Download Intestinal Digestion and Absorption of Sugars

Abstracts of Communications
554th Meeting of the Biochemical Society
Queen Elizabeth College, London
24 and 25 March 7975
CARBOHYDRATE INTOLERANCE: a Colloquium
organized on behalf of the Society and the Carbohydrate
Biochemistry Group by D. Robinson (London)
Intestinal Digestion and Absorption of Sugars
GIORGIO SEMENZA
Laboratoriurn f i r Biochernie der ETH-Zurich, Zurich, Switzerland
Monosaccharides
Glucalogues (i.e. sugars of the D - ~ ~ U C Otype)
S ~ are absorbed at the mucosal surface of
hamster small intestine by at least two sodium-dependent transport systems (Honegger
& Semenza, 1973; Honegger & Gershon, 1974). In fact, (i) the concentration-dependence
of unidirectional flux of both glucose and D-galactose is described by two, rather than
one, horizontal hyperbolae; (ii) mutual inhibition by monosaccharides can only be
described satisfactorilyby assuming at least two carrier systems of partially overlapping
specificity;(iii) the two carrier systems show different distributionsalong the small intestine; and (iv) the ratio between the maximum unidirectional fluxes of the two systems
changes during the first weeks of extrauterine life. The latter observation, if valid in the
human also, may provide an explanation for the apparent, if partial, recovery in patients
affected by glucose-galactose malabsorption (Meeuwisse, 1970).
Vesicles from intestinal brush-border membranes have proved of considerable value
in establishing D-glucose uptake across these membranes as being coupled to the Na+
electrochemical gradient across the membrane, rather than to other forms of metabolic
energy (Hopfer et al., 1973; Murer & Hopfer, 1974). In a new preparation of vesicles
from brush-border membranes (which have a lower sodium permeability) higher transient accumulation of D - ~ ~ U C Ointo
S ~ the intravesicular space could be observed in the
presence of a suitable sodium gradient (C. Storelli, M. Kessler, M. Muller & G. Semenza,
unpublished work). All observations are adequately described and predicted by
Crane’s (1962,1965) co-transport hypothesis for D-glucose transport at the brush border
of the enterocytes.
D-Fructose is transported apparently by a single (Honegger & Semenza, 1973),
sodium-independent saturable system (Honegger & Semenza, 1973 ; Sigrist-Nelson &
Hopfer, 1974, and references therein).
Fructose uptake which is not stimulated by Na+, does not lead to accumulation against
concentration gradient (Sigrist-Nelson & Hopfer, 1974). In agreement with Crane’s
(1962, 1965) hypothesis, D-glucose transport across the lateral-basal membranes of
enterocytes is sodium independent (Bihler & Cybulsky, 1973; Murer et al., 1974; H.
Sigrist, E. Ammann & H. Murer, unpublished work), and does not produce accumulation against a concentration gradient.
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BIOCHEMICAL SOCIETY TRANSACTIONS
Disaccharides
Oligo- and di-saccharideswhich cannot be hydrolysed are absorbed in trace amounts,
if at all. Thus sucrose in sucrase-isomaltase deficiency and lactose in lactase deficiency,
trehalose in trehalase deficiency, if present in intestinal lumen in sufficient amounts,
produce water movements which can lead to diarrhoea.
The brush-border membrane of the ‘average mammal’ is endowed with a number of
oligo- and di-saccharidases [for reviews, see Semenza (1968) and Dahlqvist (1965)],
one (or two) maltase-glucoamylase(s), one maltase-sucrase, one maltase-isomaltase,
one trehalase, one lactase, and onemajor ‘phlorrhizinhydrolase’ (Malathi &Crane, 1969)
[(and one minor additional phlorrhizin hydrolase (Kraml et al., 1972)l. Sucrase and isomaltase have a molecular weight of approx. 110000 each, are glycoproteins(Cogoli et al.,
1973) belonging to the same ABO blood group as the erythrocytes of the same individual
(Kelly & Alpers, 1973); have similar catalytic and other properties, and are bound
together in a di-enzyme complex (Cogoli et al., 1973). They are subjected to the same or
to related biological control mechanism(s), as shown by the constancy of the
sucrase/isomaltase ratio in random samples of human biopsies (Auricchio et al., 1963),
their simultaneous appearance during development (Rubino et al., 1964; Dahlqvist
& Lindberg, 1966) and absence from (Preiser et al., 1974; J. Schmitz, C. Commegrain,
D. Maestracci & J. Rey, unpublished work) or lack of activity (Dubs et al., 1973, 1975)
in the brush-border membrane of sucrase-isomaltase maldigestors.
The major phlorrhizin hydrolase of small intestinal brush borders has been identified (in rat) with Brady’s (Brady et al., 1965) glycosyl ceramidase (Leese &
Semenza, 1973). It is associated with lactase (the ‘8-glycosidase complex’) and is subjected to the same or to similar biological control mechnnism(s) as lactase. The physical
and biological association of glycosylceramidase and lactase may be of physiological
significance [for a review, see Semenza et al. (1975a)l.
The hydrolytic mechanism of sucrase and isomaltase includes the protonation of the
glycosidic oxygen, splitting of the bond between glucosyl Ci and glycosidic oxygen,
formation of a carbonium ion which is temporarily stabilized by a carboxylate of the
active site, and Gnally by a OH- from the water, with the return of the a configurationat
C1 (Quaroni et al., 1974; Stefani et al., 1975; Cogoli & Semenza, 1975; Semenza et al.,
19756).
Most of the monosaccharides liberated by the action of membrane-bound disaccharidases are efficiently picked up by the transport systems for monosaccharides
(Miller &Crane, 1961 ;Parsons & Prichard, 1971 ;Hamilton & McMichael, 1968). However, it was established by Crane’s group (Malathi et al., 1973; Ramaswamy et al.,
1974) that some of the sugars that are provided as disaccharides enter by other route(s).
These transport system(s) are (i) not (as) accessible to free monosaccharides, (ii) slightly
or not sodium dependent, (iii) less sensitive to phlorrhizin and (iv) slightly or not
inhibited by Tris, in spite of the corresponding hydrolytic activities being strongly
inhibited by it (Crane et al., 1970; Malathi et al., 1973; Ramaswamy et al., 1974).
Although these transport systems are probably of little physiological significance (not
more than 5-10% of the monosaccharides arising from disaccharides seem to utilize this
route; Ramaswamy eta/.,1974), they areofconsiderable theoretical interest, because they
have provided the first example of a natural transport system to be reconstituted in artificial membranes [in BLM (black lipid membranes) (Storelli et al., 1972) and in liposomes (Semenza et al., 19756)] from a homogeneous membrane protein: the sucraseisomaltase complex was solubilized by papain digestion, obtained in homogeneous form
and incorporated into lipids. The BLM obtained therefrom had a permeability coefficient
for 14C-labelled sucrose (or, rather, for the monosaccharides arising from it) which was
larger than that for protein-free BLM by some three orders of magnitude, at least. The
permeability to mannitol, D-glucose or D-fructose was little affected by the sucraseisomaltase complex, if at all.
More recently we reconstituted the same transport system, using Triton-solubilized
the sucrase-isomaltase complex and monolamellar liposomes (Semenza et al., 19756).
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The reconstituted systems had the same characteristics as the original one. The
observations available up to now restrict the choice of the possible mechanisms of the
sucrase-dependent sugar-transport system to two. (i) If the hydrolysis is efficiently
vectorial, a local hyperconcentration of glucose and fructose may arise which could
provide a concentration ‘head’ for an apparently increased ‘passive’ diffusion across the
lipid bilayer. (ii) The active site of sucrase may have access, either all the time or alternatively, to both sides of the lipid membrane (Semenza et al., 19756).
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Clinical Studies of Carbohydrate Digestion and Absorption
HUGH B. McMICHAEL
King Edward Memorial Hospital, London W13 9NU, U.K.
Since stool water isessentially iso-osmotic (Wilson etal., 1968),the presence in the rectum
of as little as 3 g of lactic acid derived from unabsorbed carbohydratemay cause diarrhoea
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