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Fatty acid #2
Fatty acid #3
Lipid Metabolism
Lipid Metabolism
Pathway Questions
1. What purpose does fatty acid metabolism serve in animals?
Fatty acid oxidation in mitochondria is responsible for providing
energy to cells when glucose levels are low. Triacylglycerols
stored in adipose tissue of most humans can supply energy to
the body for ~3 months during starvation.
Fatty acid synthesis reactions in the cytosol of liver and adipose
cells convert excess acetyl CoA that builds up in the
mitochondrial matrix when glucose levels are high into fatty
acids that can be stored or exported as triacylglycerols.
Pathway Questions
2. What are the net reactions of fatty acid degradation and
synthesis for the C16 fatty acid palmitate?
Fatty acid oxidation:
Palmitate + 7 NAD+ + 7 FAD + 8 CoA + 7 H2O + ATP
8 acetyl CoA + 7 NADH + 7 FADH2 + AMP + 2 Pi + 7 H+
Fatty acid synthesis:
8 Acetyl CoA + 7 ATP + 14 NADPH + 14 H+
Palmitate + 8 CoA + 7 ADP + 7 Pi + 14 NADP+ + 6 H2O
Pathway Questions
3. What are the key enzymes in fatty acid metabolism?
Fatty acyl CoA synthetase enzyme catalyzing the "priming" reaction in
fatty acid metabolism which converts free fatty acids in the cytosol into
fatty acyl-CoA using the energy available from ATP and PPi hydrolysis.
Carnitine acyltransferase I - catalyzes the commitment step in fatty acid
oxidation which links fatty acyl-CoA molecules to the hydroxyl group of
carnitine. The activity of carnitine acyltransferase I is inhibited by malonylCoA, the product of the acetyl-CoA carboxylase reaction, which signals
that glucose levels are high and fatty acid synthesis is favored.
Pathway Questions
3. What are the key enzymes in fatty acid metabolism?
Acetyl CoA carboxylase - catalyzes the commitment step in fatty acid
synthesis using a biotin-mediated reaction mechanism that carboxylates
acetyl-CoA to form the C3 compound malonyl-CoA. The activity of acetyl
CoA carboxylase is regulated by both reversible phosphorylation (the
active conformation is dephosphorylated) and allosteric mechanisms
(citrate binding stimulates activity, palmitoyl-CoA inhibits activity).
Fatty acid synthase - this large multi-functional enzyme is responsible for
catalyzing a series of reactions that sequentially adds C2 units to a
growing fatty acid chain covalently attached to the enzyme complex. The
mechanism involves the linking malonyl-CoA to an acyl carrier protein,
followed by a decarboxylation and condensation reaction that extends the
hydrocarbon chain.
Pathway Questions
4. What are examples of fatty acid metabolism in real life?
A variety of foods are prominently advertised as "non-fat," even though they
can contain a high calorie count coming from carbohydrates. Eating too
much of these high calorie non-fat foods (e.g., non-fat bagels) activates the
fatty acid synthesis pathway resulting in the conversion of acetyl-CoA to
fatty acids, which are stored as triacylglycerols.
-oxidation yields
large amounts of ATP
The energy conversion
process of fatty acid --> ATP
involves oxidation of fatty
acids by sequential
degradation of C2 units
leading to the generation
FADH2, NADH, and acetyl
CoA.
Palmitate
(C16)
-oxidation reactions
OXIDATION
HYDRATION
OXIDATION
THIOLYSIS
Ketogenesis
When fatty acid oxidation produces more
acetyl-CoA than can be combined with
OAA to form citrate, then the "extra"
acetyl-CoA is converted to acetoacetylCoA and ketone bodies, including
acetone. Ketogenesis (synthesis of
ketone bodies) takes place primarily in the
liver.
Ketogenesis
Acetyl-CoA derived from fatty acid oxidation enters
the Citrate Cycle only if carbohydrate metabolism
is properly balanced.
When fatty acid oxidation produces more acetylCoA than can be combined with OAA to form
citrate, then the "extra" acetyl-CoA is converted to
acetoacetyl-CoA and ketone bodies, including
acetone. Ketogenesis (synthesis of ketone bodies)
takes place primarily in the liver.
20 ATP
Ok, now what
happens to these
two acetyl-CoA?
per Acetyl-CoA
PowerPoint slide from lecture 28