FA Metabolism Flashcards
FA synthesis
Acetyl CoA (made in mitochondria via beta-oxidation) enters the cytoplasm, Malonyl CoA generated, which acts as a substrate for FA chain; FA chain formed via FA synthetase
How does acetyl CoA enter the cytoplasm from the mitochondria?
Acetyl CoA condenses with OAA to form citrate (citrate synthase); crosses membrane; citrate broken down to OAA and acetyl CoA via ATP citrate lyase; OAA returned to mitochondria by being converted to malate (malate DH) then to pyruvate (malic enzyme); pyruvate crosses into mit. And conv to OAA via pyruvate carboxylase (requires biotin)
Formation of malonyl CoA
*Rate limiting step of FA synthesis
Acetyl CoA converted to malonyl CoA by addition of CO2 (acetyl CoA carboxylase & biotin)
*malonyl CoA inhibits carnitine acytransferase (FA breakdown)
FA Chain Formation
Malonyl CoA condenses with acetyl CoA (FA synthase) to form palmitate; Acetyl CoA binds to cysteine on FAS & malonyl CoA binds to acyl carrier protein (CO2 lost) (condensation rxn); then reduced, dehydrated, and reduced again; repeated; LOTS of NADPH needed (comes from malic enzyme and PPP)
FA breakdown
Cut 2 C’s at a time till get acetyl CoA; First FA activated with CoA (outer mitochondrial membrane) then beta oxidation in mitochondrial matrix
Beta Oxidation
FA CoA reacts with carnitine (CPT I) to form FA carnitine; can then pass to mitochondrial matrix and is converted back to fatty acyl CoA by CPT II; FA CoA converted to trans fatty enol CoA via acyl CoA (FADH2 formed for ETC); oxidation, hydration, oxidation; final product is acetyl CoA which goes to TCA cycle
What are beta oxidation enzymes called?
Mitochondrial trifunctional proteins
Odd chain FA
Proponyl CoA left; adds carbon by propionyl CoA carboxylase to form methylmalonyl CoA, which is then converted to succinyl CoA and goes to TCA cycle
Unsaturated FA breakdown
Requires isomerase to change position of double bond and reductase to remove double bond
VLCFA
Go to peroxisome for beta oxidation (uses acyl CoA oxidase); forms H2O2; continue till 20 chain then goes to mitochondria
Ketone bodies
Formed in fasted state; ex: acetoacetate, beta hydroxybutyrate, acetone; derived from acetyl CoA; 2 acetyl CoAs form acetoacetyl CoA; conv to HMG CoA via HMG CoA synthase; then to acetoacetate via HMG CoA lyase; acetoacetate spontaneously converted to acetone and to beta hydroxybutyrate via DH
Do RBC’s metabolize ketone bodies?
No
Ketogenic AA
Leu (acetyl CoA and acetoacetate) & Lys (just acetoacetate)
Glucogenic and Ketogenic
Ile Trp Phe Tyr Thr
Glucogenic AA
Val, His, Arg, Asn, Gln, Met, Ala, Asp, Glu, Gly, Pro, Ser, Cys
When is ACC active?
Dephosphorylated; insulin & citrate
