Lect 6 Lipid Synthesis

Question 1

3 Main Functions of Lipids

Answer 1

Fuel Store (Energy)

Structural Component (PM)

Signaling Molecules

Question 2

Major Source of C for FA Synthesis?

Answer 2

Dietary CHO

Question 3

What is the main FA Synthesis Location?

Where can it also take place?

Answer 3

Primarily Liver

Adipose, Brain, Kidney, Lactating Mammary Glands

Question 4

What occurs in Phase I FA Synthesis

Cytosolic Entry of Acetyl CoA

What is ATP Citrate Lyase Regulated By?

Answer 4

• 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 (-)

Question 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?

Answer 5

• 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 (-)

Question 6

Malonyl CoA is the substrate for what enzyme?

What does it regulate and why is it important?

Answer 6

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

Question 7

What occurs in FA synthesis Phase III - FA Chain Formation

How is FA Synthase regulated?

Answer 7

• 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 (-)

Question 8

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

How many proteins in each dimer?

Answer 8

• 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

Question 9

Describe the Palmitate Synthesis Reaction

How many rounds are completed?

Answer 9

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

7 Rounds

Question 10

What are the Reactions Catalyzed by FAS

Answer 10

• Condensation: Acetyl CoA (2C) + Malonyl CoA (3C) –> 4C and release CO₂
• Reduction: NADPH –> NADP⁺
• Dehydration: H₂O Removed
• Reduction: NADPH –> NADP⁺
• Repeat 6 more times (7 total) –> Palmitate (16C)

Question 11

What are the Sources of NADPH During FA Synthesis

Answer 11

Malic Enzyme: 1

PPP: 2-12

Question 12

Regulation of ATP Citrate Lyase (Phase I)

Answer 12

Activate: Phosphorylation, Glucose, Insulin

Inhibitors: Polyunsaturated FAs (PUFAs), Leptin

Question 13

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

Allosteric Inhibitors?

What causes phosphorylation?

What causes dephosphorylation?

Answer 13

• 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)

Question 14

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

What increases and decreases activity?

Answer 14

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

Question 15

Leptin: Fat-Brain Axis

Where does it come from?

How does it work and where does it go?

Answer 15

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

Question 16

Longer Chain FA Synthesis - Elongation

Where does this occur? Distinctions?

Answer 16

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

Question 17

Desaturation means what?

What catalyzes this reaction?

Which locations can humans introduce double bonds?

Answer 17

• 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)

Question 18

Desaturase Regulation

Where in FA does cholesterol induce desaturase?

Answer 18

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

Question 19

Essential FAs include what type?

What type is Linoleic Acid? What does it produce?

What type is Linolenic Acid? What does it produce?

Answer 19

• 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)