role of citrate synthase, citrate lyase, malate dehydrogenase, malic enzyme, and the PPP in FA synthesis

A

CITRATE SYNTHASE-catalyzes condensation of acetyl-CoA+OAA to form citrate, which is transported out of the mitochondria and into the cytosol to regenerate acetyl-CoA

CITRATE LYASE-catalyzes conversion of citrate to acetyl-CoA in cytosol so acetyl-CoA can be used to make malonyl CoA for FA synthesis

MALATE DEHYDROGENASE- converts OAA to malate in cytosol so OAA can be regenerated (via pyruvate) to re-enter citrate cycle; also provides NADPH

MALIC ENZYME-converts malate to pyruvate so OAA can be regenerated (via pyruvate) to re-enter citrate cycle; also provides NADPH

PPP-provides reducing compounds needed for FA synthesis

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6
Q

LO6: Describe the reaction catalyzed by the FAS enzyme, naming the four core reactions catalyzed by FAS

A

-FAS enzyme catalyzes formation of palmitic acid

  1. Priming of acetyl group by acetyl-CoA transacetylase
  2. Priming of malonyl group by malonyl-CoA transacetylase
  3. CORE REACTIONS OF FA SYNTHESIS
    a. condensation with malonyl-ACP by condensing enzyme; CO2 and energy released
    b. reduction of B-ketoacyl-ACP to B-hydroxyacyl-ACP by B-ketoacylreductase (requires NADPH)
    c. Dehydration of B-hydroxyacyl-ACP by B-hydroxyacyldehydratase
    d. reduction of double bond in enoyl-ACP gives a fully saturated FA that has been extended by two carbons; requires NADPH and enoyl-ACP reductase
  4. Acyl group transferred to condensing enzyme and released ACP primed with new malonyl group to repeat cycle
  5. FA (16:) released from FAS complex and transferred to CoASH or H2O by either palmitoyl-ACP, CoA transferase, or Deacylase
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7
Q

LO7: Describe the role of acyl carrier protein (ACP) in FA synthesis, and name the cofactor for ACP

A

ACP is part of the FAS

  • anchors the growing FA chain
  • cofactor=phosphopantetheine (covalently attached)
  • at end of cycle, ACP is primted with new malonyl group to repeat the cycle
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8
Q

LO8: Compare/contrast the end products of FA synthesis in liver and lactating mammary gland, and discuss the physiological significance of the differences

A
  • liver produces 16:0 FA chain (palmitic acid) that can be used as a building block for other things
  • mammary gland produces 10:0 FA chain (decanoic acid) that is of medium chain length, so it can go directly into the intestinal lumen and blood without processing (good for infants whose digestive system is underdeveloped)
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9
Q

LO9: Describe the mechanism by which fatty acids that are synthesized in the liver are delivered to adipose tissue for storage

A

An extracellular enzyme, lipoprotein lipase, releases FAs from lipoprotein triglycerides (chylomicrons or VLDLs), which are then taken up by fat cells (adipocytes) in the interstitial space and converted to triglyceride

  • stimulated by insulin and ApoCII
  • LPL works by signalling LDLs/their APOCII
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10
Q

LO10: Describe the reactions required to convert FAs to triglyceride in adipose tissue

A
  1. After uptake of FA, they’re converted to fatty acyl-CoA by transferring them to C-1 and C-2 of glycerol-3-P (from glycolysis) to make phosphatidic acid
  2. Phosphate group is removed, creating diglyceride
  3. Another FA is transferred from fatty acyl-CoA to 3-OH of diglyceride to create a triglyceride
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11
Q

LO11: Describe the role of glucose in triglyceride synthesis in adipose tissue

A

Glucose provides glycerol-3-P during glycolysis that can be used in conversion of FAs to fatty acyl-CoA for triglyceride synthesis

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12
Q

LO12: Describe the general structure of the major phospholipids. Name 5 major phospholipid classes.

A

-glycerol backbone with three acids esterified to the hydroxyl groups; two are long chain fatty acids (C1 and C2) and third is phosphoric acid (C3)

Phosphatidic acid (no side group)
phosphatidylserine (+serine)
phosphatidylethanolamine (+ethanoloamine)
phosphatidylcholine (+choline)
phosphatidylinositol (+inositol)
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13
Q

LO13: List five functions of phospholipids

A
  1. major component of lipid bilayer
  2. enzyme activation
  3. second messenger signaling
  4. lung function (dipalmitoyl phosphatidylcholine is in lung surfactant)
  5. structural component of bile and mixed micelles (lipid digestion)
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14
Q

LO14: Describe the mobilization of FAs from triglycerides from lipases (4 types)

A

-lipoprotein lipase releases FAs from lipoprotein triglycerides

TRIACYLGLYCEROL LIPASES-work together to hydrolyze FAs from triglyceride stores

  • adipose triacylglycerol lipase (ATGL) found on the surface of lipid droplets; triacylglycerol is its primary substrate
  • hormone sensitive lipase (HSL) long form found in steroid producing organs (gonads, adrenal glands) while short form is found in adipose tissue; diacylglycerol is its primary target and it is stimulated by glucagon, epinephrine, ACTH/inhibited by cortisol and thyroid hormone
  • monacylglycerol lipase (MGL) found in adipocytes; monoacylglycerol is its primary target
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Fuel Metabolism-Learning Objectives (27 decks)

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