Lect 6 Lipid Synthesis Flashcards
3 Main Functions of Lipids
Fuel Store (Energy)
Structural Component (PM)
Signaling Molecules
Major Source of C for FA Synthesis?
Dietary CHO
What is the main FA Synthesis Location?
Where can it also take place?
Primarily Liver
Adipose, Brain, Kidney, Lactating Mammary Glands
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 (-)
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 (-)
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)
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 (-)
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
- Each has 7 enzyme activities and Acyl Carrier Protein (ACP)
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
What are the Reactions Catalyzed by FAS
- 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)
What are the Sources of NADPH During FA Synthesis
Malic Enzyme: 1
PPP: 2-12
Regulation of ATP Citrate Lyase (Phase I)
Activate: Phosphorylation, Glucose, Insulin
Inhibitors: Polyunsaturated FAs (PUFAs), Leptin
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)
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
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
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
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)
Desaturase Regulation
Where in FA does cholesterol induce desaturase?
- Activated: Insulin
- Inhibited: dietary PUFAs
- Dietary cholesterol induces C9-10 desaturase, inhibits all others
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)