Lipid Metabolism Flashcards
What are the 4 functions of lipids?
- energy storage
- structural components
- Signaling molecules.
- Others: insulation, heat…
What are the types of Fatty Acid Derivatives?
- glycerol backbone (mono-, di- and tri-acylglycerols)
- : 2 fatty acids attached to a glycerol backbone. phosphate esterified with a head group (e.g., phosphatidylcholine, phosphatidylserine)
The other non-FA derivative is isoprenoids (cholestrol/steroids)
What is the Major source of carbon for fatty acid synthesis?
Carbs
What organ does Fatty acid synthesis occur in?
Liver: requires cytosolic and mitochondrial coordination for reactions
What is the foundational unit of FA synthesis?
Acetyl-Coa
What is the first phase of FA synthesis?
Cytosolic entry of Acetyl CoA
Made in mitochondrial matrix but needed in cytoplasm
What is the second phase of FA synthesis?
Generation of Malonyl CoA
Acetyl CoA is carboxylated to malonyl CoA. Most important substrate in FA synthesis. Rate limiting reaction
What is the third phase of FA synthesis?
Fatty acid chain formation
(The enzyme Fatty acid synthase catalyzes 7 reactions that incorporate Acetyl CoA and Malonyl CoA into palmitate, a C16 fatty acid)
What is the rate limiting step of Fatty Acid synthesis?
Acetyl-Coa carboxylase (needs biotin)
What are the activators of ACC?
Citrate, Insulin
What is the reaction that ACC carries out?
ACC carboxylates actetyl-CoA into malonyl-coA and uses 1 ATP and biotin as a cofactor.
What inhibits ACC?
Glucagon, Epinephrine, high AMP, palmitate, PUFA.
Explain the regulation of glucagon and epinephrine involving phosphorylation of ACC and how it affects FA synthesis.
Glucagon and epinephrine cause PKA to PO4 ACC, which INACTIVATES it. INHIBITING ACC = NO FA SYNTHESIS
Explain the regulation of insulin involving phosphorylation of ACC and how it affects FA synthesis.
Insulin stimulates protein phosphatase-1 (PP1) mediated dephosphorylation of ACC, which ACTIVATES IT, thus making FA synthesis on.
What is the Substrate for Fatty Acid Synthase (FAS)
Malonyl-coA
What is the main regulator in FA degradation?
Malonyl-coA
Where does elongation of fatty acids occur?
Smooth ER, uses malonyl-CoA as a carbon donor
Where does desaturation of FAs occur?
Smooth ER, use Acyl-CoA desaturases
How many desaturases do humans have and where can they introduce double bonds?
They can introduce double bonds between carbons 4-5, 5-6, 6-7, and 9-10 of the fatty acid.
FA with double bond beyond carbon 9 and 10 cannot be synthesized in humans
E.g., Omega 3 fatty acids and Omega 6 fatty acids
Need to ingest them or their precursors in diet
Precursors called Essential Fatty Acids
How are desaturases regulated?
Insulin and suppressed by dietary PUFAS (polyunsaturated fatty acids)
What are the essential fatty acids and why can’t they be made?
Linoleic acid (18:2 ω6): used to make arachidonic acid Linolenic acid (18:3 ω3): used to make eicosapentanoic acid (EPA) (20:5 ω3) and docosahexanoic acid (DHA)
What are essential fatty acids?
Human desaturases cannot introduce double bonds beyond C9, which is why they are essential fatty acids.