Lecture37: Fatty Acid Catabolism Flashcards
What are some sources of fat?
- diet
- stored in cells (adipocytes)
- synthesized in one organ and exported to another
What is the average for the daily energy requirement o humans that is obtained by dietary triacylglycerols?
40%
Where does fatty acid oxidation occur?
in the mitochondrian
Where does beta-oxidation take place?
Eukaryotes- mitochondria and peroxisomes
Bacteria-cytosol
What can the Fatty acyl-CoAs formed on the cytosolic side:
used to synthesize membrane lipids
OR
transported into the mitochondrion
Fatty Acid Transport
Fatty acids with chain lengths of 12 or less can enter without transporters
-greater than 14 and the fatty acid must be transported by carnitine shuttle
Carnitine acyltransferase I
inhibited by malonyl-CoA- the first intermediate in fatty acid synthesis
Oxidation of Fatty Acids
Takes place in three stages
Stage 1 of oxidation of fatty acids
Beta oxidation
- fatty acids undergo oxidative removal of two carbon units in the form of acetyl-CoA starting from the carboxyl end of the fatty acyl chain
- each acetyl-CoA formed requires the removal of two pairs of e- and 4H+ by dehydrogenases
Stage 2 of oxidation of fatty acids
Acetyl-CoA enters the TCA cycle to form CO2, NADH, and FADH2
Stage 3 of oxidation of Fatty acids
the reduced coenzymes (NADH AND FADH2) from stages 1 and 2 are converted to their oxidized form by electron donation to O2 via the ETC (electron transport chain)
-ETC provides the proton gradient and create the proton-motive forced used to make ATP via F0F1ATPase
Reactions of Beta Oxidation
1) oxidation
2) Hydration
3) Further oxidation
4) Thiolysis
Fatty Acid Beta-oxidation multienzyme complex
ECH 2-enoyl-CoA hydratase
HACD L-3-hyroxyacyl-CoA dehydrogenase
-KACT 3-ketoacyl-CoA thiolase
-results in enhanced catalytic efficiency since the active site of each enzyme is positioned in close proximity to the others due to the dimer arrangement. Thus, the ECH and HACD are positioned in a channel and diffuse to the next active site
EXAMPLE EXAMPLE OF METABOLIC CHANNELING
Oxidation of unsaturated fatty acids
- The cis double bonds in fatty acyl chains cannot be acted upon by 2-enoyl-CoA hydrates
- two other enzyme- an isomerase and a reductase-are required
Oxidation of Odd-numbered fatty acids
- processed the same way as the even number fatty acids except they will eventually lead to a 5 carbon acyl chain that will produce acetyl-CoA and Propionyl-CoA
- Acetyl-CoA enters the TCA cycle and propionyl-CoA is metabolized by a three enzyme pathway