Lect 6 Lipid Synthesis Flashcards Preview

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Flashcards in Lect 6 Lipid Synthesis Deck (19):
1

3 Main Functions of Lipids

Fuel Store (Energy)

Structural Component (PM)

Signaling Molecules

2

Major Source of C for FA Synthesis?

Dietary CHO

3

What is the main FA Synthesis Location?

Where can it also take place?

Primarily Liver

Adipose, Brain, Kidney, Lactating Mammary Glands

4

What occurs in Phase I FA Synthesis

Cytosolic Entry of Acetyl CoA

What is ATP Citrate Lyase Regulated By?

  • Condensation of OAA + Acetyl CoA via Citrate Synthase    --> Citrate
    • Citrate Shuttle/Transporter to Cytosol
  • Citrate --> OAA + Acetyl CoA via ATP Citrate Lyase
  • OAA converted to Malate (Malate Dehydrogenase)
    • --> Mitochondria --> OAA
    • --> Pyruvate (Malic enzyme) --> Mitochondria --> OAA (PC)
  • Citrate Lyase regulated by Glucose & Insulin (+), and PUFA & Leptin (-)

5

What occurs in FA Synthesis Phase II - Synthesis of Malonyl CoA

What does the enzyme add/require?

What is the regulation of the enzyme?

  • Acetyl CoA (2C) --> Malonyl CoA (3C) via Acetyl CoA Carboxylase (ACC) - Adds CO2
    • Uses ATP and Biotin is co-enzyme
  • Rate Limiting Step in FA Biosynthesis!!!!!
  • Regulated by Citrate and Insulin (+) & Glucagon, Epi, High AMP, Palmitate, and PUFA (-)

6

Malonyl CoA is the substrate for what enzyme?

What does it regulate and why is it important?

  • Substrate for FA Synthase (FAS)
  • Inhibits Carnitine Acyltransferase 
    • Rate Limiting Step in FA degradation (prevents simultaneous synthesis & degradation)

7

What occurs in FA synthesis Phase III - FA Chain Formation

How is FA Synthase regulated?

  • 2C units from Malonyl CoA added to fatty acyl chain 
    • 7 reactions to form Palmitate (16:0)
  • Occur on Fatty Acid Synthase (FAS) Complex
  • Regulated by Insulin and Glucocorticoid Hormones (+) & PUFA (-)

8

Fatty Acid Synthase (FAS) is a large _ complex composed of _ arranged in a _ conformation. 

How many proteins in each dimer?

 

  • Multi Enzyme Complex
  • 2 Identical Dimers 
  • Arranged in Head to Tail conformation
    • Each has 7 enzyme activities and Acyl Carrier Protein (ACP)
      • ACP has flexible arm 

9

Describe the Palmitate Synthesis Reaction

How many rounds are completed?

1 Acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14H+ = CH3(CH2)14COO- + 14 NADP+ + 8 CoA + 6 H2O

7 Rounds

10

What are the Reactions Catalyzed by FAS

  • Condensation: Acetyl CoA (2C) + Malonyl CoA (3C) --> 4C and release CO
  • Reduction: NADPH --> NADP
  • Dehydration: H2O Removed
  • Reduction: NADPH --> NADP+
  • Repeat 6 more times (7 total) --> Palmitate (16C)

11

What are the Sources of NADPH During FA Synthesis

Malic Enzyme: 1

PPP: 2-12

12

Regulation of ATP Citrate Lyase (Phase I)

Activate: Phosphorylation, Glucose, Insulin

Inhibitors: Polyunsaturated FAs (PUFAs), Leptin

13

Regulation of Acetyl CoA Carboxylase (ACC) (Phase II)

Allosteric Inhibitors?

What causes phosphorylation?

What causes dephosphorylation?

  • Allosteric Regulation: 
    • Activate: Citrate
    • Inhibit:  Long Chain FAs (Palmitate)
  • Phosphorylation (Inhibit)
    • Epi (via PKA activation)
    • Glucagon (via PKA activation)
    • AMP (via AMPK activation)
  • Dephosphorylation (Activate)
    • Insulin (via protein phosphatase activation)

14

Regulation of Fatty Acid Synthase (FAS) (Phase III)

What increases and decreases activity?

  • Increases:
    • Insulin & Glucocorticoid hormones increase synthesis
    • High CHO/Low fat diet increases synthesis
  • Decreases
    • High fat diets/Starvation lowers synthesis
    • High PUFA suppresses synthesis

15

Leptin: Fat-Brain Axis

Where does it come from?

How does it work and where does it go?

  • Adipose Tissue in direct proportion to fat mass
  • Act through Leptin Receptor (Hypothalamus)
  • Regulate BW
    • Inhibit food intake
    • Stimulate energy expenditure

16

Longer Chain FA Synthesis - Elongation

Where does this occur? Distinctions?

  • Palmitate --> Longer Chain FA in SER or Mitochondria
    • ​SER: Malonyl CoA as donor
    • Mitochondria: Acetyl CoA as donor
  • NADPH reducing power

17

Desaturation means what?

What catalyzes this reaction?

Which locations can humans introduce double bonds?

  • Introduce double bonds in FA
  • Occur in SER via Acyl CoA Desaturases using NADH/NADPH
  • Humans have 4 desaturases (4-5, 5-6, 6-7, and 9-10)
  • FA w/ double bond beyond C9-10 cannot be synthesized
    • Ex: omega-3 and omega-6 (Essential FAs)

18

Desaturase Regulation

Where in FA does cholesterol induce desaturase?

  • Activated: Insulin
  • Inhibited: dietary PUFAs
  • Dietary cholesterol induces C9-10 desaturase, inhibits all others

19

Essential FAs  include what type?

What type is Linoleic Acid? What does it produce?

What type is Linolenic Acid? What does it produce?

 

  • omega-6 and omega-3
  • Linoleic Acid (18:2 omega-6) -->
    • Arachidonic Acid (20:4 omega-6)
  • Linolenic Acid (18:3 omega-3) --> 
    • Eicosapentanoic Acid (EPA) (20:5 omega-3) and Docosahexanoic acid (DHA) (22:6 omega-3)