4th Unit / Ch 16 Fatty Acid & Triglyceride Metabolism Flashcards
Fatty Acid Structure 16 1.1
What term describes molecules such as FAs that have both hydrophobic and
hydrophilic regions, as shown?
The term amphipathic (or amphiphilic ) describes molecules such as FAs that
have both hydrophobic and hydrophilic regions.
Fatty Acid Structure 16 1.2
Which region predominates in Fatty Acids (FAs) 14–20 carbons in length Long Chain Fatty Acids (LCFAs)?
How does
this affect their solubility?
In a LCFA , the hydrophobic region predominates, making it water insoluble. Consequently, LCFAs must be transported through the blood in association with
protein, either on albumin for “free” LCFAs or in Lipo Protein (LP) particles for LCFA esters in
TAG, CEs, and PLs.
[Note: SCFAs and MCFAs are more water soluble than LCFAs.]
Fatty Acid Structure 16 1.3
What does it mean for a FA to be unsaturated? What is the structural meaning of the
designation “ w -6” for an unsaturated FA?
An unsaturated FA has one (monounsaturated) or more (polyunsaturated) double bonds in the cis configuration that causes a kink or bend in the molecule.
If polyunsaturated, the double bonds are spaced at three-carbon intervals. An w -6 unsaturated FA has a double bond six carbons from the methyl ( w ) end, as
shown for arachidonic acid
Fatty Acid Structure 16 1.4
Which FA(s) must be supplied by the diet?
Linoleic acid, an [w -6 FA] and alpha-linolenic acid are not able to be synthesized by humans and are, therefore, required in
the diet. They are essential FAs .
Fatty Acid De Novo Synthesis 16 2.1
In what form are acetate units for FA synthesis transferred from the mitochondrial matrix to the cytosol, as shown? What enzymes are required in the process?
Citrate (made from OAA + acetyl CoA in the
mitochondrial matrix by CS ) is transported across the
inner mitochondrial membrane and cleaved to OAA +
acetyl CoA in the cytosol by ATP–citrate lyase ,
thereby providing acetate units for FA synthesis.
[ Note: No transporter for CoA
(or its derivatives) exists in the membrane.]
Fatty Acid De Novo Synthesis 16 2.2
What is the rate-limiting, regulated step of FA synthesis? How is this step regulated in the short term?
Carboxylation of cytosolic acetyl CoA to malonyl
CoA by ATP- and biotin -requiring Acetyl CoA
carboxylase ACC is the ratelimiting,
regulated step of FA synthesis.
In the short term, ACC is (1) allosterically activated by citrate
and inhibited by LCFA CoAs that promote and prevent,
respectively, the polymerization of ACC protomers
and (2) covalently inhibited by AMPK- catalyzed
phosphorylation as shown.
[Note: AMPK is allosterically activated by AMP. A decrease in the ATP/AMP ratio signals a low-energy state. Acetyl CoA will be oxidized in the TCA cycle (or used for hepatic KB synthesis) rather than be used for FA synthesis under these conditions.]
Fatty Acid De Novo Synthesis 16 2.3
How is the regulated step affected by the drug metformin used in type 2 diabetes ( T2D ) treatment?
Metformin (used in T2D treatment) lowers TAGs by
activating AMPK, thereby inhibiting
Acetyl CoA carboxylase ( ACC) and the synthesis
of FAs needed for TAGs.
[Note: The main effect of metformin is reduction of blood glucose.]
Fatty Acid De Novo Synthesis 16 3.1
The catalytic activities of what multifunctional
enzyme are shown?
Fatty Acid Synthase (FAS) is the multifunctional enzyme.
Fatty Acid De Novo Synthesis 16 3.2
Once a malonyl group (the 2C donor) and
an acetyl group (the first in a series of
2C acceptors) are on the enzyme (steps [1]
to [3], shown), what repetitive sequence of
reactions occurs? What is the end product of
the process?
Once the malonyl 2C-donor and the acetyl 2C-acceptor are
on the enzyme (steps [1] to [3]), the repetitive sequence
catalyzed by FAS is condensation ( decarboxylation )
by 3-ketoacyl-ACP synthase [4],
reduction by NADPH requiring
3-ketoacyl-ACP reductase [5],
dehydration by
3-hydroxyacyl-ACP dehydratase [6],
and reduction by
NADPH-requiring enoyl–ACP reductase [7].
[Note: The ACP domain carries acyl units on its thiol group during FA synthesis.] Palmitic acid (16:0) , released by the
thioesterase activity of FAS , is the primary end product.
Fatty Acid De Novo Synthesis 16 3.3
What are the sources of the NADPH used by
the enzyme?
The NADPH is provided by the PPP and by malic
enzyme, which catalyzes the oxidative decarboxylation of
malate to pyruvate.
Fatty Acid De Novo Synthesis 16 3.4
What is the biochemical basis for some FAs
being nutritionally essential?
Humans are able to elongate and desaturate palmitate to
longer chain–length saturated and unsaturated FAs using
SER enzymes. However, we do not express desaturases
able to introduce double bonds between C-10 and the
w-C. Therefore, we cannot synthesize linoleic and
linolenic acids, and they are dietary essentials.
TAG Storage and Mobilization 16 4.1
What molecule is the initial acceptor of FAs during TAG synthesis, as shown?
Glycerol 3-P is the acceptor. The TAG product has
three FAs esterified to a glycerol backbone.
[ Note: FAs must first be activated to their CoA derivatives
(CoA-FA)
by ATP-dependent fatty acyl CoA synthetases .]
TAG Storage and Mobilization 16 4.2
What are the sources of this molecule in liver, the primary site of TAG synthesis?
In the liver, the primary site of TAG synthesis, glycerol 3-P can be produced from the
(1) reduction of Dihydroxyacetone phosphate (DHAP)
from glycolysis by glycerol 3-phosphate dehydrogenase
and by
(2) phosphorylation of glycerol by
* glycerol kinase* .
TAG Storage and Mobilization 16 4.3
What is the fate of TAGs in liver?
In White Adipose Tissue WAT?
In the liver, TAGs are packaged into LP particles known
as VLDLs and secreted into the blood.
In White Adipose Tissue (WAT), TAGs
are stored as anhydrous cytosolic droplets that represent
the major energy reserve of the body.
TAG Storage and Mobilization 16 4.4
How does the body mobilize TAGs in White Adipose Tissue (WAT) in times of need?
Intracellular TAG lipolysis is catalyzed by lipases including
Hormone Sensitive Lipase HSL that is phosphorylated and activated by Protein Kinase A PKA in
response to epinephrine. The products (3 FAs + glycerol)
are sent into the blood. The FAs are carried on albumin
to target tissues, taken up, and oxidized for energy. The
glycerol is taken up by liver, phosphorylated to glycerol
3-Pby glycerol kinase , and used ingluconeogenesis.