FATTY ACID METABOLISM

Structure of Fats and Triglycerides

Fatty Acid

Triglycerides
FATTY ACID
Transport of Fatty Acid
 β-Oxidation of Fatty Acids
• Lipases catalyze
hydrolysis of bonds
between fatty acid and
the rest of
triacylglycerols
• Phospholipases
catalyze hydrolysis of
bonds between fatty acid
and the rest of
phosphoacylglycerols
• May have multiple sites of
action
• Happens inside the
mitochondria
The β-carbon

Carbonyl Carbon

β-carbon

α-carbon
 Fatty Acid Activation
• Fatty acid oxidation begins with activation
• A thioester bond is formed between the
carboxyl group of the FA and the thiol of CoA-
SH
The Role of Carnitine in Acyl-CoA Transfer
Overview of -Oxidation of Fatty
Acids
 -Oxidation of Fatty Acids
• -Oxidation: a series of reactions that cleaves
carbon atoms two at a time from the carboxyl
end of a fatty acid
• The complete cycle of one -oxidation requires
four enzymes
• Reaction 1: Oxidation of the , carbon-carbon single
bond to a carbon-carbon double bond
• Reaction 2: Hydration of the carbon-carbon double
bond
• Reaction 3: Oxidation of the -hydroxyl group to a
carbonyl group
• Reaction 4: Cleavage of the carbon chain by a reverse
Claisen reaction
-Oxidation of Stearic Acid Gives
Rise to Nine 2-Carbon Units
 What is the net ATP yield of
β-oxidation of stearic acid?
8 cycles of β-oxidation:
8 NADH x 2.5 ATP/NADH ------------------------------------> 20 ATP
8 FADH2 x 1.5ATP/ FADH2 -----------------------------------> 12 ATP
9 acetyl CoA

9 acetyl CoA enters the Kreb’s Cycle

9 acetyl CoA x 3 NADH/acetyl CoA x 2.5ATP/NADH --> 67.5 ATP
9 acetyl CoA x 1 FADH2/acetyl CoA x 1.5ATP/FADH2 -> 13.5 ATP
9 acetyl CoA x 1 GTP/acetyl CoA x 1ATP/GTP --------> 9 ATP
Total 122 ATP
- 2 ATP
120 ATP
 Catabolism of Unsaturated FA and
Odd-Numbered FA
• Odd-numbered FA are
not frequently
encountered, but do
also undergo -
oxidation

• The last -oxidation

cycle of a fatty acid
with an odd number of
carbons gives
propionyl-CoA
OXIDATION OF
UNSATURATED
FATTY ACID
 Fatty Acid Biosynthesis

• Biosynthesis is not
exact reversal of
oxidation

• Biosynthetic reactions
occur in the cytosol
 Fatty Acid Synthesis
• an anabolic pathway which utilizes “excess”
acetyl CoA to produce medium and long chain
of fatty acid
• Utilizes a complex enzyme system fatty acyl
synthase which is like a factory system which
assembles fatty acid
Synthesis of Malonyl CoA
Addition of 2C in Fatty Acid
Synthesis
SYNTHESIS OF FATTY ACID
GLUCONEOGENESIS AND
KETOGENESIS
Overview of Glucose Metabolism
 Gluconeogenesis

Gluconeogenesis is the process whereby precursors

such as lactate, pyruvate, glycerol, and amino acids
are converted to glucose.
Fasting requires all the glucose to be synthesized from
these non-carbohydrate precursors.
Most precursors must enter the Krebs cycle at some
point to be converted to oxaloacetate.

Oxaloacetate is the starting material for

gluconeogenesis
 Gluconeogenesis is not just the reverse of
glycolysis

Several steps are different so that control of one

pathway does not inactivate the other. However
many steps are the same. Three steps are different
from glycolysis.
1 Pyruvate to PEP
2 Fructose 1,6- bisphosphate to Fructose-6-phosphate
3 Glucose-6-Phosphate to Glucose
CATABOLISM OF AMINO ACIDS
SYNTHESIS OF
GLUCOSE FROM
AMINO AND
OTHER
METABOLIC
INTERMEDIATES
KETOGENSIS
END