Lecture 7 - Lipids (Part 1)

Definition:
Lipids can be defined as organic substances relatively insoluble in water and
soluble in organic solvents (alcohol, ether etc.).

Functions of lipids: Lipids perform several important functions

1. They are the concentrated fuel reserve of the body (triacylglycerols).
2. Lipids are the constituents of membrane structure and regulate the membrane
permeability (phospholipids and cholesterol) .
3. They serve as a source of fat soluble vitamins (A, D, E and K).
4. Lipids are important as cellular metabolic regulators (steroid hormones and
prostaglandins).

Classifications of Lipids:
1. Simple Lipids:
(a) Fatty acids:
 A fatty acid is water-insoluble long hydrocarbon chain and a terminal
carboxylic acid group. Most fatty acids found in biology have an even
number of carbon atoms, the formula R-COOH, where R is an alkyl
group.
 Fatty acids are rarely found free in nature, but they form parts of many
commonly occurring lipids.

(a) Glycerides:
 Triacylglycerols (also called triglycerides) consist of three fatty acid
chains esterified to a glycerol backbone. Simple triacylglycerols have three
identical fatty acids esterified to the glycerol backbone, while mixed
triacylglycerols have two or three different fatty acid chains.
 Ingested lipids are rich in triacylglycerols (about 90%), these lipids may be
oxidized in the liver to provide energy. Triacylglycerols constitute the
major fuel store and the major dietary lipid in humans.

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  The energy yield from the complete oxidation of fatty acids is about 39
kJ/g, compared with an energy yield of 13 kJ/g of carbohydrate or protein.
 Fats are insoluble in water and stored in specialized cells called adipose
cells (fat cells), mostly in the form of triacylglycerol.
 Triacylglycerols are transported round the body in large lipid–protein
particles called lipoproteins.

Figure 7.1: Structure of triacylglycerol. (a) a simple triacylglycerol (1,2,3-tripalmitoyl-

glycerol), (b) a mixed triacylglycerol (1-palmitoyl-2,3-dioleoyl-glycerol).

2. Compound lipids:
Phospholipids: cellular membrane (details will come later)
Sphingolipids: all human tissues (sphingomyeline)
Glycolipids: Cerebroside
Lipoproteins: HDL and LDL

3. Derived Lipids:
Steroid: derived from cholesterol
Fat-soluble vitamins: Vitamins D, E, A, K

Fatty Acids:
1. Classifications:
a) Based on number of carbon atoms
 Short chain (2-6 C, Acetic acid)
 Medium chain (8-14 C, Capric acid)
 Long Chain (16-26 C, Stearic acid), most common fatty acids containing
16 or 18 carbon atoms.

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 b) Based on structure
 Saturated fatty acids: do not contain double bonds
 Unsaturated fatty acids: contain one or more double bonds

c) Based on source
 Essential they are polyunsaturated fatty acids, including linoleic acid and
linolenic acid. Arachidonic acid (20:4; 5, 8, 11, 14) becomes essential if its
precursor linoleic acid is not provided in the diet in sufficient amounts.
 Nonessential amino acids

2. Nomenclature:
 Numbering of carbon atoms : it starts from the carboxyl carbon which is
taken as number 1. The carbons adjacent to carboxyl carbon are 2, 3, 4 and
so on.

a) Nomenclature of saturated fatty acid:

 Stearic acid (18:0):- means that the number of carbon atoms are 18 and
without double bond – and so on.

b) Nomenclature of the position of double bond in unsaturated fatty acids:

(1) Numeric system or Delta (Δ):
Palmitoleate (palmitoleic acid): - 16:1 (9)
Linoleic acid: - 18:2 (9, 12)
Arachidonic acid: - 20:4 (5, 8, 11, 14)
 Example: C18:1 Δ9 = oleic acid, 18 carbon fatty acid with a double
bond positioned at the ninth carbon including the carboxyl carbon.

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 Figure 7.2: Structures of (A) a saturated fatty acid [Palmitate, (16:0)]; (B)
a monounsaturated fatty acid with a double bond at carbon number 9
[Palmitoleate, C16:1)], and (C) a polyunsaturated fatty acid with 2 double
bonds at C9, 12 [Linoleate (18:2)].

Table 7.1: Fatty acids nomenclature systems

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Table 7.2: Some common important fatty acids

Fatty Acids Synthesis:

 Large fatty acids used by the body are supplied by the diet. Excess amounts of
proteins and carbohydrates obtained from the diet can be converted to acetyl
CoA and then to fatty acids.
 Fatty acid synthesis occurs in liver and lactating mammary glands. It involves
the condensation of acetyl CoA to form long hydrocarbon chains in a series of
reactions. These reactions are carried out on the fatty acid synthase complex
using NADPH and ATP as energy sources.

Transport into the cytosol:

 Fatty acids are synthesized in the cytosol, but acetyl CoA is produced from
pyruvate in the mitochondria
 However, the inner mitochondrial membrane is not readily permeable to this
molecule. This problem is overcome by the condensation of acetyl CoA with
oxaloacetate to form citrate.
 The oxaloacetate, which also cannot cross the inner mitochondrial membrane, is
returned to the mitochondrial matrix through conversion first to malate
(catalyzed by malate dehydrogenase) and then to pyruvate (catalyzed by
NADP+-linked malate enzyme).

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Figure 7.3: Mechanism of Acetyl CoA transport from mitochondria to cytosol.

 The first committed step in fatty acid biosynthesis is the carboxylation of

acetyl CoA to form malonyl CoA using CO2 and catalyzed by acetyl CoA
carboxylase. Biotin is required as a coenzyme, a common feature in CO2-
binding enzymes.

Figure 7.4: Carboxylation of acetyl CoA by

the action of active acetyl CoA carboxylase
enzyme.

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 Fatty acid synthase is the name of the complex of six enzymatic activities that
performs biosynthesis of fatty acids in the cells. The enzyme is composed of two
multifunctional polypeptide chains, which contain the enzymatic activities below:
1. Acetyl-CoA-ACP Transacylase
2. β-Ketoacyl-ACP Synthase
3. Malonyl-CoA-ACP Transacylase
4. β-Ketoacyl-ACP Reductase
5. 3-Hydroxylacyl-ACP Dehydrogenase
6. Enoyl-ACP Reductase

Figure 7.5: Fatty acid synthesis pathway

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 Figure 7.6: The elongation cycle of fatty acid synthesis

Overall equation for palmitic acid synthesis is:

7 Malonyl-CoA + Acetyl-CoA + 14NADPH + 14H+

Palmitic acid + 7CO2 + 14NADP+ + 6H2O + 8CoA

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Formation of double bonds:
 The most common desaturation reactions involve the placement of a double
bond between carbons 9 and 10 in the conversion of palmitic acid to palmitoleic
acid (16:1, ∆9) and the conversion of stearic acid to oleic acid (18:1, ∆9).
 We obtain ω6 and ω3 polyunsaturated fatty acids mainly from dietary plant oils
that contain the ω6 fatty acid linoleic acid (18:2, ∆9, 12) and the ω3 fatty acid
linolenic acid (18:3, ∆9, 12, 15).
 As shown in figure 7.7, the process occurs in the endoplasmic reticulum and
uses molecular oxygen (O2), NADH, and cytochrome b5. Both the fatty acid
and NADH are oxidized. Human desaturases cannot introduce double bonds
between carbons 9 and 10. Therefore, m is equal to or less than 7.

Figure 7.7: Desaturation of fatty acids.