Flashcards in Lipid Metabolism Deck (18):
glycerol backbone + FA
glycerol backnone + 2 FAs + phosphate head group
Phase 1 of FA synthesis
Cytosolic Entry of Acetyl CoA: in the mitochondrial matrix, OAA + acetyl CoA can be converted to citrate, which can then be shuttle out of mitochondria into cytosol where it can be converted back to OAA via ATP citrate lyase. (+ glucose and insulin, - leptin and PUFA). As citrate is converted back to OAA, CoA + ATP is converted back to Acetyl-CoA to enter FA synthesis. OAA can then be converted back to malate and reenter mitochondria there or go to pyruvate and reeneter mitochondria.
Phase II of FA synthesis
Now acetyl CoA is free in cytoplasm. Acetyl CoA -> Malonyl CoA via Acetyl CoA carboxylase (ACC).
Rate limiting step of FA synthesis and coenzyme
ACC! and Biotin (B7)
Activators and inhibitors of ACC
Active when dephosphorylated and inactive when P
+: insulin (activates PPI), citrate (allosterically)
-: PUFA (allosterically), glucagon (PKA), epinephrine (PKA), high AMP (activates AMP kinase)
Malonyl CoA inhibits what?
Carnitine acyltransferase (rate limiting step for FA degradation)
Phase III of FA synthesis
Two units of Malonyl CoA are added to growing fatty acyl chain in 7 reactions to form palmitate (16:0) via Fatty acid synthase.
Structure of FA synthase
7 enzymatic subunits and acyl carrier protein (ACP)
Stoichiometry of Palmitate synthesis
1 acetyl CoA + 7 malonyl CoA + 14 NADPH + 14 H+ = Palmitate + NADP + 8 CoA + 6 H20
Reactions of FA synthase
Condensation, Reduction, Dehydration, Reduction X 6
Then product release
Regulation of ATP Citrate Lyase
Stimulated by Phosphorylation. Gene expression is induced by glucose and insulin. PUFAs and Leptin counteract gene expression.
Regulation of FA synthase
Insulin, glucocorticoid hormones, and high carb/low fat diet increase synthesis.
High fat diets and high PUFA suppress synthesis.
Leptin is secreted in direct proportion to fat mass that acts on leptin receptor in hypothalamus. When fat mass is high leptin is secreted to suppress food intake
Elongation of Palmitate occur where ?
Smooth ER or mitochondria and uses NADPH as reducing power. SER uses malonyl CoA as carbon donor and Mitochondria uses Acetyl CoA as carbon doner
How is desaturation done?
By Acyl CoA desaturases: humans have 4 - ∆4, ∆5, ∆6, and ∆9. FA's with double bonds beyond carbon 9 and 10 cannot be synthesized in humans -> essentail FA such omega 3 and omega 6 FA.
Regulation of Desaturases
Insulin induces gene expression and PUFAs suppress expression.