Brush border

The first member of this class, acarbose, was introduced in the early 1990s. a-Glucosidase inhibitors slow the intestinal process of carbohydrate digestion by competitive inhibition of the activity of a-glucosidase enzymes located in the brush border of the enterocytes... 

Sodium-dependent glucose cotransporters (SGLT) are located on small-intestine and kidney brush-border membranes. SGLT1, SGLT2, and SGLT3 are... 

In eukaryotes there is also evidence that Met(O) is actively transported. It has been reported that Met(O) is transported into purified rabbit intestinal and renal brush border membrane vesicles by a Met-dependent mechanism and accumulates inside the vesicles against a concentration gradient102. In both types of vesicles the rate of transport is increased with increasing concentrations of Na+ in the incubation medium. The effect of the Na+ is to increase the affinity of Met(O) for the carrier. Similar to that found in the bacterial system, the presence of Met and other amino acids in the incubation medium decreased the transport of Met(O). These results suggest that Met(O) is not transported by a unique carrier. 

Mooseker, M.S. (1985). Organization, chemistry, and assembly of the cytoskeletal apparatus of the intestinal brush border. Ann. Rev. Cell Biol. 1, 209-241. 

Myosin-I molecules have several IQ sequences on or near the head and have light chains associated with them (Cheney and Mooseker, 1992 Cheney et al., 1993). Frequently, the light chains appear to be calmodulin molecules and some myosin-I molecules can bind three to four molecules of calmodulin at one time. Brush-border and adrenal myosin-I also bind calmodulin. Acanthamoeba myosin-I has a light chain that can be removed, in vitro, without adversely affecting the ATPase activity or the heavy chain phosphorylation (Korn and Hammer, 1988). The role of these calmodulin molecules in regulating myosin-I is complex and poorly understood. One possibility is that the calmodulin molecules dissociate from the heavy chains when calcium binds to the calmodulin, thereby imparting greater flexibility to the head of the myosin-I molecules. 

Wali RK, Singh R, Dudeja PK, et al. 1982. Effect of a single oral dose of endosulfan on intestinal uptake of nutrients and on brush-border enzymes in rats. Toxicol Lett 12 7-12. 

There are two main classes of proteolytic digestive enzymes (proteases), with different specificities for the amino acids forming the peptide bond to be hydrolyzed. Endopeptidases hydrolyze peptide bonds between specific amino acids throughout the molecule. They are the first enzymes to act, yielding a larger number of smaller fragments, eg, pepsin in the gastric juice and trypsin, chymotrypsin, and elastase secreted into the small intestine by the pancreas. Exopeptidases catalyze the hydrolysis of peptide bonds, one at a time, fi"om the ends of polypeptides. Carboxypeptidases, secreted in the pancreatic juice, release amino acids from rhe free carboxyl terminal, and aminopeptidases, secreted by the intestinal mucosal cells, release amino acids from the amino terminal. Dipeptides, which are not substrates for exopeptidases, are hydrolyzed in the brush border of intestinal mucosal cells by dipeptidases. 

As might be expected, mRNA for the 5-HT transporter is found in high concentrations in the Raphe nuclei but it is also found in other brain regions. Whether this means that non-5-HT neurons can synthesise this protein is unknown but there is some evidence that it is synthesised in astrocytes, at least. One complication is that there are multiple forms of mRNA for the 5-HT transporter, but there is, as yet, no evidence for transporter subtypes in the CNS. However, it must also be remembered that 5-HT transporters are found in the peripheral tissues, notably platelets, mast cells, the placental brush-border and adrenal chromaffin cells and it is possible that these are not all identical. 

Irrespective of the physical form of the carotenoid in the plant tissue it needs to be dissolved directly into the bulk lipid phase (emulsion) and then into the mixed micelles formed from the emulsion droplets by the action of lipases and bile. Alternatively it can dissolve directly into the mixed micelles. The micelles then diffuse through the unstirred water layer covering the brush border of the enterocytes and dissociate, and the components are then absorbed. Although lipid absorption at this point is essentially complete, bile salts and sterols (cholesterol) may not be fully absorbed and are not wholly recovered more distally, some being lost into the large intestine. It is not known whether carotenoids incorporated into mixed micelles are fully or only partially absorbed. 

The complex polymers in feedstuffs are broken down to the constituent building blocks by a sequential process. Hydrolysis of the polymers is initiated in the lumen of the GIT by enzymes and other secretions produced by the pancreas, stomach, intestine, liver and gall bladder, and other GIT tissues, and completed by another suite of enzymes associated with the brush border membrane (BBM) or intracellular organelles. Anti-nutrient phytochemicals can decrease the hydrolysis of feedstuffs, and thereby reduce nutrient availability, either by increasing the inherent resistance of the polymers to hydrolysis or by decreasing the activities or amounts of enzymes and other secretions produced by the GIT. 

Potential enzymes involved in anthocyanin metabolism — The lactase phlorizin hydrolase (LPH EC 3.2.1.108) present only in the small intestine on the outside of the brush border membrane and the cytosolic P-glucosidase (CBG EC 3.2.1.1) found in many tissues, particularly in liver, can catalyze the deglycosylation (or hydrolysis) of polyphenols. LPH may play a major role in polyphenol metabolism... 

Biochemical studies of plasma membrane Na /H exchangers have been directed at two major goals (1) identification of amino acids that are involved in the transport mechanism and (2) identification and characterization of the transport pro-tein(s). To date, most studies have been performed on the amiloride-resistant form of Na /H" exchanger that is present in apical or brush border membrane vesicles from mammalian kidney, probably because of the relative abundance of transport activity in this starting material. However, some studies have also been performed on the amiloride-sensitive isoform present in non-epithelial cells. 

Kinetic studies indicated that external H interacted with the renal brush border Na /H exchanger (resistant-type) at a single site with apparent pKa 7.3-7.5. Because the imidazolium ring of histidine is the principal group that is titratable in this... 

Renal brush border DEPC, Rose bengal I aVme,.) Amiloride 17... 

Renal brush border DCCD,EEDQ Amilioride, 20-24... 

Ganapathy et al. [18] showed that the human placental brush border Na" /H exchanger (a sensitive-type) was also inactivated by DEPC, and amiloride protected against inhibition. DEPC also inactivated the sensitive-type Na /H exchanger in thymic lymphocytes [19]. 

Further evidence that carboxyl groups are important for transport activity was provided by Igarashi and Aronson [22], Friedrich et al. [23], and Kinsella et al. [24] using the carboxyl group-specific reagent, A,A -dicyclohexylcarbodiimide (DCCD). DCCD irreversibly inactivated the brush border Na /H exchanger in rabbit and... 

Na oi and was partially blocked by amiloride but not by cimetidine. Since these investigators also found that amiloride and cimetidine bound competitively with Na" at the external transport site of the placental brush border Na /H exchanger, they concluded that the vicinal dithiol groups are necessary for transport function but are located at a site distinct from the external transport site. 

Igarashi and Aronson [22] found that the renal brush border Na /H exchanger (resistant-type) was inhibited 40% by 1 mM NEM, and inhibition was not blocked by 1 mM amiloride. Haggerty et al. [13] reported that both the apical and basolat-eral Na /H exchangers in LLC-PKi cells were inactivated by 0.5mM NEM, although the apical Na /H exchanger was more sensitive to inhibition (70% inhibition compared to 20% inhibition of the basolateral transport activity). 

---