Topic

2: The Polyketide Pathway – Fatty Acids

Contents
Learning Objectives: ....................................................................................................................2
Fatty Acids ...................................................................................................................................3
Malonyl-CoA: ...........................................................................................................................4
Fatty Acid Synthase ................................................................................................................... 4
Fatty Acid Nomenclature ....................................................................................................... 5
Common Unsaturated Fatty Acids .......................................................................................6
Common Saturated Fatty Acids............................................................................................7

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 Learning Objectives:
At the end of this topic you should be able to:

• Be able to write pathway from acetyl CoA to fatty acid compounds.
• Recognize and and appreciate the biological and chemical origins of these
compounds of fatty acid compounds.
• Understand and offer rational mechanistic explanations for some of the key
transformations.
• Understand and appreciate fatty acid nomenclature.

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Fatty Acids

Some characteristics and properties of fatty acids are:
• Amphipathic molecule
• Polar carboxyl group
• Non-polar hydrocarbon tail
• Diverse structures (>100 different types)
• Differ in chain length
• Differ in degree of unsaturation
• Differ in the position of double bonds
• Can contain oxygenated groups

Fatty acids are stored as triacylglycerols.

Example: 3 fatty acid units make the triacylglycerol shown below

• Animal fats contain a high proportion of glycerides of fatty acids and tend to be
solids.
• Plant and fish glyceride contain predominantly unsaturated fatty acids and tend to
be liquids
• Fats and oils represent long term stores of energy for most organisms; being
subjected to oxidative metabolism as required.
• Major oils are produced commercially for use as foods, toiletries, medicines and
pharmaceuticals formulations.

Fatty Acids are thought to be derived from polyketide which in turn are formed from
condensation of acetate (C2) units:

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Malonyl-CoA:
Malonyl CoA (nucleophile) is formed from Acetyl CoA.
Increases acidity of α-proton - and activates it, facilitating Claisen condensation.

Fatty acids, phenols and many aromatic compounds are derived from this pathway.

- Variation in modification of growing chain leads to the variety of structures found.


Fatty Acid Synthase
Fatty Acids are biosynthesized by enzyme Fatty acid Synthase.

Fatty acid Synthase 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 of malonyl-CoA to an acyl carrier protein, followed by a
decarboxylation and condensation reaction that extends the hydrocarbon chain.

Synthetic step involved:

Acetyl-CoA and malonyl-CoA are not directly involved in condensation step.
• They are first converted into enzyme-bound thioesters by means of acyl carrier protein
(ACP).

• This is then followed by, in turn:
- Claisen condensation
- Reduction to alcohol C=O C-OH
- Dehydration to conjugated ester CH-COH C=C
- Reduction of C=C bond C=C C-C

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The next step involve reduction to alcohol, dehydration to conjugated ester and reduction of
C=C

Thus palmitic acid is derived from the following units:

Fatty Acid Nomenclature
Short hand nomenclature describes total number of carbons, number of double bonds and
the position of the double bond(s) in the hydrocarbon tail.

C18:1 D9 = oleic acid, 18 carbon fatty acid with a double bond positioned at the ninth
carbon counting from and including the carboxyl carbon (between carbons 9 and 10)

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1 Acetate + 1 malonate - C4 fatty acid

1 Acetate + 7 malonates - C16 fatty acid (palmitic acid)

1 Acetate + 8 malonates – C18 fatty acid (steric acid)

• Also have unsaturated FA (c=c; c≡ c)

• Fatty acids are mainly found in ester combination with glycerol. These materials are
called fats or oils (glycerides).

Common Unsaturated Fatty Acids

melting point
common name IUPAC name o
(C )
16:0 palmitate hexadeconoate 63
9 9
palmitoleate -0.5
16:1 Δ cis-Δ -hexadeconoate
18:0 stearate octadeconoate 70
9 9
oleate 13
18:1 Δ cis-Δ - octadeconoate
9,12 9,12
linoleate -9
18:2 Δ cis-Δ - octadeconoate
9,12,15 9,12,15
linolenate -17
18:3 Δ cis-Δ - octadeconoate
20:0 arachidate eicosanoate 75
5,8,11,14 5,8,11,14-
20:4 Δ arachindonate cis- Δ eicosatetraenoate -49

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Common Saturated Fatty Acids


common name IUPAC name o
melting point (C )
12:0 laurate dodeconoate 44
14:0 myristate tetradeconoate 52
16:0 palmitate hexadeconoate 63
18:0 stearate octadeconoate 70
20:0 arachidate eicosanoate 75
22:0 behenate docosanoate 81
24:0 lignocerate tetracosanate 84

Some FA natural products are as follows:

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