Digestion and absorption of fats

The major fats in the diet are triacylglycerols and, to a lesser extent, phospholipids. These are hydrophobic molecules and have to be emulsified to very small droplets (micelles; section 4.3.2.2) before they can be absorbed. This emulsification is achieved by hydrolysis to monoacyl- and diacylglycerols and free fatty acids, and also by the action of the bile salts (section 4.3.2.1).

4.3.1 The classification of dietary lipids

Four groups of compounds that are metabolically important can be considered under the heading of lipids:

• Triacylglycerols (sometimes also known as triglycerides), in which glycerol is esterified to three fatty acids (Figure 4.10). These are the oils and fats of the diet, inside cell ¡mucosal cell membrane intestinal lumen Na+

Na pump and Na/K ATPase

Na pump and Na/K ATPase glucose + galactose

glucose + galactose maltose maltase J^

lactase trehalase trehalase glucose + glucose lactose ^ glucose + galactose

trehalose glucose + glucose carrier-mediated passive diffusion

"DC

se IL

sucrose \

fructose monosaccharides sugar alcohols

Figure 4.9 The hydrolysis of disaccharides and absorption of monosaccharides.

which provide between 30% and 45% of average energy intake (section 7.3.2). The difference between oils and fats is that oils are liquid at room temperature, whereas fats are solid.

  • Phospholipids, in which glycerol is esterified to two fatty acids, with a phosphate and a hydrophilic group esterified to carbon-3 (section 4.3.1.2). Phospholipids are major constituents of cell membranes.
  • Steroids, including cholesterol and a variety of plant sterols and stanols (section 7.5.1) and extremely small amounts of steroid hormones (section 10.4). Chemically these are completely different from triacylglycerols and phospholipids, and are not a source of metabolic fuel.
  • A variety of other compounds, including vitamin A and carotenes (section 11.2), vitamin D (section 11.3), vitamin E (section 11.4) and vitamin K (section 11.5).

O H2C—O— C—(CH2)n—CH3 CH3—(CH2)n—C—O—CH

Figure 4.10 The structure of triacylglycerol and types of fatty acids.

polyunsaturated fatty acid (linoleic acid, C18:2 w 6)

Figure 4.10 The structure of triacylglycerol and types of fatty acids.

They are absorbed in lipid micelles (section 4.3.2.2), and adequate absorption depends on an adequate intake of fat.

4.3.1.1 Fatty acids

There are a number of different fatty acids, differing in both the length of the carbon chain and whether or not they have one or more double bonds (—CH = CH—) in the chain (see Figure 4.10). Those with no double bonds are saturated fatty acids — the carbon chain is completely saturated with hydrogen. Those with double bonds are unsaturated fatty acids — the carbon chain is not completely saturated with hydrogen. Fatty acids with one double bond are known as monounsaturated, whereas those with two or more double bonds are known as polyunsaturated.

Although it is the fatty acids that are saturated or unsaturated, it is common to discuss saturated and unsaturated fats. Although is not really correct, it is a useful shorthand, reflecting the fact that fats from different sources contain a greater or lesser proportion of saturated and unsaturated fatty acids.

As shown in Table 4.1, there are three different ways of naming the fatty acids:

• Many have trivial names, often derived from the source from which they were originally isolated — thus oleic acid was first isolated from olive oil, stearic acid from beef tallow, palmitic acid from palm oil, linoleic and linolenic acids from linseed oil.

CH2

OH

HO CH

CH2

OH

glycerol

Table 4.1 Fatty acid nomenclature

Carbon atoms

Double bonds Number

First

Shorthand

Saturated

Butyric

4

0

-

C4:0

Caproic

6

0

-

C6:0

Caprylic

8

0

-

C8:0

Capric

I0

0

-

CI0:0

Lauric

I2

0

-

CI2:0

Myristic

I4

0

-

CI4:0

Palmitic

I6

0

-

CI6:0

Stearic

I8

0

-

CI8:0

Arachidic

20

0

-

C20:0

Behenic

22

0

-

C22:0

Lignoceric

24

0

-

C24:0

Monounsaturated

Palmitoleic

I6

I

6

CI6:I ra6

Oleic

I8

I

9

CI8:I ra9

Cetoleic

22

I

II

C22:I ra II

Nervonic

24

I

9

C24:I ra9

Polyunsaturated

Linoleic 18 2

a-Linolenic 18 3

y-Linolenic 18 3

Arachidonic 20 4

Eicosapentaenoic 20 5

Docosatetraenoic 22 4

Docosapentaenoic 22 5

Docosapentaenoic 22 5

Docosahexaenoic 22 6

Polyunsaturated

Linoleic 18 2

a-Linolenic 18 3

y-Linolenic 18 3

Arachidonic 20 4

Eicosapentaenoic 20 5

Docosatetraenoic 22 4

Docosapentaenoic 22 5

Docosapentaenoic 22 5

Docosahexaenoic 22 6

CI8:2 ra6 CI8:3 ra3 CI8:3 ra6 C20:4 ra6 C20:5 ra3 C22:4 ra6 C22:5 ra3 C22:5 ra6 C22:6 ra3

  • All have systematic chemical names, based on the number of carbon atoms in the chain and the number and position of double bonds (if any).
  • A shorthand notation shows the number of carbon atoms in the molecule, followed by a colon and the number of double bonds. The position of the first double bond from the methyl group of the fatty acid is shown by n- or W- (the W-carbon is the furthest from the a-carbon, which is the one to which the carboxyl group is attached; W (omega) is the last letter of the Greek alphabet).

In the nutritionally important unsaturated fatty acids, the carbon—carbon double bonds are in the or-configuration (see Figure 2.5). The trans-isomers of unsaturated fatty acids do occur in foods to some extent, but they do not have the desirable biological actions of the cis-isomers, and indeed there is some evidence that trans-fatty acids may have adverse effects. As discussed in section 7.3.2.1, it is recommended that the consumption of trans-unsaturated fatty acids should not increase above the present average 2% of energy intake.

Polyunsaturated fatty acids have two main functions in the body:

  • as major constituents of the phospholipids in cell membranes (section 4.3.1.2);
  • as precursors for the synthesis of a group of compounds known as eicosanoids, including prostaglandins, prostacyclins and thromboxanes. These function as local hormones (paracrine agents), being secreted by cells into the extracellular fluid and acting on nearby cells.

The polyunsaturated fatty acids can be interconverted to a limited extent in the body, but there is a requirement for a dietary intake of linoleic acid (C18:2 w6) and linolenic acid (C18:3 W3), as these two, which can each be considered to be the precursor of a family of related fatty acids and eicosanoids, cannot be synthesized in the body.

As discussed in section 7.3.2.1, an intake of polyunsaturated fatty acids greater than needed to meet physiological requirements may confer benefits in terms of lowering the plasma concentration of cholesterol and reducing the risk of atherosclerosis and ischaemic heart disease. The requirement is less than 1% of energy intake, but it is recommended that 6% of energy intake should come from polyunsaturated fatty acids.

High intakes of the long-chain W-3 polyunsaturated fatty acids (as found in fish oils) may additionally provide protection against thrombosis, as they form the 3-series eicosanoids, which inhibit platelet cohesiveness.

4.3.1.2 Phospholipids

Phospholipids are, as their name suggests, lipids that contain a phosphate group. As shown in Figure 4.11, they consist of glycerol esterified to two fatty acids, one of which (esterified to carbon-2 of glycerol) is a polyunsaturated fatty acid. The third hydroxyl group of glycerol is esterified to phosphate. The phosphate, in turn, is esterified to one of a variety of compounds, including the amino acid serine (section 4.4.1), ethanolamine (which is formed from serine), choline (which is formed from ethanolamine), inositol (section 10.3.3) or one of a variety of other compounds.

A phospholipid lacking the group esterified to the phosphate is known as a phosphatidic acid, and the complete phospholipids are called phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine (also called lecithin), phos-phatidylinositol, etc.

As shown in Figure 4.12, phospholipids form a lipid bilayer, with the hydrophobic fatty acid chains inside and the hydrophilic groups outside. This is the basic structure of cell membranes; various proteins may be embedded in the membrane at one surface

o

Major water-soluble groups in phospholipids ch2— ch— nh3+ ch2-ch2— nh3+ coo-

phosphatidylserlne phosphatidylethanolamine

Figure 4.11 The structure of phospholipids.

or the other, or may span the membrane (transmembrane proteins) as either transport proteins (section 3.2.2) or receptors for hormones and neurotransmitters (section 10.3.1). The polyunsaturated fatty acids esterified at carbon-2 of glycerol in phospholipids are essential for membrane fluidity; neither saturated fatty acids nor the trans-isomers of polyunsaturated fatty acids will pack to form an adequately fluid membrane. Other lipids, including cholesterol (section 4.4.3.1.3) and vitamin E (section 11.4), are dissolved in the hydrophobic interior of the membrane and are essential to its function.

In addition to its structural role, phosphatidylinositol has a specialized function in membranes, acting as the source of inositol trisphosphate and diacylglycerol, which are produced as intracellular second messengers in response to fast-acting hormones and neurotransmitters (section 10.3.3).

4.3.1.3 Cholesterol and the steroids

As can be seen from Figure 4.13, steroids are chemically completely different from triacylglycerols or phospholipids. The parent compound of all the steroids in the body is cholesterol; different steroids are then formed by replacing one or more of the hydrogens with hydroxyl groups or oxo-groups, and in some cases by shortening the side-chain.

ho oh ho oh phosphatidylcholine phosphatidylinositol (lecithin)

transmembrane protein (e.g. a receptor)

intracellular membrane protein

Figure 4.12 The arrangement of phospholipids in cell membranes.

transmembrane protein forming a transport pore outside intracellular membrane protein

Figure 4.12 The arrangement of phospholipids in cell membranes.

inside

Figure 4.13 Cholesterol and some steroid hormones.

Apart from cholesterol, which is important in membrane structure and the synthesis of bile salts (section 4.4.3.2.1), the steroids are slow-acting hormones (section 10.4). Vitamin D (section 11.3) is a derivative of cholesterol, and can also be considered to be a steroid hormone.

The cholesterol that is required for membrane synthesis, and the very much smaller amount that is required for the synthesis of steroid hormones, may either be synthesized in the body or provided by the diet; average intakes are of the order of 500 mg (1.3 mmol)/day.

An elevated plasma concentration of cholesterol (in low-density lipoproteins) is a risk factor for atherosclerosis and ischaemic heart disease. As discussed in section 7.3.2.1, the dietary intake of cholesterol is less important as a determinant of plasma cholesterol than is the intake of total and saturated fat, or the intake of compounds that inhibit the reabsorption of cholesterol secreted in bile, or the reabsorption of bile salts themselves (section 4.3.2.1).

4.3.2 Digestion and absorption of triacylglycerols

The digestion of triacylglycerols begins with lipase secreted by the tongue; as discussed in section 1.3.3.1, lingual lipase may be important in permitting the detection of fat in the diet, and hence in determining food choices. It continues in the stomach, where gastric lipase is secreted. As shown in Figure 4.14, hydrolysis of the fatty acids esterified to carbons 1 and 3 of the triacylglycerol results in the liberation of free fatty acids and 2-monoacylglycerol. These have both hydrophobic and hydrophilic regions, and will therefore emulsify the lipid into increasingly small droplets. Triacylglycerol hydrolysis continues in the small intestine, catalysed by pancreatic lipase, which requires a further pancreatic protein, colipase, for activity. Monoacylglycerols are hydrolysed to glycerol and free fatty acids by pancreatic esterase in the intestinal lumen and intracellular lipase within intestinal mucosal cells.

4.3.2.1 Bile salts

The final emulsification of dietary lipids into micelles (droplets that are small enough to be absorbed across the intestinal mucosa) is achieved by the action of the bile salts. The bile salts are synthesized from cholesterol in the liver, and secreted, together with phospholipids and cholesterol, by the gall bladder. As shown in Figure 4.15, some 2 g of cholesterol and 30 g of bile salts are secreted by the gall bladder each day, almost all of which is reabsorbed, so that the total faecal output of steroids and bile salts is 0.2-1 g/day.

The primary bile salts (those synthesized in the liver) are conjugates of chenodeoxycholic acid and cholic acid with taurine or glycine (Figure 4.16). Intestinal bacteria catalyse deconjugation and further metabolism to yield the secondary bile

O II

O H2C—O—C—(CH2)n—CH3 CH3—(CH2)n—C—O—¿H triacylglycerol H2é—O—C—(CH2)n—CH3

CH3—(CH2)n —C—O—CH diacylglycerol H2è—O—C—(CH2)n—CH3

H20 e

CH3—(CH2)n—COOH O H2C—OH CH3—(CH2)n—[[—O—¿H monoacylglycerol H2è—OH

( pancreatic esterases v. and intracellular lipase

Figure 4.14 Lipase and the hydrolysis of triacylglycerol.

salts, lithocholic and deoxycholic acids. These are also absorbed from the gut, and are reconjugated in the liver and secreted in the bile.

Both cholesterol and the bile salts can be bound physically by non-starch polysaccharide (section 4.2.1.6) in the gut lumen, so that they cannot be reabsorbed. This is the basis of the cholesterol-lowering effect of moderately high intakes of non-starch polysaccharide (section 7.3.3.2) — if the bile salts are not reabsorbed and reutilized, then there will be further synthesis from cholesterol in the liver, so depleting body cholesterol.

Under normal conditions, the concentration of cholesterol in bile, relative to that of bile salts and phospholipids, is such that cholesterol is at or near its limit of solubility.

Figure 4.15 Cholesterol and bile salt metabolism.

glycochenodeoxycholic acid glycocholic acid taurochenodeoxycholic acid taurocholic acid glycochenodeoxycholic acid glycocholic acid taurochenodeoxycholic acid taurocholic acid

0 H

0 H H

\ JÒ—N—b—COO"

l H H H

glycine conjugates

taurine conjugates

Figure 4.16 The metabolism of bile salts.

Figure 4.16 The metabolism of bile salts.

It requires only a relatively small increase in the concentration of cholesterol in bile for it to crystallize out, resulting in the formation of gallstones. Obesity (section 6.2.2) and high-fat diets (especially diets high in saturated fat, which increase the synthesis of cholesterol in the liver) are associated with a considerably increased incidence of gallstones. Figure 4.17 shows the increased risk of developing gallstones with increasing obesity.

<24 24.5 25.5 26.5 28 29.5 32.5 37.5 42.5 >45

Figure 4.17 The incidence of gallstones with obesity {body mass index = weight (in kg)/height (in m)2; the desirable range is 20—25}. From data reported by Stampfer MJ et al., American Journal of Clinical Nutrition 55: 652-658, 1992.

<24 24.5 25.5 26.5 28 29.5 32.5 37.5 42.5 >45

Figure 4.17 The incidence of gallstones with obesity {body mass index = weight (in kg)/height (in m)2; the desirable range is 20—25}. From data reported by Stampfer MJ et al., American Journal of Clinical Nutrition 55: 652-658, 1992.

4.3.2.2 Lipid absorption and chylomicrons

The finely emulsified lipid micelles, containing free fatty acids with small amounts of intact triacylglycerol, monoacylglycerol, phospholipids, cholesterol and fat-soluble vitamins (see Chapter 11) are absorbed across the intestinal wall into the mucosal cells. Here, fatty acids are re-esterified to form triacylglycerols (see Figure 5.28), and are packaged together with proteins synthesized in the mucosal cells to form chylomicrons. These are secreted into the lacteal in the centre of the villus (see Figure 4.2), and enter the lymphatic system, which drains into the bloodstream at the thoracic duct. See section 5.6.2.1 for a discussion of the metabolism of chylomicrons and other plasma lipoproteins.

In the fed state, in response to the action of insulin (section 10.5) lipoprotein lipase is active at the surface of cells in adipose tissue. It catalyses the hydrolysis of triacylglycerols in chylomicrons, and most of the resultant free fatty acid is taken up by adipose tissue for re-esterification to triacylglycerol for storage. The chylomicron remnants are taken up by the liver, by a process of receptor-mediated endocytosis (section 5.6.2), and most of the residual lipid is secreted, together with triacylglycerol synthesised in the liver, in very low-density lipoproteins (section 5.6.2.2).

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