David Huffman
Concepts in Biochemistry
Third Edition
Chapter 18:
Metabolism of Fatty Acids
and Lipds
Fats as Fuels
• Fats release a lot of energy
• 38 kJ/gram vs. 16 kJ/gram for carbs
• Carbs (eg., glycogen) is stored with water, about
2-3 gram per gram of glycogen
• Some tissues use fats as the predominant source of
energy -- esp. heart, but also liver, kidney, and
skeletal muscle
• For animals, during hibernation and migration fats
are predominant fuel source.
Sources of Fatty Acids for
Metabolism
• Dietary triacylglycerols and dietary polar
lipids
• Triacylglycerols made in the liver
• Triacylglycerols stored in adipocytes
How we digest lipids -- you need to know this well!
Digestion of Triacylglycerols
• Does not start until they get to small intestine
• Bile salts (below) help emulsify so that
pancreatic lipase can access and hydrolyze the
esters.
• Micelles form in small intestine during this
process. They are made of bile salts, fatty
acids, and mono-, di-, and triacylglycerols, and
other lipids.
Structure of a chylomicron -- other lipoprotein particles
have similar structure
Sizes of lipoprotein particles
Chylomicrons -- one type of
lipoprotein
• Transport exogenous lipids, especially
triacylglycerols
• The chylomicron is assembled, after fatty
acids and other lipids cross intestinal
mucosa, in the lymph system.
• Mature chylomicrons move to capillaries
and are acted upon by lipoprotein lipases
Lipoproteins (the name is a bit
misleading, they are actually particles)
• Made of apolipoproteins, triacylglycerols,
cholesterol, cholesterol esters, and polar lipids.
• Transport lipids in the blood
• 100 mL of human blood has 480 mg of lipids (200
mg cholesterol, 120 mg triacylglycerol, and 160
mg phospholipid)
• The apolipoproteins are amphiphilic helices that
coat the surface of the particle and help make it
soluble (along with the polar lipids).
How fatty acid stores are released from adipocytes -- this is under
hormonal control -- know this!
See page 652-ff for more info
How the lipases work. They hydrolyze the triacylglycerol esters
into free fatty acids and glycerol. The fatty acids can be used for
energy. The glycerol can be used to reassemble fatty acids or
converted into dihydroxyacetone phosphate. The lipases (eg., in
adipocytes is activated by phosphorylation (study this process).
Activation of fatty acids: know where and how this happens,
including the enzymes involved.
The enzyme is Acyl-CoA sythetase
This activation is the first thing that happens after fatty diffuse from
the blood capillaries into the cytoplasm of a cell.
The K’eq of this process is ~1 and pyrophosphate hydrolysis drives it
to completion.
Fatty Acyl-CoA Synthetase -- know this!
In this process two phosphoanhydride bonds are being hydrolyzed
The fatty acyl-CoA cannot cross the
mitochondrial inner membrane!
Activation
Transport
! oxidation
Fatty acid oxidation (breakdown) occurs in the
mitochondria; it is called ! oxidation.
Know steps, enzymes, and cofactors involved in ! oxidation
! oxidation
• How many rounds of ! oxidation would
palmitoyl-CoA undergo?
• As ! oxidation occurs, you are oxidizing the
substrate and placing electrons harvested
into cofactors
How to stay warm in winter -- burn your fat!
Overview of fatty acid oxidation
Go over energy production from palmitate -- Know this; be able to
apply to other fatty acids. Could you draw out the oxidation
reactions for a straight chain fatty acid?
Ketone bodies
• Under certain conditions, ketone bodies can
be produced.
• Ketone bodies are acetoacetate, D-3hydroxybutyrate, and acetone.
• Will hit this again later, but see page 636-7.
This is how we break down unsaturated fat; Don’t have to know this.
How we break down trans fats; don’t have to know this
Breakdown of odd-numbered chain fatty acids. Know this!!
We usually store 3-5 supply of vitamin B12 in liver; deficiency not a
problem usually -- see text for more info.
Know this!
Glucose can also be made into fat, when in excess of need!
Fatty acid synthesis occurs in cytoplasm. How does the acetyl-CoA
from mitochondrion get into the cytosol? Via citrate.
Tricarboxylate translocase
Citrate lyase
Citrate synthase
Malic Enzyme
You know
This one -Page 465
Pyruvate
Translocase
Palmitate is the only product of Fatty Acid Synthase -- this slide
shows origins of carbon atoms in this product. The last two carbons
are directly from acetyl-CoA. The rest are from Malonyl-CoA,
which in fact also arises from Acetyl-CoA.
The Rate-Determining Step of Fatty Acid Synthesis catalyzed by
Acetyl-CoA Carboxylase.
Comparison of CoEnzyme A and ACP -- don’t have to know
structures. You do, however, have to know what these molecules do.
Summary of Steps of Fatty Acid Synthesis
Coordination and Regulation of FA Breakdown and Synthesis.
Very important!
Regulation of FA Metabolism
• Regulation coordinated so that beta oxidation and
synthesis don’t occur at the same time.
• Rate controlling step for beta oxidation is entry of
fatty acids into mitochondria. Enzyme is
Carnitine Acyl Transferase I
• Rate controlling step of FA synthesis is activity of
Acetyl-CoA Carboxylase
• Know how metabolites affect the activity of these
enzymes
Know this and it’s enzyme target, HMG-CoA reductase.
First steps of cholesterol synthesis. Know!
Cytosolic
HMG-CoA
Rate-controlling step
Cholesterol is synthesized in the cytoplasm of
liver cells.
See fate of HMG-CoA in mitochondria on
page 637.
Not required to know.
Not required to know, but do know that squalene is an intermediate.
Squalene monooxygenase is an ironcontaining enzyme.
Cholesterol is used to make many different essential molecules.
Know the structure and function of lipoproteins! Read and
comprehend pages 584-587 with regard to lipoproteins.
How cholesterol is taken up into cells.