BCH210H1 Lecture Notes - Lecture 36: Carnitine O-Palmitoyltransferase, Adenylyl Cyclase, Carnitine

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BCH210 Lecture 30 Fat catabolism
Fat mobilization via beta-adrenergic signaling
Epinephrine or glucagon binds to GPCRs on adipose cells
Signaling response activates a cascade:
o G-alpha-GTP activates adenylyl cyclase
o Adenylyl cyclase produces cAMP
o cAMP activates PKA
PKA activates hormone sensitive lipase (HSL) by phosphorylating them
TAG is hydrolyzed to 3 fatty acid chains that are released into the blood and transported
via albumin because they are not soluble
Glycerol is also produced from TAG hydrolysis
Fatty acid activation
- Fatty acids that are delivered to cells are activated and trapped in the cell by covalently
attaching CoA
- Acyl CoA synthetase uses ATP and CoA to form acyl CoA
o PPi and AMP are released
- the acyl CoA synthetase reaction is reversible
o pyrophosphate hydrolysis helps drive the reaction forward by converting PPi to 2
Pi
- AMP is not energetically efficient
o Normally ADP is used to produce ATP
o To produce ATP from AMP we need to convert AMP to ADP using a second ATP
o Therefore, fatty acid activation by CoA requires 2 ATP
Acyl CoA and beta-oxidation
- Acyl CoA is made in the cytoplasm, but beta-oxidation takes place in the mitochondrial
matrix
- Acyl CoA can pass through the outer membrane into the intermembrane space, but it
cannot cross the inner membrane because it is too large and there is no transport
mechanism
o The inner membrane is not permeable to most substances
Carnitine shuttle
- The shuttle is made up of 2 reversible carnitine acyltransferases and a translocase
- Carnitine acyltransferase I (CAT I) creates acyl carnitine from acyl CoA, which is then
transported across the inner membrane in exchange for a carnitine done by the
translocase
- Carnitine acyltransferase II (CAT II) regenerates fatty acyl CoA inside the matrix
- Acyl CoA can now be used by mitochondrial beta-oxidation to generate more ATP
NOTE: there are two pools of CoA, one in the cytosol and one in the matrix and these two pools
never mix!
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