Absorption from the small intestine 331 Monosaccharides

The hydrolysis of the digestible carbohydrates proceeds to the stage of mon-osaccharides, some of which are liberated by the enzymes of the brush border membrane. These must then enter the enterocytes, the absorptive cells of the intestinal mucosa. Mechanisms by which sugars cross cell membranes were summarised in Box 2.2. The role of the various monosaccharide transporters in carbohydrate absorption is summarised in Fig. 3.7. Glucose and galactose enter by active transport mediated by the sodium-glucose cotransporter SGLT-1; i.e. these sugar molecules may be absorbed against a concentration gradient (see Box 2.1). During the active phase of digestion, it is likely that the local concentration of free glucose or galactose on the luminal surface of the brush border membrane is so high that this is unnecessary, but during the early and late phases of digestion active transport ensures complete capture of almost all the intestinal sugar molecules. Energy is provided by a concentration gradient

Box 3.1 The bile acids and salts

These are derivatives of cholesterol (see Fig. 1.6), synthesised in the liver. A typical bile acid is shown. This is cholic acid. Chenodeoxycholic acid lacks the hydroxyl group at carbon 12. They are secreted in the bile in the form of cova-lent conjugates, formed with a base: either glycine as shown here, or taurine (+H3NCH2CH2SO3-). The conjugate shown is sometimes known as glycocho-late. They are amphipathic molecules, with a predominantly non-polar ring structure but a highly polar acidic group (especially in the conjugated form).

The first committed step in bile acid synthesis from cholesterol is hydroxyla-tion of carbon 7 (marked on figure). This is brought about by an enzyme formerly known as cholesterol 7-a hydroxylase. This enzyme, like many involved in hydroxylation reactions, is a member of a large family of haem proteins that has the characteristic (when it has bound CO) of absorbing light at a wavelength of 450 nm, known generally as cytochrome P-450. Because of this, it now has the 'family name' CYP7A1. CYP7A1 expression is controlled primarily at the transcriptional level by the relative levels of cholesterol and bile acids in the hepatocyte, through a nuclear receptor/transcription factor known as LXR (liver X-receptor).

Bile acid (cholate)

Conjugate base (Glycine)

The bile salts are not absorbed with the contents of the mixed micelles. Instead, they are absorbed from the terminal part of the ileum by an energy-requiring process. They then enter the portal vein and are re-utilised in the liver. This 'salvaging' of the bile acids is known as the enterohepatic circulation. Bile salts returning to the liver repress the conversion of further cholesterol to bile acids via LXR as described above.

If the reabsorption of bile salts is interrupted, they are excreted, after some bacterial modification, in the faeces. The consequence is that CYP7A1 expression is up-regulated and more cholesterol is converted to bile acids in the liver, depleting the body's cholesterol pool. The usefulness of this as a treatment for lowering of the serum cholesterol concentration will be discussed further in Chapter 9 (Box 9.4).

Fig. 3.6 Lipid digestion and absorption in the small intestine. Fatty acids probably enter the mucosal cells by facilitated diffusion (see Section 2.2.1.3). Within the mucosal cells, 2-monoacylglycerol and fatty acids are re-esterified largely by the monoacylglycerol pathway (see Fig. 3.8, later) and packaged into chylomicrons. Cholesterol absorption is not shown for simplicity; it is described in the text of this chapter and also in Section 2.2.1.4.

Fig. 3.6 Lipid digestion and absorption in the small intestine. Fatty acids probably enter the mucosal cells by facilitated diffusion (see Section 2.2.1.3). Within the mucosal cells, 2-monoacylglycerol and fatty acids are re-esterified largely by the monoacylglycerol pathway (see Fig. 3.8, later) and packaged into chylomicrons. Cholesterol absorption is not shown for simplicity; it is described in the text of this chapter and also in Section 2.2.1.4.

Fig. 3.7 Absorption of monosaccharides from the intestine. Monosaccharides enter the enterocytes across the brush border or apical membrane and leave the cell by the ba-solateral membrane using specific transporter proteins. Based on Thorens (1993); Wright (1993).

of sodium ions across the membrane, maintained in turn by the Na+-K+-ATPase (Fig. 3.7). Fructose, in contrast, is taken up into the mucosal cells by facilitated diffusion by the fructose transporter GLUT5.

The expression of these transporters is regulated by the availability of dietary carbohydrate. SGLT-1 expression is increased by glucose availability in the small intestinal lumen (see Table 2.6). Fructose availability is a specific signal increasing expression of GLUT5.

From within the mucosal cells, the sugars enter the capillaries that form a dense network within each villus (see Fig. 3.3). They must first cross the cell membrane at the 'back end' of the cell - the basolateral membrane (Fig. 3.7), to enter first the interstitial space and then the blood in the vessels draining the small intestine towards the portal vein. This basolateral transport is by facilitated diffusion mediated by GLUT2, which will transport both glucose and fructose. Active transport of sugar into the cell from the intestinal lumen must raise its intracellular concentration to the extent that it will move out, into the interstitial space, down a concentration gradient. Thus, carbohydrate from the diet appears ultimately in the form of monosaccharides in the blood in the hepatic portal vein.

However, not all of the sugars absorbed are liberated into the bloodstream in this way. Some are metabolised by the cells of the intestinal mucosa, which require a constant supply of ATP for maintenance of the sodium gradient. At least a proportion of the glucose used by these cells for ATP generation is metabolised to lactate, again released into the portal vein. The amount of absorbed carbohydrate which is converted to lactate in this way is presently unknown (and very difficult to estimate). The relevance of this pathway of lactate production will be considered again in Section 4.1.2.1.

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