OUTLINE: DE NOVO SYNTHESIS OF FATTY ACIDS

A. Production of cytosolic acetyl CoA

B. Carboxylation of acetyl CoA to form Malonyl
CoA
C. Fatty Acid Synthase: a multifunctional enzyme
D. Major sources of NADPH
E. Further elongation of fatty acid chains
F. Desaturation of fatty acids

D. Major Sources of NADPH

- NADPH is required for fatty acid synthesis.
- NADPH sources:
1. Hexose monophosphate shunt or the
Pentose phosphate pathway

E. Further elongation of FA chains

- Palmitate can be further elongated
a. Endoplasmic reticulum
b. Mitochondria
c. Brain
- Elongation is by addition of two-carbon units by
separate enzymic processes

F. Desaturation of Fatty Acids

2. Cytosolic malate enzyme
 malate  pyruvate (produces NADPH)
 enzyme: malic enzyme
- conversion of saturated FAs to unsaturated FAs
through addition of double bonds
- enzyme responsible: desaturase
o By nature these enzymes are: mixed
function oxidases
 Oxidases – involves oxygen in
reaction
o Requires NADPH and O2

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OUTLINE: STORAGE OF FATTY ACIDS
A. Structure of Triacylglycerols (TAG)
B. Storage of TAG
C. Synthesis of glycerol phosphate
D. Conversion of a free fatty acid to its
activated form
E. Synthesis of TAG
F. Different fates of TAG

Triacyglycerol (TAG) - storage form of fatty acids

- The presence of unsaturated fatty acids
deceases the melting temperature (Tm) of the
A. Structure of Triacylglycerols (TAG)
lipid.
 Addition of double bonds
decreases the Tm
 Implication in Cell membrane:
Unsaturated fatty acids are component of the
phospholipids in cell membranes and help
maintain membrane fluidity. The “kinks” produced
by double bonds in UFA are responsible for the
membrane’s fluidity. The bending produced by the
double bonds reduces the van der Waals
- Fatty acids are stored as components of interaction between fatty acids; thus, unsaturated
triacylglycerols FAs have lower melting points.

o R: side-chain; hydrocarbon chain
o COO: carboxyl group
o OOC-R: fatty acid chain
o CH2-CH-CH2: glycerol
B. Storage of TAG
- TAGs are stored within Adipocytes
 TAGs are only slightly soluble in water
 They are the major energy reserve of
the body
o FAs can be metabolized to
produce large amounts of
ATP
C. Synthesis of TAG

a. Monoacylglycerol = glycerol + 1 FA 1. Synthesis of glycerol phosphate

b. Diacylglycerol = glycerol + 2 FA  Glycerol - backbone/framework of TAG
c. Triacylglycerol  Glycerol phosphate is the initial
o Glycerol + 3 FAs acceptor o fatty acids during TAG
o Esterified to glycerol through carboxyl synthesis.
groups o Sn-glycerol 3-phosphate
o Loss of negative charge: “Neutral Fat” o Glycerol + phosphate =
glycerol 3-phosphate
- TAGs consist of three fatty acids esterified to (phosphate is attached to
glycerol. carbon 3)
Carbon 1: saturated  There are two pathways for glycerol
Carbon 2: unsaturated phosphate production occurs:
Carbon 3: either a. Liver

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 glycerol  glycerol 3-phosphate
o enzyme: glycerokinase (transfer
phosphate from ATP)

b. Liver and Adipose Tissue

Dihydroxyacetone phosphate (DHAP) --> glycerol

3 – phosphate
o enzyme: G3P dehydrogenase
o DHAP – part of glycolysis*

2. Conversion of a free fatty acid to its activated

form
A fatty acid must first be converted to its
activated form
 Activated form: fatty acyl CoA 4. Different fates of TAG
 enzyme: Fatty acyl CoA TAG has different fates in the liver and adipose
synthetases (thiokinases)
o Requires energy (ATP)

3. Synthesis of TAG
A molecule of TAG is synthesized from glycerol
phosphate and fatty acyl CoA
Four Reactions:
a. Addition of two fatty acids from fatty acyl
CoA
b. Removal of phosphate:
there is no phosphate in TAG
c. Addition of the third fatty acid

tissue
a. Adipose tissue “depot fat”
o TAG is deposited in adipose tissue
o Adipose tissue is also called “depo fat”
it accumulates fat
b. Liver (little TAG stored)
c. Instead, exported and packaged as VLDL
o VLDL – very low density lipoprotein
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OUTLINE: MOBILIZATION OF FATS
A. Release of Fatty Acids from TAG
B. Fate of Glycerol
C. Fate of Fatty Acids
A. Release of Fatty Acids from TAG
- FAs are released from TAGs
- During high energy demands, stored FAs are
mobilized from adipocytes
- Initiated by Hormone-induced Fatty Acid
o Hormone involved: epinephrine
o Lipase: for breakdown/degradation of
lipid
- Mobilization in Adipoctyes:
 Initiated by hormone sensitive lipase:
Hormone sensitive lipase must be activated
 Protein kinase
c. It requires NAPDH derived solely from the
pentose phosphate pathway
d. The pathway is primarily regulated by
isocitrate
e. The pathway does not utilize a carboxyl
reaction
2. An individual has been determined to have
hypertriglyceridemia, with triglyceride level of 350
mg/dL (normal is < 150 mg/dL). The patient decides
to reduce this level by keeping his caloric intake the
same, but switching to a low fat, low protein, high
carbohydrate diet. Three months later, after sticking
faithfully to his diet, his triglyceride level was 375
mg/dL. This increase in lipid content is being caused
by which component of his diet?
A. Phospholipids
B. Triglycerides
C. Amino acids
D. Carbohydrates
E. Cholesterol

Answers:
1. B
2. D

Epinephrine attaches to receptor  receptor enhances

adenylate cyclase  increase in adenylate cyclase 
increase in cAMP  activate PKA  hormone sensitive
lipase is phosphorylated  TAG will release 1 FA
(enzyme: hormone sensitive lipase)  DAG -DAG will
release 1 FA (enzyme: hormone sensitive lipase -> MAG
 MAG will release the last FA (enzyme: MAG lipase) ->
Glycerol (see diagram above)

Checkpoint:
1. The synthesis of fatty acids from glucose in the liver
is best described by which one of the following?
a. The pathway occurs solely in the
mitochondria
b. It requires covalently bound derivative of
pantothenic acid
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