Chapter 17:
Oxidation of Fatty Acids
keystone concepts
• The insolubility of triglycerides in dietary lipids and adipose
tissue must be accommodated
• Fatty acids are oxidized in the mitochondria
• Fatty acids must be transported across the inner mitochondrial
membrane
• Oxidation of fatty acids in the mitochondria has three stages
• Oxidation of unsaturated and odd chain fatty acids requires
additional reactions
• In mammals, an alternative pathway for acetyl-CoA produces
ketone bodies
1
Emulsification
• Fats are not water soluble
• Made soluble by bile salts (amphipathic) that
are made in the liver and stored in the gall
bladder
• Converted to mixed micelles of bile salts and
triacylglycerols
How are dietary lipids processed?
3
Fat Metabolism
I’m not fat, I’ve just got a lot of potential energy!
Fatty Acids and Energy
• Fatty acids in triglycerides are the principal
storage form of energy for most organisms.
– Hydrocarbon chains are a highly reduced form of
carbon.
– The energy yield per gram of fatty acid oxidized is
greater than that per gram of carbohydrate
oxidized.
Beta Oxidation
The break down of a fatty acid to acetyl-CoA
units…the ‘glycolysis’ of fatty acids
STRICTLY AEROBIC
Occurs in the mitochondria
Acetyl-CoA is fed directly into the Krebs cycle
Activation and Transported to
Mitochondria
• FA + CoA + ATP  fatty acyl-CoA + AMP + 2Pi
• Coupled to the cleavage of ATP
• Acyl CoA Synthetase – a family of isozymes
specific for short, medium and long chain FA that
catalyze production of fatty acyl-CoA
• Transported through inner mitochondrial
membrane via carnitine
– uses specific acyl carnitine transporter
Beta Oxidation
• Breakdown of fats into
– Acetyl coenzyme A --> Krebs Cycle
– FADH2 --> Oxidative Phosphorylation
– NADH--> Oxidative Phosphorylation
• Breaks off two carbons at a time to acetyl CoA
-oxidation –
first of three stages
of fatty acid
oxidation
9
4 Steps of -oxidation
1.
Dehydrogenation of the fatty acyl-CoA
to make a trans double bond between α
and β carbon.
•
•
Short, medium, and long chain acyl-CoA
dehydrogenases
e- removed transferred to FAD
2.
Hydration of the double bond
1.
Dehydrogenation of the -hydroxyl
group to a ketone
- e- removed transferred to NAD+
1.
Acylation – addition of CoA and
production of acetyl-CoA
Step 1
Step 2
Step 3
Step 4
10
Energy Yield from -Oxidation
• Yield of ATP per mole of stearic acid (C18).
Step Chemical Step
Happens ATP
1
Activation (stearic
acid -> stearyl CoA)
Once
-2
2
Oxidation (acyl CoA ->
trans-enoyl CoA)
produces FADH2
8 times
16
4
Oxidation (hydroxy-
8 times
24
Oxidation of acetyl CoA
9 times
by the common metabolic
pathway, etc.
TOTAL
108
acyl CoA to ketoacyl
CoA) produces NADH +H+
146
Ketone Bodies
• Ketone bodies: acetone, -hydroxybutyrate, and
acetoacetate;
– are formed principally in liver mitochondria.
– can be used as a fuel in most tissues and organs.
• Formation occurs when the amount of acetyl CoA
produced is excessive compared to the amount of
oxaloacetate available to react with it and take it
into the TCA; for example:
– intake is high in lipids and low in carbohydrates.
– diabetes is not suitably controlled.
– starvation.
ketone bodies:
another fate for acetyl-CoA
•
•
•
•
Formed in the liver
Exported
Oxidized in citric acid cycle
Step 1: thiolase reversed – joins 2
acetyl-CoA
• Step 2: acetyl-CoA condensation
• Step 3: cleavage of acetyl-CoA
• Step 4: reduction or
decarboxylation
13
ketone bodies provide energy
14
Amino acid oxidation
keystone concepts:
• Dietary proteins - primary source of biologically useful N in
animals
• Amino groups transferred to α-ketoglutarate forming
glutamate and an α-keto acid
• Deaminated amino acids produce carbon skeletons that
enter the citric acid cycle
• Most amino acids are glucogenic, some are both glucogenic
and ketogenic,
just 2 are solely ketogenic
15
amino acid oxidation
• How much energy do organisms derive from amino acids?
• That depends upon the organism
Carnivores (~90% after a meal)
Humans (10-15%)
• What distinguishes amino acid catabolism from the oxidative
processes discussed thus far?
• Every amino acid contains an amino group; amino acid
16
oxidation produces high quantities of toxin: Ammonia – NH4+
N balance = Nin - Nout
1. AA are used for Protein Synthesis & N containing
compounds
2. AA in excess are degraded (used for energy)
N is disposed of in urea (80%) or creatinine
Positive Nitrogen Balance
Negative Nitrogen Balance
1. Stress
2. Decreased Intake
3. Lack of an essential AA
we cannot make essential amino acids
20
Metabolic Pool of Amino Acids
• Metabolic pool AA has no storage form in mammals (as with other life
forms) as free AA or as specialized storage form (such as glycogen
for glucose, TG for FA) but a certain percentage of muscle &
structural proteins are “expendable”.
• AA are used for proteins, N compounds, energy (also via glucose)
but increased protein breakdown will eventually compromise normal
protein function.
• Therefore need a small mobile pool of free AA in cells and blood
Dietary protein
is degraded to
amino acids
Proteases in the stomach
and small intestine
Peptidases at the intestinal
mucosa
22
Protein Catabolism
Overview of Protein catabolism.
first step in amino acid oxidation
•
•
•
•
•
Removal of the amino group
Formation of an a-keto acid
How?
Aminotransferases (transaminases)
Collects the amino groups from many amino acids in
the form of L-glutamate  amino group carrier
24
nitrogen excretion: urea cycle
25
Amino Acid Catabolism
• The breakdown of amino acid carbon
skeletons follows two pathways.
– glucogenic amino acids: those whose carbon
skeletons are degraded to pyruvate or
oxaloacetate, both of which may then be
converted to glucose by gluconeogenesis.
– ketogenic amino acids: those whose carbon
skeletons are degraded to acetyl CoA or
acetoacetyl CoA, both of which may then be
converted to ketone bodies.
Major Functions of Amino Acids
Derived from Dietary Protein
Oxidation
Glycogenic amino acids: --Blood glucose--Energy
Ketogenic amino acids: -Acetyl CoA-Stored fat-Energy
Biosynthesis of nitrogen-containing metabolites
Heme
Choline
Glycosamine
Nucleotides
Blood cell
PL
Sugar
DNA
Protein synthesis
Biogenic amines
Protein
Neurotransmitters
Carnitine
Heart
Creatine phosphate « Energy »
Amino Acid Catabolism
• Catabolism of AA carbon skeletons.
Amino Acid Catabolism
Glucogenic
Aspartate
Asparagine
Alanine
Glycine
Serine
Threonine
Cysteine
Glutamate
Glutamine
Arginine
Proline
Histidine
Valine
Methionine
Glucogenic
Ketogenic and Ketogenic
Leucine
Isoleucine
Lysine
Phenylalanine
Tryptophan
Tyrosine