Exam #2 TAG synthesis

  1. What happens to newly synthesized TAG in liver and adipose tissue?
    • In liver, it is packed in VLDL to delivery endogenously derived lipids around body.
    • In adipose tissue, it is stored. 
  2. Who has priority: phospholipids or TAG synthesis?
  3. Describe mechanism of TAG hydrolysis starting with epinephrine/glucagon and ending with fates of FAs and glycerol. 5
    • 1. Ep/glucagon bind to 7-transmembrane G-protein coupled receptor. G protein activates adenylate cyclase: ATP--> cAMP. cAMP activates PKA.
    • 2. PKA phosphorylates and activates Hormone Sensitive Lipase which activates ATGL (adipocyte TG lipase) to cleave off FAs (1st and/or 3rd) leaving MAG.
    • 3. MAG lipase hydrolyzes MAG to free glycerol and 3 FAs. 
    • 4. Glycerol --> liver for GNG
    • 5. FAs --> acetyl CoA for TCA cycle for energy.
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  4. Describe mechanism of TAG synthesis after fasting starting with insulin and ending with fatty acid uptake.
    • 1. Insulin binds to receptor activating phosphatase that d'plates and deactivates HSL. Decreases lipolysis
    • 2. Also activates phosphodiesterase that breaks down cAMP stopping cAMP secondary pathway. Decreases lipolysis
    • 3. Increases glucose entry (GLUT 4) for glycerol backbone
    • 4. Increases FA entry from lipoproteins by increasing lipoprotein lipase activity. Insulin activates ApoCII which activates LPL to cleave off FAs for uptake into body. 
  5. Where is lipoprotein lipase synthesized and secreted from? What is its main function? What is it directly activated by? What hormone activates it as well?
    • LPL is synthesized and secreted by fat, heart, and skeletal muscle.
    • It's main function is to increase FA entry into cells via lipolysis from TAGs
    • Activated by ApoCII which is activated by insulin
  6. What specifically happens to released FAs? 4 steps
    • 1. Diffuse through cell membrane and travel with albumin through blood.
    • 2. Transported to tissues, enter cells
    • 3. Activation by acyl CoA synthetase
    • 4. Oxidized for energy in mitochondria OR re-esterified (over 50% of FAs are re-esterified). 
  7. What specifically happens to released glycerol from TAG hydrolysis?What are the 3 possible products?
    • 1. Glycerol cannot return to adipocytes (no glycerl kinase) so goes to liver for phosphorylation/activation.
    • 2. Can form TAG 
    • 3. Or can form DHAP for glycolysis or GNG. 

    TAG, glucose, or undergo DHAP for TCA cycle
  8. What would happen if you had an ATGL deficiency?
    Since ATGL (acyl TAG lipase) is essential for TAG hydrolysis, you wouldn't be able to properly lipolize your TAGs into glycerl and FAs leading to accumulation of TAGs in bad places (i.e. heart)

    Knockout mouse. 
  9. Does HSL move at all?
    Yes, once it's phosphorylated it moves from the cytosol to the surfaces of the lipid droplets!
  10. What happesn in basal lipolysis vs. stimulated lipolysis?
    In basal lipolysis, ATGL is located partially to the LD and HSL in cytoplasm. Rate of lipolysis is VERY low --> released FAs are resynthesized back into lipid (futile cycling) or directed toward oxidation in mitochondria. 
  11. What are lipid droplets surrounded by? What enzymes deal with dietary TAG hydrolysis? 2

    Pancreatic lipase and colipase in gut lumen
  12. Why can't glycerol go back into fat cell and be reused? Why does a fat cell need to take up glucose from blood?
    Adipose tissue does not have glycerol kinase, so cannot process free glycerol.

    Because needs substrate for backbone of TAG (glycerol) which is a product of glycolysis and cannot use free glycerol.
  13. What would happen physiologically if a person had no fat cells on his body? Will he be healthy? What is this called? What ist his like? Will he be full all the time? Where will extra energy be stored?

    It's called lipodystrophy. No, because adipose tissue secretes hormones such as estrogen, adiponectin and leptin. Adiponectin is important (higher levels) for protecting against metabolic derangements. Leptin = satiety factor. Person will be constantly hungry and with no adipocytes, extra energy will be stored in bad places ilke the heart!

    Like ATGL deficiency.

    Inject leptin (peptide hormone)
  14. What are the steps for FA oxidation? 5

    What is the final product? 3
    • 1. Acyl CoA synthetase: FA + ATP + CoA --> FA CoA
    • 2. Carnitine palmitoyl transferase 1 (CPT1) combines fatty acyl CoA and carnitine to form acylcarnitine + CoA (plucks off CoA).
    • 3. Acylcarnitine enters mtitochondria via carnitine-FA transporter. 

    • 4. CPT2: Acyl carnitine --> FaCoA (carnitine is released, recycled and exits via carnitine-FA transporter).
    • 5. FaCoA undergoes B-oxidation. Final product: acetyl CoA, NADH, FADH2
  15. Where does B-oxidation take place specifically? What is the transporter for FA called? 
    Mit matrix

    Carnitine-FA transporter
  16. How is B-oxidation regulated? 5

    Which is regulated step?
    • 1. Malonyl CoA (from ACC - FA synthesis) inhibits CPT1 (Low insulin:glucagon inhibits ACC, inhibiting malonyl CoA production, so CPT1 is free). 
    • 2. Magnitude of lipolysis (based on low insulin:glucagon/ep/ACTH) how many FAs have been released
    • 3. CPT-1 and entry of acyl CoA into mitochondria (this entire transport system is the major regulated step!)
    • 4. AMPK - signals low energy, inhibits anabolic pathways, inhibits ACC --> less maCoA and more CPT1.
    • 5. PPARalpha - nuclear transcription factor whose synthesis is increased by cortisol (during fast). Works like steroid hormone, interacts w/ CPT1 gene promoter and enhances gene expression of B-oxidation enzymes including CPT1. 
  17. What does AMPK downregulate? 3
    Syn of FAs, TAGs, and cholesterol
  18. Where is carnitine synthesized? From what 2 AAs?  Where else can you get carnitine? How common is carnitine deficiency?
    Synthesized in liver and kidney from lysine and methionine. From diet. 

    Not common - if there is a deficiency, generally genetic. 
  19. What are the 4 main functions of B-oxidation?
    • 1. Supplies GNG with ATP and NADH (directs pyruvate/lactate away from oxidation towards glucose synthesis by inhibiting PDH!)
    • 2. Provides ketone bodies for peripheral tissues
    • 3. Spares protein degradation during fasting/starvation
    • 4. Spares glucose use in peripheral tissues
  20. What happens if B-oxidation is blocked?
    GNG would most likely be impaired leading to hypoglycemia. 
  21. Describe pathway for ketone body synthesis 4 steps - 4th step is split. 3 enzymes total. Which is RDS?

    • 1. Fatty acid splits into acetyl CoA (TCA) and acetoacetyl CoA (substrate for ketone body syn).
    • 2. HMG CoA synthase: acetoacetylCoA --> HMG CoA
    • 3. HMG CoA lyase: splits HMG CoA back into acetyl COA and acetoacetate (basically to get rid of CoA). 
    • 4. Acetoacetate can spontaneously convert to acetone or turn into B-hydroxybutyrate (Carboxylic acid) via b-hydroxybutyrate dehydrogenase. 

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  22. How many ATP needed to fund B-oxidation? How many ATPs are generally returned?
    • (C-2)/2 NADH and FADH2 (5 ATP total). 
    • 12 ATP for each acetyl CoA (C/2*12)

    -2 ATP needed for activation of palmitate to palmitoyl CoA>
  23. Under what two physiological conditions does ketogenesis occur? By what organ? What are the 3 ketone bodies?
    • 1. Starvation or low CHO diet.
    • 2. Liver
    • 3. Acetone, acetoacetate, B-hydroxybutyrate
  24. What are the 3 main functions of ketogenesis?
    • 1. PRovide energy fuel from TAG to brain/peripheral tissues
    • 2. Reduce/conserve glucose use
    • 3. Prevent excess loss of skeletal protein for GNG

    many are like FA functions. 
  25. What happens biochemically to begin ketogenesis in liver?
    • 1. Liver is flooded with FAs mobilized from adipocytes
    • 2. Resulting elevated hepatic acetyl CoA inhibits PDH and activates pyruvate carboxylase (GNG) instead of TCA
    • 3. Since OAA is used by liver for GNG, acetyl CoA is channeled into ketogenesis. 

    Rise is NADH shifts OAA to malate, pushing acetyl CoA away from GNG and into ketogenesis. 
  26. How is ketone body formation regulated? 5
    • First 2 are same as FA oxidation
    • 1. Magnitude of lipolysis (amount of FA released)
    • 2. CPT1 and entry of acetyl CoA into mitochondria 
    • 3. Entry of acetyl CoA into TCA cycle (lack of entry increases amount for ketone synthesis)
    • 4. Increased glucagon increases syn of HMG CoA synthase
    • 5. Lack of insulin. 
  27. What happens after liver makes ketone bodies? Why are ketone bodies exported and not used in liver? Where does the CoA come from? What if B-hydroxybutyrate enters first?

    Pathway starting from acetoacetate?
    Liver lacks succinyl CoA acetoacetate CoA transferase (SCAACT) and can't activate acetoacetate to active CoA form.

    So, acetoacetate and B-hydroxybutyrate are exported to peripheral tissue that DO have this enzyme. 

    CoA comes from succinyl CoA

    Then it must be converted to acetoacetate first.

    Acetoacetate --> acetoacetate CoA --> acetyl CoA enters TCA cycle. 
  28. What tissues can never use fatty acids or ketone bodies?
    RBCs bc no mitochondria
  29. If a person can't make ketones, what will happen to serum glucose during a prolonged fast? 
    Hypoglycemia. Ketone bodies help save plasma glucose by offering themselves to peripheral tissues to create energy instead. 
  30. Is B-hydroxybutyrate a ketone? 
    No, it's a carboxylic acid. 
  31. How does eating unripe ackee ackee fruit inhibit FA oxidation?
    It has a compound that binds irreversibly to carnitine, CPT 1 and 2, as well as CoA reducing bioavailability for actaul energy production. W/o energy for GNG, glucose stores are depleted --> hypoglcyemia.
Card Set
Exam #2 TAG synthesis
tag synthesis, boxidation