9 - Fatty acid modifications

Question 1

Describe the three rules of polyunsaturated fatty acid nomenclature

Answer 1

(i) Δ terminology – numbered from the carboxyl end of acyl chain e.g. linoleic acid has double bonds between carbons 9 and 10 and between carbons 12 and 13. This fatty acid is designated as C18:29,12. The enzymes that create the double bonds are the Δ9 and Δ12 desaturases, respectively.
(ii) n- or ω- terminology – identifies only the first double bond from the methyl end of the acyl chain. Thus, oleic acid is a member of the n-9 or -9 series of fatty acids, whereas, linoleic acid is a member of the n-6 or ω-6 family and linolenic acid is a member of the n-3 or ω-3 family.

(iii) Relationship between the Δ and n- nomenclature. To fully describe a fatty acid, both of the nomenclatures should be used. As an example, consider linolenic acid which has 18 carbons and 3 double bonds (C18:3). It is a member of the n-3 fatty acid family and the first double bond is 3 carbons from the methyl group. From the carboxyl end, this double bond would be between carbons 15 and 16. Thus, this is designated as Δ15. The other two double bonds are designated as Δ9 and Δ12. Linolenic acid is therefore designated C18:3 (n-3) Δ9,12,15.


Question 2

Give the names for the cis oleic acid and trans isomer, elaidic acid.

Answer 2

C18:1(n-9) cΔ9

C18:1(n-9) tΔ9

Question 3

How does chain length of fatty acids correlate to melting point?

Answer 3

Longer chains melt at a higher temperature (increases melting point)

Increasing number of double bonds decreases the melting point (becomes ‘kinked’ with less hydrogen saturation)

Question 4

Animals cannot introduce double bonds into the fatty acyl chain beyond C10. Since most fatty acids are C16, C18 or longer, n-3 and n-6 fatty acids are not synthesized by animals. How do animals acquire these fatty acids?

Answer 4

Plants synthesize fatty acids that contain double bonds closer to the methyl end of the acyl chain, including the n-3 and n-6 species.

These are acquired in the diet of animals and are ESSENTIAL.

Eg. needed for synthesis of things like arachidonic acid, which is the precursor for the eicosanoids.

Question 5

How can the primary product of fatty acid synthesis (palmitate) be changed?

Answer 5

It can be elongated in increments of two carbon units or desaturated

Desaturation can occur by the enzymes:
Δ9 desaturase
Δ6 desaturase
Δ5 desaturase

However some of these enzymes are present at very low levels, so some very long chain polyunsaturates are more effectively obtained in the diet

Question 6

Describe fatty acid desaturation in animals. What do desaturases use as substrate and what stimulates them?

Answer 6

Δ9 desaturation of stearate to oleate and of palmitate to palmitoleate Catalysed by fatty acyl CoA desaturase system, which is located on
the cytoplasmic surface of the endoplasmic reticulum

Requires 3 membrane proteins and NAD(P)H and uses fatty acyl-CoA as substrate

Both the fatty acyl CoA and the NAD(P)H undergo oxidation (mixed function oxidases, because two substrates undergo simultaneous 2-electron oxidations)

Desaturases all use fatty acyl-CoA as substrate and are stimulated by insulin (insulin-stimulated desaturation promotes storage)

Question 7

Describe fatty acid desaturation in plants

Answer 7

In plants, there are Δ6, Δ9 , Δ12 and Δ15 desaturases that use phospholipid as substrate and occurs on the fatty acid at the sn-2 position

Question 8

Where does fatty acid elongation occur? What are used as fatty acid carriers?

Answer 8

Fatty acid synthase produces palmitate

Elongation of acyl chain occurs in mitochondria and on the endoplasmic reticulum (ER)

ER has the majority of elongating activity

Sequence of reactions is similar to fatty acid synthase but has different enzymes and uses acyl-CoA derivatives as carriers (rather than as thioesters with ACP)

Question 9

Give the steps of fatty acid elongation in the ER

Answer 9

1. condensation of the long chain acyl-CoA substrate with malonyl-CoA, catalysed by one of two condensing enzymes, specific for either saturated or unsaturated acyl substrate
2. the β-ketoacyl-CoA is reduced by NADPH, dehydrated and reduced again by NADPH to give a saturated fatty acid, two carbons longer than the original substrate

Question 10

How does mitochondrial fatty acid elongation differ from ER elongation

Answer 10

Mitochondrial system uses acetyl-CoA, instead of malonyl-CoA as source of 2C units

Question 11

What are eicosanoids and what do they originate from?

Answer 11

Exert specific effects on target cells, just like hormones
however, unlike hormones, their actions are confined to the local environment near the site of synthesis and are catabolized extremely rapidly after exerting action

All originate from eicosenoic acids (eg. arachidonic acid)

Arachidonic acid is released from the sn-2 position of membrane phosphatidylcholine by a phospholipase A2 activity

Question 12

Describe eicosanoid synthesis

Answer 12

Arachidonic acid undergoes modification in either the cyclo- oxygenase or the lipoxygenase pathway to form active prostaglandins or leukotrienes, respectively

Question 13

What are COX inhibitors?

Answer 13

Inhibition of the cyclo-oxygenase pathway by aspirin (acetylsalicylic acid) or ibuprofen reduces prostaglandin levels (which mediate pain sensation) and thromboxane levels (which mediate blood clotting)

Salicylate acts by covalent acetylation of the enzyme PGH synthase

NSAIDs mimic the substrate or a reaction intermediate for COX