Fatty acid degradation

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CHAPTER 27: Fatty Acid
Degradation
(Problems: 1,6,8,9,11,12,14,17-21,23,31)
1. Mobilization of lipids. Degradation
of TAGs to FAs and glycerol.
2. Activation of Fas.
3. Oxidation of FAs to acetyl-CoA,
and processing by CAC.
27.1: Fatty Acids are Processed in
Three Stages

Lipase Hydrolysis of TAGs
Perilipin: mobilization of TAGs, and release of ATGL co-activator (CA). ATGL: Adipose triglyceride lipase. Hydrolysis of one FA from TAG to produce DAG
+ FA.
HS-lipase: Hormone sensitive lipase. Hydrolysis of FA from DAG to produce MAG +
FA.
MAG lipase: Hydrolysis of remaining FA from MAG to produce glycerol and FA.

Liver
Distribution of FAs and Glycerol
In blood via
serum
albumin.

Activation of FAs
Fatty acyl CoA
Equivalent to the hydrolysis of 2 ATP.
2 Pi
Acyl CoA synthetase

Transport to Mitochondria

-oxidation cycle
1
4
3
2
CH
3
SCoA
O
AcCoA
NADH
FADH
2
AcCoA
NADH
FADH
2
AcCoA
NADH
FADH
2
AcCoA
NADH
FADH
2
AcCoA
NADH
FADH
2
AcCoA
NADH
FADH
2
AcCoA
NADH
FADH
2
AcCoA
Total: 8 AcCoA + 7 NADH + 7 FADH
2
Fatty Acid Oxidation

Activiation
Transport
Oxidation 1
Hydration
Oxidation 2
Thiolysis
-Oxidation Cycle

Net yield of ATP per palmitate oxidized to 16 CO
2
ATP generated
8 acetyl CoA 80
7 QH
2
10.5
7 NADH 17.5
108 ATP
ATP expended to activate palmitate -2
Net yield: 106 ATP
Glc (6 C) = 32 ATP which is 5.33 ATP/C
PA (16 C) = 106 ATP which is 6.88 ATP/C

27.2: Degradation of Unsaturated and
Odd-Chain Fatty Acids
-oxidation cycle
1
4
3
2
3 rounds -
oxidation
Skips one FAD →FADH
2
step
Unsaturated Fatty Acids

Skips one FAD →
FADH
2
step
Skips one FAD →
FADH
2
step
Adds one FADH
2
Uses one “NADH”
equivalent
Summary: -1 FADH
2
, -1 NADH

Odd-Chain Fatty Acids
5 ATP
1 ATP
1.5 ATP
2.5 ATP
How many ATPs would result from oxidiation of heptadecanoic acid?

27.3: Ketone Bodies
Acetoacetate
3-Hydroxybutyrate
Acetone
Water soluble
Easily transportable
Synthesis in liver

27.4: Physiological Conditions and
Fatty Acid Metabolism
Diabetes
Starvation
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