Topic 15: Lipogenesis Flashcards
What do we need for synthesis of Triglycerides?
NADPH comes from: HMPS, Isocitrate Cycle, Malic Enzyme
Acetyl-CoA comes from: Glucose, Amino Acids, and in ruminants Acetate or Beta-Hydroxybutyrate
Glycerol-3-Phosphate or DHAP for glycerol backbone
Where does Fatty Acid Synthesis take place?
CYTOPLASM of Liver, Lactating Mammary Glands, and Adipose
so NOT inside mitochondria
What 2 components make up the Fatty Acid Synthase System?
Acyl Carrier Protein (ACP) Condensing Enzyme (CE)
What is Step 1 of Fatty Acid Synthesis?
2 Carbon Acetyl CoA is combined with HCO3 to make 3 carbon Malonyl CoA via Acetyl-CoA Carboxylase
So, Acetyl CoA –> Malonyl CoA via Acetyl-CoA Carboxylase
Requires an ATP and Bicarb
What vitamin is required for Acetyl-CoA Carboxylase and what is this enzyme’s function?
Need Vitamin B7/Biotin. It is the first step in Fatty Acid Synthesis.
What activates Acetyl-CoA Carboxylase?
Citrate/Isocitrate
What inhibits Acetyl-CoA Carboxylase?
AMP Kinase – phosphorylates it to turn it off
What is Step 2 of Fatty Acid Synthesis?
Malonyl CoA to ACP part of complex
Acetyl CoA to CE part of complex
CONDENSATION - knock of CO2, move Acetyl to Malonyl so everything’s on ACP part – 4 carbons now
Review Slide 7 Lipogenesis
What is Step 3 of Fatty Acid Synthesis?
REDUCTION – take H+ from NADPH (generates NADP+)
Review Slide 7 Lipogenesis
What is Step 4 of Fatty Acid Synthesis?
DEHYDRATION – take off H20
What is Step 5 of Fatty Acid Synthesis?
REDUCTION – take H+ from NADPH (generates NADP+)
Now have Butyrate!
What is Step 6 of Fatty Acid Synthesis?
TRANSFER – move everything to CE part
What is Step 7 of Fatty Acid Synthesis?
RELOAD – put another Malonyl on ACP and repeat the entire process Step 2-6 until you get PALMITIC ACID/PALMITATE (16 C)
What is the only Step that requires ATP in fatty acid synthesis?
Step 1: creating Malonyl CoA from Acetyl CoA
ATP powers Acetyl-CoA Carboxylase
What side of fatty acid chain do you add each set of 2 carbons? Carboxy or Methyl?
Carboxy. So the “oldest” carbons are at the methyl end
Where can mammals desaturate at in fatty acid chains?
from carboxy: 9 then 4, 5, 6, 8
What Desaturase are CATS deficient or completely lacking in?
6-Desaturase - so they can’t Desaturate Linoleic Acid in the pathway to form Arachidonic acid
Where can mammals NOT desaturate past?
9
What is an essential fatty acid for mammals?
Linoleic Acid
alpha-Linolenic Acid
How do we make Arachidonic acid from Linoleic Acid?
Desaturation at 6, Elongation, Desaturation at 5 => Arachidonic acid 20:4 (5,8,11,14)
How is Fatty Acid Synthesis regulated?
Acetyl CoA Carboxylase - forms Malonyl CoA from Acetyl-CoA (Requires B7/Biotin)
STIMULATED by: Citrate or Isocitrate; Protein Phosphatase (via insulin)
INHIBITED by: Palmitoyl CoA (palmitate/palmitic acid) - end product of Fatty Acid Synthesis; Protein Kinase A (via Glucagon)
How do we get Acetyl CoA into the cytoplasm from Mitochondria in NON-ruminants?
Citrate!
Acetyl-CoA + OAA –> Citrate out via transporter –> Citrate via CITRATE LYASE uses an ATP –> Acetyl CoA goes on and OAA has another fate
CoenzymeA DOES NOT MOVE!
How do we replenish OAA in the mitochondria after removing it via citrate for FAS?
OAA via Malate DH (NADH back to NAD+) goes to Malate –> Malate via MALIC ENZYME (NADP+ to NADPH) goes to Pyruvate –> Pyruvate goes on
NAD+ is generated (can now be used for Glycolysis)
NADPH is generated (can now be used for FAS)
How do we get Acetyl CoA into the cytoplasm from Mitochondria in Ruminants?
Acetate absorbed from gut is directly converted to Acetyl-CoA
Simple and boring.
What are the sources of NADPH for FAS?
- HMPS all animals
- Malic Enzyme (Malate -> Pyruvate)
[not so much in Ruminants] - Isocitrate Cycle (Isocitrate -> a-KG via Isocitrate-DH)
[high in ruminants]
[in mito: NAD+ => NADH]
[in cyto: NADP+ => NADPH]
How does Glycerol-3-P and DHAP contribute to Triglyceride synthesis? (now talking about TAG not just fatty acids)
DHAP –> G-3-P via acyltransferase has fatty acid attached to C1 (lysophosphatidic acid) then C2 (PHOSPHATIDIC ACID)
Phosphatidic Acid is Precursor for TAG
CoA is released upon each reaction
Breakdown Non-Ruminant TAG Synthesis.
Aectyl CoA – from Glucose
G-3-P/DHAP – from Glucose
NADPH – HPMS, Isocitrate Cycle, Malic Enzyme
Tissues – many, especially LIVER and ADIPOSE
Breakdown Ruminant TAG Synthesis.
Acetyl CoA – from Acetate/BHBA
G-3-P/DHAP – from Glucose (gluconeogenesis)
NADPH – HMPS, Isocitrate Cycle
Tissues – many, especially ADIPOSE (liver is TOO BUSY doing gluconeogenesis!!)
Does it cost more to build up or breakdown fatty acids?
Always costs MORE to BUILD UP
How much ATP does it cost for FAS?
FAS builds 16 C Palmitic Acid: 7 C-C Cycles 8 ATP used = 8 ATP (to make Malonyl CoA) 14 NADPH = 35 ATP 8 Citrates or Acetates = 8 ATP (takes an ATP to get to Acetyl CoA)
Total = 51 ATP
How much ATP did gluconeogenesis vs glycolysis use/yield?
Gluconeogenesis uses 6 ATP
Glycolysis yields 2 ATP
