Digestion And Absorption

To be usable by the body, dietary fats must be digested in the lumen of the small intestine. The digestion products pass through the gut wall and are resynthesized in the intestinal epithelial cells and packaged for transport in the bloodstream.

5.1.1 Intestinal digestion of dietary fats involves breakdown into their component parts by a variety of digestive enzymes

Typically 90-95% of fat in the human diet is provided by triacylglycerols, with smaller contributions from phospholipids and cholesterol. The dietary triacylglycerols must be partially hydro-lysed before the body can assimilate them.

At birth, the new-born animal has to adapt to the relatively high fat content of breast milk after relying mainly on glucose as an energy substrate in foetal life. It is presented with two major problems in fat digestion: the pancreatic secretion of lipase is rather low and the immature liver is unable to provide sufficient bile salts to solubilize the digested lipids. These problems are even more acute in the premature infant. Yet the new-born baby can digest fat, albeit less efficiently than the older child or adult. There are two mechanisms that allow this to occur. Breast milk contains a lipase that is stimulated by bile salts, known as bile-salt stimulated lipase (BSSL). Milk also contains lipoprotein lipase, although this is not thought to play a role in fat digestion. BSSL may assist the neonate in digesting the milk triacylglycerols. In addition, the neonate secretes a triacylglycerol lipase from glands in the stomach. This is an acid lipase, with a pH optimum of around 4-6, although it is still active even at a pH of 1. In other mammals a homologous lipase may be secreted higher up the gastrointestinal tract - from the serous glands of the tongue in rodents (lingual lipase) and from the pharyngeal region in ruminants. The realization that humans (neonatal and adult) secrete a gastric lipase is relatively recent, and there are still references to human lingual lipase in the literature.

The products of these lipases are mainly 2-monoacylglycerols, diacylglycerols and non-ester-ified fatty acids, the latter being relatively richer in medium-chain length fatty acids than the original acylglycerols. The milk fat of most mammals is relatively rich in medium-chain length fatty acids (8C-12C) rather than the usual 16C and 18C fatty acids. The relative ease with which lipids containing medium-chain fatty acids can be absorbed certainly helps lipid uptake in babies. Human milk triacylglycerols (along with those of some other mammals including pigs) have a predominance of palmitic acid esterified at position 2. This will lead to the production of 2-palmitoylglycerol, which is readily absorbed (see below). Since the absorption of saturated (non-esterified) fatty acids (which are solid at body temperature unless emulsified, Section 2.1.1) may be less efficient that that of unsatu-rated fatty acids, the structure of human milk triacylglycerols seems to be a way of optimizing absorption of palmitic acid.

As the baby is weaned onto solid food, the major site of fat digestion shifts from the stomach to the duodenum. Gastric lipase continues to play a role, however, even into adulthood. It has been estimated that gastric lipase is responsible for 25% of the partial triacylglycerol hydrolysis necessary for absorption to occur. In addition, the action of gastric lipase seems to produce lipid droplets that are better substrates for the later action of pancreatic lipase. The stomach also plays a role with its churning action, creating a coarse oil-in-water emulsion, stabilized by phospholipids. Also, proteolytic digestion in the stomach serves to release lipids from the food particles where they are generally associated with proteins. The acidic fat emulsion that enters the duodenum from the stomach is neutralized and modified by mixing with bile and pancreatic juice. Bile supplies bile salts that in humans are mainly the glycine and taurine conjugates of tri- and di-hydroxycholanic acids (usually known as cholic and chenodeoxycholic acid), formed from cholesterol in the liver (Section 7.5.6) and phospholipids. Much of the intestinal phospholipid in humans is of biliary origin and is estimated at between 7 and 22 g day"1 compared with a dietary contribution of 4-8 g day"1. Biliary secretion is enhanced by the enzyme cholecysto-kinin, secreted from the duodenal mucosa, in response to entry of the acidic mixture from the stomach (chyme) into the duodenum. Pancreatic juice, whose secretion is also stimulated by chole-cystokinin, supplies bicarbonate to neutralize the acidic chyme, and enzymes that catalyse the hydrolysis of fatty acids from triacylglycerols, phospholipids and cholesterol esters (Fig. 5.1).

In most adults the process of fat digestion is very efficient and the hydrolysis of triacylglycerols is mainly accomplished in the small intestine by a triacylglycerol lipase secreted from the pancreas, pancreatic lipase. This enzyme is related to lipoprotein lipase and hepatic lipase (Section 3.5.2). Pancreatic lipase attacks triacylglycerol molecules at the surface of the large emulsion particles (the oil-water interface), but before lipolysis can occur, the surface and the enzyme must be modified to allow interaction to take place. Firstly, bile salt molecules accumulate on the surface of the lipid droplet, displacing other surface-active constituents. As amphipathic molecules they are

Lipid Digestion The Small Intestine

Fig. 5.1 The digestion and absorption of dietary fat in the small intestine. Lipid droplets entering the small intestine from the stomach are subjected to the action of pancreatic lipase, phospholipase A2 and cholesterol esterase, which hydrolyse triacylglycerol (TAG) to produce monoacylglycerols (MAG) and fatty acids (FA), phospholipids (PL) to produce lysophospholipids and fatty acids; and cholesterol esters (CE) to liberate cholesterol (C) and fatty acids. These are emulsified with bile salts (from the gall bladder) to produce a micellar suspension (the mixed micelles) from which components are absorbed across the epithelial cell (enterocyte) membranes. Short- and medium-chain fatty acids pass through into the circulation (into the hepatic portal vein), and bile salts are reabsorbed, along with further cholesterol, in the lower part of the small intestine. Within the enterocyte, the components are reassembled, and packaged into chylomicrons, the largest of the lipoprotein particles (see Fig. 5.4 for further details of this process). The chylomicrons are secreted into small branches of the lymphatic system, the lacteals.

Fig. 5.1 The digestion and absorption of dietary fat in the small intestine. Lipid droplets entering the small intestine from the stomach are subjected to the action of pancreatic lipase, phospholipase A2 and cholesterol esterase, which hydrolyse triacylglycerol (TAG) to produce monoacylglycerols (MAG) and fatty acids (FA), phospholipids (PL) to produce lysophospholipids and fatty acids; and cholesterol esters (CE) to liberate cholesterol (C) and fatty acids. These are emulsified with bile salts (from the gall bladder) to produce a micellar suspension (the mixed micelles) from which components are absorbed across the epithelial cell (enterocyte) membranes. Short- and medium-chain fatty acids pass through into the circulation (into the hepatic portal vein), and bile salts are reabsorbed, along with further cholesterol, in the lower part of the small intestine. Within the enterocyte, the components are reassembled, and packaged into chylomicrons, the largest of the lipoprotein particles (see Fig. 5.4 for further details of this process). The chylomicrons are secreted into small branches of the lymphatic system, the lacteals.

adapted for this task since one side of the rigid planar structure of the steroid nucleus is hydrophobic and can essentially dissolve in the oil surface. The other face contains hydrophilic groups that interact with the aqueous phase (Fig. 5.2). The presence of the bile salts donates a negative charge to the oil droplets, which attracts a protein to the surface. This protein has a molecular mass of lOkDa and is called colipase. Colipase, also secreted from the pancreas, is essential for the activity of pancreatic lipase, which is otherwise strongly inhibited by bile salts. Thus, bile salts, colipase and pancreatic lipase interact in a ternary complex, which also contains calcium ions that are necessary for the full lipolytic activity.

Lipid Digestion And Absorption
Fig. 5.2 The structure of a bile acid (cholic acid).

Pancreatic lipase catalyses the hydrolysis of fatty acids from positions l and 3 of triacylglycerols to yield 2-monoacylglycerols. There is very little hydrolysis of the ester bond at position 2 and very little isomerization to the l(3)-monoacylglycerols, presumably because of rapid uptake of the mono-acylglycerols into epithelial cells. Phospholipase A2 (Section 7.2.2) hydrolyses the fatty acid at position 2 of phospholipids, the most abundant being phos-phatidylcholine. The enzyme is present as an inactive proenzyme in pancreatic juice and is activated by the tryptic hydrolysis of a heptapeptide from the N-terminus. The major digestion products that accumulate in intestinal contents are lysophos-pholipids. Any cholesteryl ester entering the small intestine is hydrolysed by a pancreatic cholesteryl ester hydrolase.

As these enzymes act upon the contents of the large emulsion particles, which may be around l ^m in diameter, the products of their hydrolytic action disperse and form multimolecular aggregates called mixed micelles (Fig. 5.3), typically 4-6 nm in diameter. Lysophospholipids and monoacylglycerols are highly amphipathic substances and, with bile salts, stabilize these aggregates. In the more neutral environment of the small

Mixed Micelle Water Transport Absorption
Fig. 5.3 Role of the mixed micelle in fat absorption.

intestine, fatty acids are found largely in the ionized form and are therefore also amphipathic. The presence of these amphiphiles helps to incorporate insoluble non-polar molecules like cholesterol and the fat-soluble vitamins into the micelles and aid their absorption.

In ruminant animals, the complex population of micro-organisms contains lipases that split tri-acylglycerols completely to glycerol and non-esterified fatty acids. Some of these are fermented to acetic and propionic acids, which are absorbed directly from the rumen and carried to the liver, where they are substrates for gluconeogenesis. A proportion of the remaining long-chain unsatu-rated fatty acids undergoes several metabolic transformations catalysed by enzymes in the rumen micro-organisms (Fig. 2.22) before passing into the small intestine where they are absorbed. Principal among these is hydrogenation, in which double bonds are reduced by a process that is strictly anaerobic (Section 2.2.6). During hydrogenation, some double bonds are isomerized from the cis to the trans geometrical configuration. Positional iso-merization also occurs, in which the double bonds, both cis and trans, migrate along the carbon chain. The result is a complex mixture of fatty acids, generally less unsaturated than the fatty acids in the ruminant's diet and containing a wide spectrum of positional and geometrical isomers. Because there is very little monoacylglycerol present in the digestion mixture, the mixed micelles in ruminants are composed largely of non-esterified fatty acids, lysophospholipids and bile salts

5.1.2 The intraluminal phase of fat absorption involves passage of digestion products into the absorptive cells of the small intestine

Lipid absorption in humans begins in the distal duodenum and is completed in the jejunum. The principal molecular species passing across the brush-border membrane of the enterocyte are the monoacylglycerols and non-esterified long-chain fatty acids. The bile salts themselves are not absorbed in the proximal small intestine, but pass on to the ileum where they are absorbed and recirculated in the portal blood to the liver, from whence they are re-secreted in the bile. This is also true for some cholesterol that is a constituent of bile. The recirculation of bile constituents in this way is referred to as the entero-hepatic circulation. It may be interrupted by resins (given by mouth) that bind cholesterol and bile salts and prevent their reabsorption, leading the liver to synthesize new bile salts from cholesterol. This is therefore a mechanism for depleting the body of cholesterol and may be useful in the treatment of high cholesterol levels.

The digestion products encounter two main barriers to their absorption. At the surface of the microvillus membrane is a region known as the unstirred water layer. The mixed micelles are small enough to diffuse readily into this layer. It is a few hundred micrometres thick and is retained by mucopolysaccharides secreted by the epithelial cells (mucosa). Its pH is relatively acidic. This will promote the protonation of non-esterified fatty acids (i.e. they become uncharged) so that they can more easily leave the micelles and move into the epithelial cell membrane. This membrane is highly convoluted (hence the description brush-border) to increase its absorptive capacity. There is a suggestion that pancreatic lipase may be loosely bound to the brush-border membrane, which would bring the products of its action even more closely into contact with the absorptive surface.

The second barrier is the brush-border membrane itself. It has been speculated for many years that fatty acids in their protonated form might diffuse across this membrane (and other cell membranes). However, it now looks increasingly likely that there is a specific transport protein to facilitate their movement into the cell. Two candidate proteins have been identified in enterocytes: plasma membrane fatty acid binding protein (FABPpm) and fatty acid translocase (FAT). The former, despite its name, is not related structurally to the family of intracellular fatty acid binding proteins (Section 2.2.1). FAT has been identified with a cell surface receptor CD36, which is a member of the family of scavenger receptors (Section 5.2.4.4). The relative importance of these two proteins in fatty acid uptake by enterocytes is unknown, if indeed they play any role. This is an area of intense interest at present.

5.1.3 The intracellular phase of fat absorption involves recombination of absorbed products in the enterocytes and packaging for export into the circulation

For efficient absorption into the enterocytes to occur, it is essential that an inward diffusion gradient of lipolysis products is maintained. Two cellular events ensure that this occurs. First, the long-chain fatty acids entering the cells bind to a cytosolic fatty acid binding protein (FABPc). There are two FABPc expressed in enterocytes. One is found only in the intestine and is called I-FABPc (also known as FABP2); the other is known as liver FABP (L-FABPc) and is also expressed in liver and kidney. They are small proteins (molecular mass 14-15 kDa) and bind one or two fatty acids, respectively. The FABPc are believed to play a role in targeting fatty acids within the cell, and also in protecting the cell from the potentially cytotoxic effects of high fatty acid concentrations. They also provide the concentration gradient that ensures efficient fatty acid uptake from the intestinal lumen. It is not clear whether the two FABPc isoforms have different roles, although it has been suggested that I-FABPc is involved in the uptake of dietary fatty acids for triacylglycerol synthesis, whilst L-FABPc in enterocytes is involved in uptake of fatty acids delivered in the blood, which may be substrates for oxidation and for phospholipid synthesis. Both these FABPc bind long-chain unsaturated fatty acids with higher affinity than saturated fatty acids, and this may explain the more rapid absorption of oleic than stearic acid.

Up to this stage, the absorption process has not been dependent on a source of energy. The next phase, which removes fatty acids, thereby maintaining a gradient, is the energy-dependent re-esterification of the absorbed fatty acids into tri-acylglycerols and phospholipids. The first step in re-esterification is the ATP-dependent 'activation' of fatty acids to their acyl-CoA thioesters (Section

2.2.1). Again, the preferred substrates are the long-chain fatty acids. There are several isoforms of acyl-CoA synthetase (ACS), one of which, ACS5, is prominent in the intestine. The ACSs are all membrane-associated and are situated on the endo-plasmic reticulum as well as on mitochondrial and peroxisomal membranes. The acyl-CoA thioesters are themselves bound by a specific, 10 kDa, cyto-solic acyl-CoA binding protein which, like FABPc, may direct the acyl-CoA within the cell.

In humans and other simple-stomached animals, the major acceptors for esterification of acyl-CoA are the 2-monoacylglycerols that together with the non-esterified fatty acids are the major forms of absorbed lipids. Resynthesis of triacylglycerols, therefore, occurs mainly via the monoacylglycerol pathway (Section 3.4.2). In ruminant animals, the major absorbed products of lipid digestion are glycerol and non-esterified fatty acids and resynthesis occurs via the glycerol phosphate pathway (Section 3.4.1.1) after phosphorylation of glycerol catalysed by glycerol kinase. It should be noted, however, that lipids usually form a minor part of ruminant diets, so that glucose is probably the major precursor of glycerol phosphate in the ruminant enterocyte.

The main absorbed product of phospholipid digestion is monoacylphosphatidylcholine (lyso-phosphatidylcholine). A fatty acid is re-esterified to position 1 to form phosphatidylcholine by an acyl transferase located in the villus tips of the intestinal brush-border. The function of this phospholipid will be to stabilize the triacylglycerol-rich particles (chylomicrons) exported from the cell as described later. It is thought that the phosphatidylcholine used for the synthesis and repair of membranes in the enterocytes (cells with a rapid turnover) is synthesized by the classical CDP-choline pathway (Section 7.1.5) in cells at the villus crypts.

The absorption of cholesterol is slower and less complete than that of the other lipids, about half of the absorbed sterol being lost during desquamation of cells. Most of the absorbed portion is esterified either by reversal of cholesteryl esterase or via acyl-CoA:cholesterol acyltransferase (Section 7.5.6). The latter enzyme is induced by high concentrations of dietary cholesterol.

During fat absorption, the biosynthetic activity of the enterocyte is geared to packaging the resyn-thesized absorbed lipids in a form that is stabilized for transport in the aqueous environment of the blood. Within minutes of absorption products entering the enterocyte, fat droplets can be seen within the cysternae of the smooth endoplasmic reticulum, where the enzymes of the mono-acylglycerol pathway are located. The rough endoplasmic reticulum is the site of the synthesis of phospholipids (Section 7.1) and apolipoproteins (Section 5.2.2), which provide the coat that stabilizes the lipid droplets. One apolipoprotein in particular, apolipoprotein B48 (apoB48), provides a 'skeleton' which associates with lipid during its synthesis, forming the immature chylomicron particle. These immature particles gain further tri-acylglycerol in a process that involves the microsomal triacylglycerol transfer protein (MTP). They migrate through the Golgi apparatus where carbohydrate moieties are added to the apolipo-proteins, and the fully formed chylomicrons are exported in secretory vesicles that move to the basolateral surface of the enterocyte. The final phase of transport from the cells involves fusion with the membrane and secretion into the intercellular space by exocytosis (Fig. 5.1). Chylomicron assembly in the enterocyte is similar to the assembly of very low density lipoprotein (VLDL) particles in hepatocytes (Section 5.2.3). The process is illustrated in Fig. 5.4.

The chylomicrons do not enter the plasma directly. Instead they are secreted into the tiny lymph vessels that are found inside each of the intestinal villi, called lacteals because of their milky appearance after the ingestion of fat. From here the chylomicrons pass via the thoracic duct (a main branch of the lymphatic system) and enter the circulation in the subclavian vein, from where they reach the heart for distribution around the body. Thus, dietary lipids, contained in the chylomicrons, are unique amongst the products of intestinal digestion and absorption in that they do not enter the hepatic portal vein and traverse the liver before entering the systemic circulation.

Chylomicrons are the main route for the transport of dietary long-chain fatty acids. Those with chain lengths of less than twelve carbon atoms are absorbed in the non-esterified form, passing directly into the portal blood and are metabolized directly by P-oxidation in the liver. There are several reasons for this partition. Firstly, short- and medium-chain fatty acids are more readily hydro-lysed from triacylglycerols and since they occupy mainly position 3, are not retained in the 2-mono-acylglycerols. Secondly, they are more likely to diffuse into the aqueous phase rather than the mixed micelles and for this reason are more rapidly absorbed. Around 4gday_1 short- and medium-chain fatty acids enter the diet from dairy products or foods that incorporate coconut or palm kernel oils. Short-chain fatty acids derived by microbial fermentation of non-starch polysaccharides (dietary fibre) in the colon are also absorbed and contribute to lipid metabolism.

5.1.4 Malassimilation of lipids, through failure to digest or absorb lipids properly, can arise from defects in the gut or other tissues but may also be induced deliberately

Failure to assimilate lipids of dietary origin into the body may arise from defects in digestion (maldigestion) or absorption (malabsorption).

Maldigestion can occur because of incomplete lipolysis. Thus, pancreatic insufficiency, which may result from pancreatitis, pancreatic tumour, diseases of malnutrition such as kwashiorkor, or rarely from an inherited mutation in pancreatic lipase, can lead to a failure to secrete enough lipase or the production of an enzyme with reduced or no activity. Alternatively, the lipase may be fully functional but a failure to produce bile (generally arising from hepatic insufficiency) may result in an inability to effect the micellar solubilization of lipolysis products. This, in turn, feeds back to cause an inhibition of lipolysis. Gastric disturbances that result in abnormal acid secretion also inhibit pancreatic lipase and, furthermore, gastric problems may cause poor initial emulsifi-cation of the lipid in the stomach, further reducing the efficiency of digestion. Thus, maldigestion can arise from defects in a variety of organs con apoB mRNA

Enterocyte Phytosterols

Fig. 5.4 Assembly of triacylglycerol-rich lipoprotein particles, chylomicrons in the enterocyte, and VLDL in the hepatocyte. Apolipoprotein B48 (apoBlOO in hepatocytes) is synthesized on the rough endoplasmic reticulum (ER) (upper left). At step 4, the N-terminal region acquires a small amount of 'core lipid' (triacylglycerols and cholesteryl esters) in a process mediated by the microsomal triacylglycerol transfer protein (MTP). After further protein chain synthesis (step 5), a lipid-poor 'primordial' particle is produced. There is debate about whether this is released into the ER lumen as shown at step 6, or whether the next stage, of bulk lipid addition (step 7), occurs whilst the primordial particle is still attached to the ER membrane. There is also debate about whether MTP is involved in this stage also (consensus is that it probably is). The left side of the diagram indicates that if lipid availability is low and lipid addition fails to occur, then the nascent apoB is directed into a degradative pathway (steps 9 and lO). Reproduced, with permission of the Nutrition Society, from White, D.A., Bennett, A.J., Billett, M.A. & Salter, A.M. (1998) The assembly of triacylglycerol-rich lipoproteins: an essential role for the microsomal triacylglycerol transfer protein. British journal of Nutrition, 80, 219-229.

Fig. 5.4 Assembly of triacylglycerol-rich lipoprotein particles, chylomicrons in the enterocyte, and VLDL in the hepatocyte. Apolipoprotein B48 (apoBlOO in hepatocytes) is synthesized on the rough endoplasmic reticulum (ER) (upper left). At step 4, the N-terminal region acquires a small amount of 'core lipid' (triacylglycerols and cholesteryl esters) in a process mediated by the microsomal triacylglycerol transfer protein (MTP). After further protein chain synthesis (step 5), a lipid-poor 'primordial' particle is produced. There is debate about whether this is released into the ER lumen as shown at step 6, or whether the next stage, of bulk lipid addition (step 7), occurs whilst the primordial particle is still attached to the ER membrane. There is also debate about whether MTP is involved in this stage also (consensus is that it probably is). The left side of the diagram indicates that if lipid availability is low and lipid addition fails to occur, then the nascent apoB is directed into a degradative pathway (steps 9 and lO). Reproduced, with permission of the Nutrition Society, from White, D.A., Bennett, A.J., Billett, M.A. & Salter, A.M. (1998) The assembly of triacylglycerol-rich lipoproteins: an essential role for the microsomal triacylglycerol transfer protein. British journal of Nutrition, 80, 219-229.

tributing to different aspects of the digestive process.

Malabsorption may occur, even when digestion is functioning normally, due to defects in the small intestine affecting the absorptive surfaces. There may be a variety of causes, some common ones being bacterial invasion of the gut or sensitization of the gut to dietary components such as gluten, as in coeliac disease. Malabsorption syndromes (often called sprue) are characterized by dramatic changes in the morphology of the intestinal mucosa. The epithelium is flattened and irregular and atrophy of the villi reduces the absorbing surface. Tropical sprue is a prevalent disease in many countries of Africa and Asia. Malabsorption of fat can also occur in certain inherited disorders in which the formation of chylomicrons is impaired, so that fat cannot be transported out of the cell. Triacylglycerols then accumulate in the enterocyte. One such condition is known as chylomicron retention disease or Anderson's disease. The molecular defect is not known.

Digestion and absorption may also be interfered with deliberately to reduce fat absorption in an attempt to control body weight. Synthetic fat substitutes, in particular sucrose-polyesters (sucrose with long-chain fatty acids esterified to its hydroxyl groups; Section 4.1.3.6), can be used in cooking, and are completely resistant to the action of pancreatic lipase. They are used at present in some snack foods that might otherwise contribute significantly to energy intake. Similarly, a bacterial metabolite known as tetrahydrolipstatin (or orlistat) is licensed for prescription as a drug to treat obesity. Tetra-hydrolipstatin is a potent irreversible inhibitor of pancreatic lipase and so reduces the absorption of dietary fat. Certain plant sterols (phytosterols) can interfere with the absorption of cholesterol of both dietary and biliary origin, and are being marketed as components of spreads that can help to lower cholesterol levels in the blood.

A common feature of all fat malassimilation syndromes is increased excretion of fat in the faeces (steatorrhoea), which arises not only from unab-sorbed dietary material but also from the bacterial population that usually proliferates in the gut and the breakdown of cells. The bacteria undoubtedly affect the composition of the excreted fat. For example, a major component (absent from the diet) of faecal fat, 10-hydroxystearic acid, was shown by tracer studies to be formed by bacteria from stearic acid. This is a normal component but found in particularly high concentration in patients with steatorrhoea.

Patients with poor fat absorption are very much at risk from deficiencies of energy, fat-soluble vitamins and of essential fatty acids (Section 4.2). The clinical management of fat malassimilation is facilitated, according to the nature of the defect, by giving bile salts in tablet form or a pancreatic extract containing pancreatic lipase and other enzymes, or by replacing normal dietary fats by medium-chain triacylglycerols (MCT). This product is composed largely of triacylglycerols with C8 and C10 saturated fatty acids refined from coconut oil, and can be purchased as a cooking oil or as a fat spread. The medium-chain fatty acids are rapidly hydrolysed and efficiently absorbed into the portal blood, thereby bypassing the normal absorptive route of long-chain fatty acids and chylomicron formation.

Some people are unable to take any nutrition by mouth, usually because of inflammatory conditions of the bowel or infection following surgical intervention. In early attempts at complete nutrition of such people using the intravenous route, their energy requirements were supplied in the form of glucose and amino acids. Several such patients developed symptoms of essential fatty acid deficiency (Section 4.2.3.1). In addition, the large carbohydrate loads caused metabolic problems, not least because such patients often have a reduced ability to handle glucose, associated with their inflammatory condition. In the early 1960s Arvid Wretlind in Sweden developed the first synthetic lipid emulsion that could be infused intravenously. It was based on an emulsion of soybean oil stabilized with lecithin, and was soon available commercially. Now there is a number of such intravenous lipid preparations with different combinations of fatty acids, including some enriched with the very long-chain polyenoic fatty acids 20:5n-3 and 22:6n-3.

5.2 TRANSPORT OF LIPIDS IN THE BLOOD: PLASMA LIPOPROTEINS

Lipids, being insoluble in water, need to be combined with proteins for transport in the blood. These plasma lipoproteins represent a continuum of lipid-protein complexes in which the ratio of lipid to protein, and hence their density, varies.

5.2.1 Lipoproteins can be conveniently divided into groups according to density

The biological problem of how to transport water-immiscible lipids in the predominantly aqueous environment of the blood has been solved by emulsification. Aggregates of hydrophobic molecules (particularly triacylglycerol and cholesteryl esters) are stabilized with a coat of amphipathic compounds: phospholipids, unesterified cholesterol and proteins. The resulting particles are the lipoproteins. The protein moieties are known as apolipoproteins and, as will be discussed later, have more than a stabilizing role. They also confer specificity on the particles, allowing them to be recognized by specific receptors on cell surfaces, and they regulate the activity of some enzymes involved in lipoprotein metabolism.

The lipoprotein system developed quite early in evolution. Birds, fishes, amphibians and even roundworms have a system for delivery of lipids from lipogenic organs to the developing egg that is closely related to the mammalian lipid transport system, and some of the proteins involved are homologous. For instance, the protein involved in lipid transport in these various groups is known as vitellogenin and is related to mammalian apolipoprotein B. The vitellogenin receptor of the chicken oocyte will, in fact, recognize mammalian apolipoprotein B, suggesting a common origin with mammalian lipopro-tein receptors (Section 5.2.4). The mammalian lipase gene family (pancreatic, lipoprotein, hepatic and endothelial lipases; Section 3.5.2) is homologous to proteins in egg yolk of Drosophila that are presumably involved in related functions.

There are several types of lipoproteins with differing chemical compositions, physical properties and metabolic functions (Table 5.1), but their common role is to transport lipids from one tissue to another, to supply the lipid needs of different cells. The different lipoproteins may be classified in a number of ways depending on their origins, their major functions, their composition, physical properties or method of isolation. They differ according to the ratio of lipid to protein within the particle as well as in the proportions of lipids (triacylglycerols, esterified and non-esterified cholesterol and phos-pholipids). These compositional differences influence the density of the particles: in general, the higher the lipid to protein ratio, the larger the particle and the lower its density. There is a strong relationship between biological function and the density class into which a particle falls. It is convenient, therefore, to make use of density to separate and isolate lipoproteins by ultracentrifugation, and it is now usual to classify plasma lipoproteins into different density classes. It is almost by good fortune for the lipid biochemist that this classification is also, at least approximately, one of function. From lowest to highest density, these are: chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins (HDL). (An additional class of intermediate density lipoproteins, IDL, is sometimes included between VLDL and LDL.) As density increases, so the ratio of triacylglycerols to phos-pholipids and cholesterol decreases (Table 5.1): chylomicrons and VLDL particles are often grouped as the triacylglycerol-rich lipoproteins, whereas LDL and HDL are more important as carriers of cholesterol.

It is important to emphasize that the classes are

Table 5.1 Composition and characteristics of the human plasma lipoproteins
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Responses

  • birikti
    How are lipids digested and absorbed in the body?
    5 years ago
  • Romola
    How micelles transport fats?
    5 years ago
  • ATTE
    How lipids,carbohydrates and proteins are digested and absorbed?
    5 years ago
  • VALDEMAR
    How absorption takes place in the small intestine?
    5 years ago
  • Allie
    Why role of fat can pass through absorption digestion?
    5 years ago
  • amy
    How are the components of fats absorbed in the small intestine?
    5 years ago
  • pervinca
    Why are MCT preffered in steatorrhoea?
    4 years ago
  • kieron
    What components of the pancreatic juice are needed for efficient lipid digestion?
    4 years ago
  • MARCEL
    Which fatty acids are absorbed by the gastrointestinal better?
    4 years ago
  • felix lange
    What is the assembly of materials for absorption of lipid?
    9 months ago
  • NOORA
    What are micelles and mixed micelles in fat absorption?
    9 months ago
  • Larry
    How lipid is absorb biochemical?
    8 months ago
  • marko moeller
    How are intravenous lipids absorbed and digested the body?
    5 months ago
  • mariano
    What would defective digestion and absorption of fat lead to?
    4 months ago
  • gabriele
    How lipids are digested and absorbed in ruminant diet?
    3 days ago

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