TAGs & beta-oxidation

L20 fat metabolism

How does hormone signals fatty acid chain release?

• epinephrine & glucose signal via GPCRs on adipose cells

• involves: Ga-ATP release → adenylyl cyclase activation → cAMP production → PKA activation → phosphorylates & activates triacylglycerol lipase → hydeolyzes ester bonds to produce free fatty acids & glycerols

• FFAs are transported in blood via albumin for cellular use

acyl-CoA vs. acetyl-CoA?

Acyl-CoA:

• broad term, any FA conjugated to CoA via thioester linkage

Acetyl-CoA:

• 2C acyl CoA

How does fatty acid activation occur in cytoplasm? what’s needed?

• after entering cells from bloodstream, acyl chains are trapped to prevent diffusion back out by forming covalent thioester bond with CoA

  • catalyzed by Acyl CoA Synthetase

  • reversible reaction, uses ATP → AMP + PPi

  • PPi hydrolysis makes this reaction favorable

  • to use AMP, it must be converted to ADP by sacrificing a 2nd ATP

→ Fatty acid activation by CoA requires 2ATP (1 for activation, 1 for ADP production) & 1H2O to hydrolyze PPi

where does acyl-CoA & β-oxidation occur?

acyl-CoA = cytoplasm
β-oxidation = matrix

How is acyl-CoA transported into matrix?

via Carnitine Shuttle (CoA is hydrophilic)

• temporarily transfers acyl group to carnitine (can cross membrane)

• shuttle has 3 components:

  • carnitine acyltransferase I (CAT1)

  • translocase (antiporter)

  • carnitine acyltransferase II (CATII)

• CATI moves acyl chain onto carnitine from CoA

• translocase moves acyl-carnitine in, free carnitine out

• CATII moves acyl chain back onto CoA

• acyl-CoA can then be catabolized in β-oxidation

how to calculate the number of rounds needed in β-oxidation?

#of rounds = (number of carbon/2) - 1

which carbon does fatty acid oxidation occur on?

β-carbon (3rd C)

TCA is dependent on the amount of ___ present

oxaloacetate

how many enzymes are needed in beta-oxidation?

4