Download Chapter 21 - Evangel University

Mary K. Campbell
Shawn O. Farrell
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Chapter 21
Lipid Metabolism
Paul D. Adams • University of Arkansas
Generation and Storage of Energy
• The oxidation of fatty acids (FA)in triacylglycerols is the
_________________________________ for most organisms
• Their carbon chains are in a highly reduced form
• The energy yield per gram of fatty acid oxidized is greater
than that per gram of carbohydrate oxidized
Catabolism of Lipids
• ____________ catalyze
hydrolysis of bonds
between fatty acid and
the rest of
triacylglycerols
• __________________
catalyze hydrolysis of
bonds between fatty
acid and the rest of
phosphoacylglycerols
• May have multiple sites
of action
Fatty Acid Activation
• Fatty acid oxidation begins with ____________
• 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
• The acyl-CoA crosses the ____________
mitochondrial membrane, but not the ____________
membrane
• The acyl group is then transferred to carnitine,
carried across the inner mitochondrial membrane,
and transferred to mitochondrial CoA-SH
• Carnitine Palmitoyltransferase (CPT-1) has
specificity for acyl groups between 14 and 18
carbons long
The Role of Carnitine in Acyl-CoA Transfer
-Oxidation
• -Oxidation: a series of reactions that cleaves
carbon atoms __________ 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
Summary
• Fatty acids are activated and transported to the
mitochondrial matrix for further catabolism
• The breakdown of fatty acids takes place in the
mitochondrial matrix and proceeds by successive
removal of two-carbon units as acetyl-CoA
• Each cleavage of a two-carbon moiety requires a
four-step reaction sequences called -oxidation
Energy Yield from FA Oxidation
• The energy released by the oxidation of acetyl-CoA
formed by -oxidation of FA can drive ___ synthesis
• ____________ cycles of -oxidation are required for
the oxidation of stearic acid to acetyl-CoA
Energy Yield from FA Oxidation
• The overall equation for oxidation of stearic acid
can be obtained by adding the equations for
-oxidation, the ______________________, and
___________________________________
Energy Yield from FA Oxidation
Summary
• The complete oxidation of FA by the citric acid
cycle and the electron transport chain releases
large amounts of energy
• When we include the reoxidation of NADH and
FADH2 from -oxidation and the citric acid cycle,
we obtain a net yield of 120 ATP for a single
molecule of stearic acid
Catabolism of 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
_______________
_______________
Oxidation of an Unsaturated FA
• A cis-trans isomerization is needed to convert
unsaturated FA to acetyl-CoA
• This enzyme is known as an ______________
• Oxidation of unsaturated FA does not generate
as much ATP relative to saturated FA with the
same # of carbons
Oxidation of an Unsaturated FA
Summary
• FA with odd number of carbons produce
propionyl-CoA in the last step of the oxidation
• Propionyl-CoA can be converted to succinylCoA, which plays a role in the citric acid cycle
• The oxidation of unsaturated FA requires
enzymes that catalyze isomerization around the
double bonds so that oxidation can proceed
Ketone Bodies
• Formation of ketone bodies occurs when the amount
of acetyl-CoA produced is excessive compared to
the amount of oxaloacetate available to react with it
• Intake high in _______ and low in ______________
• Diabetes not suitably controlled
• Starvation
• Ketone bodies are: acetone, -hydroxybutyrate,
and acetoacetate
• Formed principally in ___________ mitochondria
• Can be used as a fuel in most tissues and organs
Ketone Bodies
Summary:
• If an organism has an
excess of acetyl-CoA, it
produces ketone bodies.
• This situation can arise from
an excessive intake of fats
compared to carbohydrates,
or from diabetes.
Fatty Acid Biosynthesis
• Biosynthesis is not
exact reversal of
oxidation
• Biosynthetic
reactions occur in
the ___________
Fatty Acid Biosynthesis
• Carboxylation of acetyl-CoA occurs in the cytosol
• Catalyzed by acetyl-CoA carboxylase
• ___________ is the carrier of the carboxyl group
• Malonyl-CoA is key intermediate that is produced
Biosynthesis of Palmitate
Sites of Fatty Acid Metabolism in an Animal Cell
Summary
• Acetyl-CoA is transported to the cytosol and converted to
malonyl-CoA
• The biosynthesis of FA proceeds by the addition of 2-carbon
units to the hydrocarbon chain.
• The process is catalyzed by the fatty-acid synthase complex
Comparison of FA Degradation and Biosynthesis
Triacylglycerol Biosynthesis
Lipids such as
triacylglycerols,
phosphoacylglycerols,
and steroids are
derived ___________
__________________
Biosynthesis of Phosphoacylglycerols
Biosynthesis of Sphingosine/Ceramide
Requires
starting materials
_______________
and serine
Cholesterol Biosynthesis
• All carbon atoms of cholesterol and
steroids synthesized from it are derived
from the two-carbon acetyl group of
___________________
• Involves many reaction steps
• Involvement of ___________ units are
key to the biosynthesis of steroids and
other biomolecules known as ________
Overall View of Cholesterol Biosynthesis
Cholesterol Biosynthesis
• Synthesis begins with the
condensation of 2 molecules
of __________________
• Next, condensation with a
3RD molecule of __________
• The formation of mevalonate
is completed by reduction of
the thioester to a 1° alcohol
Mevalonate to Squalene
• The pyrophosphosphorylation of the 1° alcohol of mevalonate
(two moles of ATP) is followed by phosphorylation of the 3°
alcohol (one mole of ATP), then the concerted
decarboxylation and -elimination of phosphate ion gives
______________________ ______________________
• Then there is an enzyme-catalyzed isomerization of the
carbon-carbon double bond that gives dimethylallyl
pyrophosphate
• Dimethylallyl pyrophosphate is then converted to isopentyl
pyrophosphate, which is followed by H+ loss to give farnesyl
pyrophosphate
• The joining together of two units of farnesyl pyrophosphate
(C15) units by a 2-electron oxidation gives ___________ (C30)
The Conversion of Mevalonate to Squalene
Squalene to Cholesterol
Cholesterol as a Precursor
Cholesterol is the precursor
for a number of
______________________
______________________
Role of Cholesterol in Heart Disease
• Lipids are transported in the blood stream by
______________________
• Cholesterol and its fatty acid esters are packaged
into several classes of lipoproteins for transport
The LDL Particle
The Fate of Cholesterol
Summary
• The biosynthesis of cholesterol proceeds by the
condensation of five-carbon isoprenoid units
• Isoprenoid units in turn are derived from the reaction
of three acetyl-CoA units
• Once cholesterol is formed, it serves as a precursor
for other steroids
• Cholesterol must be packaged for transport in the
bloodstream. Some of these forms of cholesterol
play a role in heart disease