ABSORPTION OF CARBOHYDRATES H.
Newey
ABSORPTION OF CARBOHYDRATES
H. NEWEY PhJX
Medical Research Council
Research Group on Intestinal Absorption
Department of Physiology
University of Sheffield
Digestion and absorption at the macroscopic level
a Disappearance from the lumen
b Appearance in the blood stream
Digestion at the cellular level
Absorption at the cellular level
a Characteristics of the transport process
b Cellular location of the transport process
c Mechanism of monosaccharide transport
References
The process of absorption, including the final stages of diges-
tion, can be conveniently examined at two levels: (0 at the
whole-organ, or macroscopic, level; (ii) at the cellular leveL
Study at the macroscopic level is concerned with activities in
different regions of the gut in order to determine the site of
digestion and absorption; at the cellular level the emphasis is
on what happens in the epithelial cell, and how its activities
are involved in cellular transport.
1. Digestion and Absorption at the Macroscopic Level
Dietary carbohydrate is taken principally in the form of
starch, although significant quantities of disaccharides and
monosaccharides are also likely to be present. Hydrolysis of
starch is begun by salivary amylase and is continued by pan-
creatic amylase, to yield maltose and small amounts of glu-
cose. The stomach and intestine may thus be presented with
a complex mixture of partially digested starch, maltose and
other disaccharides (e.g. sucrose and lactose) and mono-
saccharides (e.g. glucose and fructose).
a. Disappearance from the Lumen
In attempts to locate the site of digestion and absorption
of sugars, two rather different experimental approaches have
been made, (i) Sugars are introduced directly into the stomach
and subsequently regions of the gut are isolated and the sugar
content examined, (ii) Regions of the intestine are isolated
initially and their capacity to deal with solutions of sugars, in
vivo or in vitro, is studied.
In many of the early studies, glucose solutions were intro-
duced directly into the stomach, although it is unlikely that
large quantities of glucose are present in the stomach physio-
logically. This approach showed that only small amounts of
glucose were absorbed by the stomach (Maddock, Trimble &
Carey, 1933; Fenton, 1945; Reynell & Spray, 1956) and that
most of the glucose was absorbed from the upper small intes-
tine rather than the lower part (Karr, Abbott, Hoffman &
Miller, 1940; Shay, Gershon-Cohen. Fels & Munro, 1940;
236
Reynell & Spray, 1956). Even when high concentrations were
given, the absorptive capacity of the small intestine was not
easily saturated and glucose was not usually detected in the
colon (Birchall, Fenton & Pierce, 1946; Reynell & Spray,
1956).
The capacity for absorption of monosaccharides varies in
different regions, with a maximum occurring about the middle
of the small intestine in vitro. This was shown in the hamster
for glucose (Crane & Mandelstam, 1960), and in the rat for
glucose (Baker, Searle & Nunn, 1961; Barry, Matthews &
Smyth, 1961) and galactose (Levin & Smyth, 1963). Also the
terminal ileum of the rat showed no ability to transfer these
hexoses against a concentration gradient. Gimrnins & Jussila
(1955) observed in the human intestine about a 40% decrease
in absorption of glucose from the ileum compared with
jejunum, with a similar decrease in urea absorption. In
human foetal intestine also the jejunum has a greater capacity
than the ileum for glucose transport (Koldovsky, Heringov4,
Jirsova, Jirasek & Uher, 1965).
Little absorption of glucose (McNealy & Willems, 1929) or
galactose, fructose and xylose (Davidson & Garry, 1939)
occurred in vivo in the colon, and it has no capacity, in vitro,
for concentrating glucose (Parsons & Paterson, 1960; Cordero
& Wilson, 1961).
Recently investigations have been made into the absorption
of disaccharides. Intubation studies by Dahlqvist & Borgstrom
(1961) indicated that disaccharides might be absorbed at dif-
ferent levels of the human small intestine; lactose was ab-
sorbed in the duodenum and proximal jejunum, maltose in the
jejunum and proximal ileum, and sucrose in the distal jejunum
and ileum. The sites of absorption in man correlated well
with the location of the different disaccharidases in pig intes-
tine (Dahlqvist, 1961), but the results of Malhotra & Philip
(1964) were not in complete agreement with this.
The suggestion that different disaccharides are digested and
absorbed in different regions of the small intestine has not been
substantiated. Maltose (Dahlqvist & Thomson, 1963a) and
sucrose (Dahlqvist & Thomson, 1963b) were both absorbed in
the upper parts of the rat small intestine after feeding by
stomach-tube. These workers also found that disaccharides
were absorbed as rapidly as a mixture of their constituent
monosaccharides. In the case of sucrose, the liberated fructose
was absorbed more slowly than the glucose; fructose could be
recovered from the ileum and large intestine. In man, Gray &
Ingelfinger (1965, 1966) observed that sucrose absorption
occurred more readily in the perfused jejunum than in the
ileum and, in agreement with Dahlqvist & Thomson (1963b;
in rat), that sucrose and its component monosaccharides were
absorbed at similar rates. Comparison of the absorption of
disaccharides from the perfused human jejunum (Gray &
Santiago, 1966) showed that maltose and sucrose were
hydrolysed at similar rates but that lactose hydrolysis was
considerably slower. Furthermore, lactose absorption was
much slower than an equimolar mixture of glucose and
galactose.
It is thus clear that, in the normal adult, hydrolysis is not
likely to be a rate-limiting step in the absorption of maltose
and sucrose but could be so in the case of lactose. This might
not apply in the suckling animal, in which lactase activity is
higher than in the adult, and other disaccharidase activities are
lower (Rubino, Zimbalatti & Auricchio, 1964).
The hydrolytic capacity of homogenates prepared from dif-
ferent regions of the intestinal tract of several species has been
Br. med. Bull. 1967
 ABSORPTION OF CARBOHYDRATES H. Newey
examined by many workers. In general, disaccharidases are
confined to the small intestine, with little activity in the
stomach or colon, although exact locations in the small intes-
tine are not always in agreement. Some of the discrepancies
may be explained by species variation, although experimental
technique—and particularly the precision by which different
regions are located—may also be involved.
Dahlqvist (1961) concluded that maltase and sucrase activi-
ties were predominantly in the distal small intestine of the pig,
with lactase in the upper jejunum and duodenum. In the rat
small intestine, sucrase activity was mainly in the upper half
(Blair & Tuba, 1963; Dahlqvist & Thomson, 1963b), whereas
maltase was fairly evenly distributed throughout (Dahlqvist &
Thomson, 1963a). When the rat intestine was subdivided into
fifths (Rubino et al. 1964), a pronounced reduction in maltase
activity was observed in the terminal fifth (distal ileum), and
maltase, sucrase and lactase showed a similar distribution, with
activities at a maximum in the mid-regions of the gut. This
agrees with a report by Newcomer & McGill (1966), who
found that maltase, sucrase and lactase activities in human
biopsy specimens were low in the duodenum and distal
ileum, and maximal in the jejunum and proximal ileum.
b. Appearance in the Blood Stream
So far, digestive and absorptive activities have been dealt
with by considering disappearance from the intestinal tract
but, since the intestine is presented with carbohydrates in
several forms, it is also necessary to examine the form appear-
ing in the blood stream. Many workers have found increases
in the glucose content of the blood after a carbohydrate meal
(Wilson, 1962), but, because of technical difficulties, few
attempts have been made to recover from the mesenteric blood
all the carbohydrate disappearing from the lumen. Even so, it
is reasonable to conclude from the following evidence that
monosacchandes are the chief form appearing in the mesenteric
venous blood. Lamer & McNickle (1955) examined the portal
blood of rabbits after feeding starch and found only small
quantities of maltose, but the glucose concentration was
almost doubled. In-vitro studies with starch (Wilson &
Vincent, 1955) or starch hydrolysate (Chain, Mansford &
Pocchiari, 1960) showed that glucose was the only product
appearing in the serosal fluid. However, in certain gastro-
intestinal disorders urinary excretion of disaccharides is
observed (Gryboski, Thayer, Gabrielson & Spiro, 1963).
When maltose and sucrose were given by stomach-tube
(Dahlqvist & Thomson, 1963a, 1963b), little—if any—disac-
charide appeared in the urine, although a large urinary excre-
tion was found after intraperitoneal injection. Thus it appears
unlikely that significant quantities of maltose or sucrose can
pass from the intestinal lumen into the blood stream. Further-
more, in-vitro studies (Fridhandler & Quastel, 1955; Wilson &
Vincent, 1955) showed that very little sucrose, but larger quan-
tities of lactose, crossed the intestinal wall. Also in-vivo
studies by Sterk & Kretchmer (1964) showed a marked lactos-
uria, particularly in adult animals after administration of
lactose; this might be correlated with the diminished lactase
activity in adults.
Numerous studies of monosaccharide absorption have been
made (Crane, 1960; Wilson, 1962); and many workers have
demonstrated a rise in blood-sugar concentration. As early
as 1917, Hendrix & Sweet showed that the glucose concentra-
tion of mesenteric venous blood increased after glucose was
237
Vol. 23 No. 3
introduced into the intestine. It was shown by Kiyasu, Katz
& Chaikoff (1956), using the rat, and by Atkinson, Parsons &
Smyth (1957), using the dog, that about 90% of the glucose
leaving the lumen appeared as glucose in the mesenteric
blood, together with small quantities of lactic acid- Corre-
sponding experiments on galactose have not been made but, as
galactose can be recovered almost completely in in-vitro
experiments, it seems likely that it appears, as such, in the
blood stream. Further, after introducing galactose into
human jejunum, Ockerman & Lundborg (1965) measured a
large increase in the galactose concentration of mesenteric
blood and could detect no conversion to glucose.
When fructose was absorbed, glucose (in the guinea-pig) or
lactose (in the rat) appeared in the blood (Kiyasu & Chaikoff,
1957). Species differences in the conversion of fructose during
absorption have been noticed by several authors and reviewed
by Crane (1960) and Wilson (1962). Recently the absorption
products of fructose were examined in man by Holdsworth &
Dawson (1965), Ockerman & Lundborg (1965) and White &
Landau (1965), who found appreciable conversion of fructose
to glucose and sometimes lactate. How important this is in
fructose absorption is not clear, since Ockerman and Lund-
borg concluded that up to 70% of the fructose absorbed was
recovered as glucose from the mesenteric blood, whereas
Holdsworth & Dawson (1965) found a smaller conversion and
suggested that a "separate special transport system" is possible
for fructose.
2. Digestion at the Cellular Level
In discussion of digestion and absorption at the cellular
level, it is usual to assume that both processes occur in the
same columnar epithelial cell, also that all these cells possess
the same functional activity. Regional differences do, how-
ever, exist along the intestine and, although many of these
may be quantitative differences explained, e.g., on the basis of
numbers of cells, there are also functional differences which
perhaps involve different cell types.
Until quite recently it was generally held that digestion was
carried to completion by enzymes secreted into the intestinal
lumen, although isolated reports (Cajori, 1933; Florey,
Wright & Jennings, 1941; Rothstein, Meier & Scharff, 1953;
Borgstrom, Dahlqvist, Lundh & Sjovall, 1957) had suggested
that digestive enzyme activity was associated with cells rather
than with the luminal fluid. More-detailed studies with
disaccharides produced evidence that these were hydrolysed
within the cell (Chain et al. 1960; Dahlqvist & Borgstrom,
1961; Miller & Crane, 1961a; Newey, Sanford & Smyth,
1963; Parsons & Prichard, 1965). It was also concluded that
intracellular peptidases (Newey & Smyth, 1960) and an intra-
cellular monoglyceridase (Senior & Isselbacher, 1963) com-
plete the digestion of protein and fat. All these studies have
established the concept that the terminal stages of digestion
occur within the epithelial cells.
Digestion at the cell membrane is included under the term
"intracellular hydrolysis", and this has been discussed in some
detail by Ugolev (1965). So far, experimental evidence is not
conclusively in favour of membrane digestion but it remains a
real possibility; a convenient feature of this is that penetration
of a lipid membrane by a disaccharide would not have to be
accounted for. Wherever the site of hydrolysis lies, it is clear
that the products of hydrolysis do not equilibrate with the
luminal contents before absorption occurs; in this respect the
 ABSORPTION OF CARBOHYDRATES H. Newey
suggestion of Semenza, Tosi, Vallotton-Delachaux & Mul-
haupt (1964) is of some interest. They observed that sucrase
activity was dependent on Na concentration and they suggested
that, since monosaccharide absorption is also Na-dependent,
a close molecular association exists between the site of
hydrolysis and the site of monosaccharide entry into the cell.
However, their interpretation is not readily acceptable, as they
also found that specific maltase activity was not Na-dependent.
The location of disaccharidases has not been conclusively
determined but, generally, the evidence favours a site within
the brush border. Miller & Crane (1961b) isolated brush
borders of hamster intestine and found they contained most
of the maltase and invertase activities of the cell. Similar cell-
fractionation procedures have been used by other workers
(Carnie & Porteous, 1962; Gitzelmann, Davidson & Osinchak,
1964; Ruttloff, Noack, Friese & Schenk, 1964; Porteous &
d a r k , 1965), but such a definite location of the disaccharidases
was not confirmed, mainly because the brush-border fraction
was contaminated with other cellular material. Examination of
lactase activity led to the conclusion that two lactases were
present having different distributions (Doell & Kretchmer,
1962), with about a third of the activity recoverable from the
brush-border fraction (Koldovsky, Noack, Schenk, Jirsova,
Heringovd, Brand, Chytil & Fridrich, 1965).
A functional approach, using intact everted sacs, was made
by Newey et al. (1963) to determine the site of maltase activity
and its relationship to other cellular activities. Their results
demonstrated, in agreement with Newey, Parsons & Smyth
(1959), that the site of phlorrhizin inhibition of glucose trans-
port was situated near the luminal border of the cell and that
maltase was confined to a compartment on the luminal side of
the phlorrhizin barrier; this compartment could be the brush
border.
3. Absorption at the Cellular Level
Whether monosaccharides are formed in the lumen or in the
brush border, their movement across the cell involves a process
more complicated than diffusion, although diffusion un-
doubtedly occurs at some stage in absorption. In-vitro and
in-vivo studies, using dietary and non-dietary sugars, have
produced a mass of information on monosaccharide absorp-
tion and, while the mechanism is still obscure, certain charac-
teristics have been established.
a. Characteristics of the Transport Process
Specificity. The process of absorption exhibits a high degree
of chemical specificity, since hexoses of similar si2e are absorbed
at very different rates (Cori, 1925; Verzar & McDougall, 1936).
Glucose and galactose are absorbed at similar rates and much
faster than mannose, with fructose occupying an intermediate
position. Clearly, small changes in molecular configuration
produce large changes in absorption. The stereochemical
structure required for participation in the transport process
was obtained (Crane, 1960; Wilson, 1962) by examining the
ability of the intestine to concentrate a variety of sugars and
related compounds. Those concentrated were found to pos-
sess a pyranose ring with a carbon atom attached to C-5 of the
ring, and a hydroxyl group attached to C-2, this OH having
the same stereoconfiguration as in D-glucose. The necessity of
this basic structure is, however, open to question since r>-
xylose, a pentose not having the extra C at C-5 (Csaky &
Lassen, 1964; Alvarado, 1966) and r>mannose, without the
238
required OH configuration at C-2 (Csaky, 1966), were re-
ported to be actively transported.
Saturation. The rate of absorption of some sugars does not
increase proportionally with increase in concentration (Cori,
1925) but approaches a maximum rate at high concentrations
(Fisher & Parsons, 1953a, 1953b). The absorptive process
exhibits saturation kinetics analogous to Michaelis-Menten
kinetics of enzyme reactions, and an attempt to characterize
the absorption of a sugar by determination of its half-satura-
tion concentration or Michaelis constant (JC^) was made by
Fisher and Parsons.
Competition. The rate of absorption of one sugar can be
reduced by the presence of another sugar. The extent of inhi-
bition is dependent on the particular sugars used and on their
concentration; this suggests competition for a specific site in
the transport process. Interference between glucose and
galactose was shown in vivo by Cori (1926) and in vitro by
Fisher & Parsons (1953b). Km values have been used to predict
the degree of inhibition of absorption of one sugar by another;
if the predicted inhibition agreed with the observed inhibition,
it was taken as evidence for a common step in the transport
process. This approach was used by Jorgensen, Landau &
Wilson (1961), who concluded that all transported sugars
compete for a common pathway. This conclusion has been
rather generally accepted (Crane, 1960; Wilson, 1962). There
are, however, several observations which are not readily inter-
preted on the basis that all transported sugars share the same
pathway. Keston (1964) pointed out that some discrepancies
in observed and calculated inhibitions appear in the literature.
Holdsworth & Dawson (1964) found no inhibition by galac-
tose of glucose absorption from human intestine, although the
predicted inhibition was 21 %. Other workers have also
reported findings not entirely in agreement with the idea that
glucose and galactose share only a single common path
(Fisher & Parsons, 1953b; DuRuisseau & QuasteL 1959;
Parsons & Wingate, 1961; Newey, Sanford & Smyth, 1966).
The possibility exists that a second pathway is available to
glucose besides the one shared with galactose.
Active transport. The absorptive process can bring about
movement of sugars against their chemical potential, i.e.,
active transport is said to occur. To concentrate the sugar,
energy from cellular metabolism must be expended, but how
the energy is coupled to transport is not yet understood.
Evidence from in-vivo studies in favour of active transport was
obtained by Barany & Sperber (1939) who showed that glucose
disappeared from the intestinal lumen at a concentration
lower than that in the blood stream; Atkinson et al. (1957)
showed that glucose entered the mesenteric blood when the
blood-glucose concentration was higher than the luminal
concentration. Active transport of glucose and galactose in
vitro was first shown by Fisher & Parsons (1953a, 1953b) and
has since been well documented (see Wilson, 1962).
Inhibition. The absorption of sugars can be inhibited by a
number of substances present in low concentration. Some
inhibitors are highly specific, e.g. phlorrhizin (Nakazawa,
1922), whereas others are more generally toxic, e.g. metabolic
inhibitors interfering with the production and utilization of
energy. This aspect has been treated in more detail in the
paper by Sanford, p. 270 of this Bulletin.
Ionic dependence. The absorption of sugars is influenced by
the concentration of ions. Particularly important is the Na ion,
which was shown by Rilclis & Quastel (1958) to be essential
for glucose absorption. This association between Na and
Br. med. Bull. 1967
 ABSORPTION OF CARBOHYDRATES H. Newey
sugar transport has been confirmed and extended by several
workers, in vitro (Csaky & Thale, 1960; Rummel & Stupp,
1960; Parsons & Wingate, 1961; Bihler & Crane, 1962;
Bosadkova & Crane, 1965), and in vivo (Csaky & Zollicoffer,
1960; Lluch & Ponz, 1963). Further, ouabain, an inhibitor of
Na movement in several tissues (see Ghynn, 1964), including
the intestine (Schultz & Zalusky, 1964a), also inhibits sugar
absorption (Csaky, 1963; Csaky & Hara, 1965). The inter-
action of Na with the sugar-transport system is not yet under-
stood and is receiving much attention. It is clear, however,
that Na is involved not only in intestinal sugar transport
but also in several other transport processes. Intestinal
sugar transport is less responsive to concentration changes
of other ions. Omitting K caused a small inhibition (Riklis
& Quastel, 1958; Bihler & Crane, 1962), but increasing
the K level produces variable effects. With 15 m-equiv. K/L,
Riklis and Quastel found about 50% stimulation in vitro, but
Bihler and Crane found inhibition. Larralde, Bello & Fer-
nandez-Otero (1962) showed inhibition of glucose absorption
in vivo with high K. concentration, while Csaky & Ho (1966)
found stimulation of glucose absorption with no effect on
galactose, and concluded that K was not affecting a specific
transport system but was stimulating glucose metabolism,
thereby increasing entry into the cells. The variability might
be explained on the basis that transport is not dependent
simply on the K concentration but on the Na: K concentration
ratio. Changing the anion composition of the medium had
little effect on absorption (Bihler & Crane, 1962).
Electrical activity. The absorption of sugars produces
changes in the electrical activity of the intestine. This aspect
has been dealt with in the paper by Barry, p. 266 of this
Bulletin.
It is evident from all these characteristics that absorption of
monosaccharides is a complex process and one which still
presents several problems at the cellular and molecular levels.
Two important questions to be answered are: (i) where in the
cell is the process situated ? (ii) how is the sugar moved across
the cell against its concentration gradient?
b. Cellular Location of the Transport Process
Different approaches have led to the conclusion that the
transport process, or at least one stage of it, exists at or near
the luminal membrane of the celL Newey et al. (1959) showed
that a phlorrhizin-sensitive stage in glucose transport was
situated near the luminal membrane. Whether this is the only
stage, in the sense that it concentrates sugar within the cell
and that subsequent movement from the cell across the serosal
membrane is by diffusion, has not been established. Different
possibilities in the location of the concentrating mechanism
were discussed by Newey & Smyth (1966).
McDougal, Little & Crane (1960) prepared sections of
hamster intestine after incubation with galactose, found that
the epithelial section contained higher galactose concentra-
tions than the core of the villi and thus concluded that the
concentrating mechanism is in the luminal border. An auto-
\ radiograph technique (Kinter & Wilson, 1965) showed an
increase in sugar concentration in passing from the lumen to
the epithelial cell, again indicating active transport at the
luminal border.
The question remains whether movement of sugar from the
cells can be accounted for simply by diffusion. The effects of
inhibitors on intestinal glucose transport were interpreted
239
Vol. 23 No. 3
(Detheridge, Matthews & Smyth, 1966) in favour of a two-
stage process consisting of entry by facilitated diffusion, with
the concentrating mechanism nearer the serosal pole of the
celL Also, Rossi, Lippe & Capraro (1962) concluded that Na
transport was necessary for movement of glucose from the
cells, as this could not be explained by diffusion.
c. Mechanism of Monosaccharide Transport
Current concepts of transport rest heavily on the carrier
hypothesis. A carrier is assumed to be a mobile component of
the membrane, possessing specific chemical groups or sites to
which the sugar molecule can attach. Diffusion of the sugar-
carrier complex would move the sugar across the lipid barrier
of the membrane, with subsequent release of the sugar into the
cell. Such a carrier process could account for the charac-
teristics of specificity, saturation and competition, but so far a
carrier has not been isolated and its nature is quite unknown.
(Christensen (1960) and Wilbrandt & Rosenberg (1961) have
presented a general discussion of carrier transport.)
A carrier functioning as outlined above could equilibrate
the luminal and intracellular sugar concentrations, but active
transport would not occur. To concentrate the sugar, the
carrier must be coupled in some manner to a source of energy
and there are several indications that Na is involved at this
stage. Csaky (1963) has suggested that Na is necessary for the
utilization of adenosine triphosphate (ATP), probably by
influencing the activity of a membrane ATPase. In other
words Na affects the supply of energy from ATP to the trans-
port process, but how the energy is coupled to sugar transport
remains unanswered. Evidence that intestinal ATPase is
dependent on a critical Na concentration was provided by
Taylor (1962).
Crane (1962) put forward the interesting idea that sugar
movement is dependent on the Na gradient across the luminal
membrane. He suggested that a Na-sugar-carrier complex
moves across the luminal membrane in response to the
difference in Na concentration between the lumen and the cell,
this difference being maintained by an energy-dependent Na
pump which returns Na to the lumen. Schultz & Zalusky
(1964b) modified Crane's hypothesis by siting the Na pump at
the serosal membrane on the evidence that serosal ouabain
was more effective than mucosal ouabain in inhibiting Na
transport.
Additional information on the interaction between Na and
sugar transport was obtained by Crane, Forstner & Eichholz
(1965), who found that the concentration of Na influenced the
affinity of the carrier for sugar. A low Na concentration within
the cell might produce a low-affinity carrier, thereby allowing
the dissociation of sugar from the carrier. A difference of
carrier-sugar affinity between the two sides of the membrane
could in itself bring about accumulation of sugar against a
concentration gradient, and Crane's original postulate of a
Na-sugar-carrier complex moving across the membrane may
be superfluous. Csaky (1963) in fact produced evidence that
carrier-mediated transport of sugar, in that it was inhibited by
phlorrhizin, could occur in the absence of Na. It may turn out
that the link between the concepts of Crane (Na concentration
influences affinity) and Csaky (Na concentration influences
ATPase activity and ATP utilization) is that ATP utilization
alters the affinity of the carrier for sugar. One point is clear:
that the mechanism of transport still presents many problems,
and further experiments are required to answer them.
 ABSORPTION OF CARBOHYDRATES H. Newey
REFERENCES
Alvarado, F. (1966) Biochim. biopkys. Acta, 112,292
Atkinson, R. M., Parsons, B. J. & Smyth, D. H. (1957) / . Physiol,
Land. 135, 581
Baker, R. D., Searle, G. W. & Nunn, A. S. (1961) Am. J. Physiol.
200,301
Barany, E. & Sperber, E. (1939) Skand. Arch. Physiol. 81, 290
Barry, B. A., Matthews, J. & Smyth, D. H. (1961) / . Physiol.,
Lond. 157, 279
Bihler, I. & Crane, R. K. (1962) Biochim. biophys. Acta, 59,78
Birchall, E. F., Fenton, P. F. & Pierce, H. B. (1946) Am. J.
Physiol. 146, 610
Blair, D. G. R. & Tuba, J. (1963) Can. J. Biochem. Physiol. 41,905
BorgstrSm, B., Dahlqvist, A., Lundh, G. & Sjavall, J. (1957)
/ . c/m./nv«/.36,1521
BosaSkova, J. & Crane, R. K. (1965) Biochim. biophys. Acta, 102,
423
Cajori, F. A. (1933) Am. J. Physiol. 104, 659
Carnie, J. A. & Porteous, J. W. (1962) Biochem. J. 85, 620
Chain, E. B., Mansford, K. R. L. & Pocchiari, F. (1960) / .
Physiol, Lond. 154, 39
Christensen, H. N. (1960) Adv. Protein Chem. 15, 239
Cordero, N. & Wilson, T. H. (1961) Gastroenterology, 41, 500
Cori, C. F. (1925) / . biol. Chem. 66, 691
Cori, C. F. (1926) Proc. Soc. exp. Biol. Med. 23,290
Crane, R. K. (1960) Physiol. Rev. 40, 789
Crane, R. K. (1962) Fedn Proc. Fedn Am. Socs. exp. Biol. 21, 891
Crane, R. K., Forstner, G. & Eichholz, A. (1965) Biochim.
biophys. Acta, 109, 467
Crane, R. K. & Mandelstam, P. (1960) Biochim. biophys. Acta,
45,460
Csaky, T. Z. (1963) Fedn Proc. Fedn Am. Socs exp. Biol. 22, 3
Csaky, T. Z. (1966) Life Sci. 5,1025
Csaky, T. Z. & Hara, Y. (1965) Am. J. Physiol. 209, 467
Csaky, T. Z. & Ho, P. M. (1966) / . gen. Physiol. 50,113
Csaky, T. Z. & Lassen, U. V. (1964) Biochim. biophys. Acta, 82,
215
Csaky, T. Z. & Thale, M. (1960) / . Physiol., Lond. 151, 59
Csaky, T. Z. & Zollicoffer, L. (1960) Am. J. Physiol. 198, 1056
Cummins, A. J. & Jussila, R. (1955) Gastroenterology, 29, 982
Dahlqvist, A. (1961) Biochem. /. 78,282
Dahlqvist, A. & BorgstrSm, B. (1961) Biochem. J. 81,411
Dahlqvist, A. & Thomson, D. L. (1963a) Acta physiol. scand. 59,
111
Dahlqvist, A. & Thomson, D. L. (1963b) / . Physiol., Lond. 167,
193
Davidson, J. N. & Garry, R. C. (1939) / . Physiol, Lond. 96,172
Detheridge, J. F., Matthews, J. & Smyth, D. H. (1966)/. Physiol,
Lond. 183, 369
Doell, R. G. & Kretchmer, N. (1962) Biochim. biophys. Acta, 62,
353
DuRuisseau, J. P. & Quastel, J. H. (1959) Proc. Soc. exp. Biol.
Med. 100, 711
Fenton, P. F. (1945) Am. J. Physiol. 144,609
Fisher, R. B. & Parsons, D. S. (1953a) / . Physiol, Lond. 119, 210
Fisher, R. B. & Parsons, D. S. (1953b) / . Physiol, Lond. 119, 224
Florey, H. W., Wright, R. D. & Jennings, M. A. (1941) Physiol.
Rev. 21, 36
Fridhandler, L. & Quastel, J. H. (1955) Archs Biochem. 56,412
Gitzelmann, R., Davidson, E. A. & Osinchak, J. (1964) Biochim.
biophys. Acta, 85, 69
Glynn, I. M. (1964) Pharmac. Rev. 16, 381
Gray, G. M. & Ingelfinger, F. J. (1965) / . din. Invest. 44, 390
Gray, G. M. & Ingelfinger, F. J. (1966)/. din. Invest. 45, 388
Gray, G. M. & Santiago, N. A. (1966) Gastroenterology, 51, 489
Gryboski, J. D., Thayer, W. R., jr, Gabrielson, I. W. & Spiro,
H. M. (1963) Gastroenterology, 45,633
Hendrix, B. M. & Sweet, J. E. (1917)/. biol. Chem. 32,299
Holdsworth, C. D. & Dawson, A. M. (1964) Clin. Sci. 27, 371
Holdsworth, C. D. & Dawson, A. M. (1965) Proc. Soc. exp. Biol.
Med. 118, 142
Jorgensen, C. R., Landau, B. R. & Wilson, T. H. (1961) Am. J.
Physiol. 200, 111
Karr, W. G., Abbott, W. O., Hoffman, O. D. & Miller, T. G.
(1940) Am. J. med. Sci. 200, 524
240
Keston, A. S. (1964) Science, N. Y. 143, 698
Kinter, W. B. & Wilson, T. H. (1965)/. Cell Biol. 25, No. 2, pt 2,
p. 19
Kiyasu, J. Y. & Chaikoff, L L. (1957)/. biol Chem. 22A, 935
Kiyasu, J. Y., Katz, J. & Chaikoff, I. L. (1956) Biochim. biophys.
Acta, 21, 286
Koldovsky, O., Heringova, A., Jirsova, V., Jirasek, J. E. & Uher,
J. (1965) Gastroenterology, 48,185
Koldovsky, O., Noack, R., Schenk, G., Jirsova, V., Heringova, A.,
Brand, H., Chytil, F. & Fridrich, M. (1965) Biochem. / . 96,492
Lamer, J. & McNiclde, C. M. (1955) Fedn Proc. Fedn Am. Socs
exp. Biol. 14,242
Larralde, J., Bello, J. & Fernandez-Otero, P. (1962) Revta esp.
Fisiol 18, 127
Levin, R. J. & Smyth, D. H. (1963) / . Physiol, Lond. 169, 755
Lluch, M. & Ponz, F. (1963) Revta esp. Fisiol. 19,187
McDougal, D. B., jr, Little, K. D. & Crane, R. K. (1960) Biochim.
biophys. Acta, 45, 483
McNealy, R. W. & Willems, J. D. (1929) Surgery Gynec. Obstet.
49,794
Maddock, S. J., Trimble, H. C. & Carey, B. W., jr (1933) / . biol
Chem. 103, 285
Malhotra, O. P. & Philip, G. (1964) Ind. J. med. Res. 52,68
Miller, D. & Crane, R. K. (1961a) Biochim. biophys. Acta, 52, 281
Miller, D. & Crane, R. K. (1961b) Biochim. biophys. Acta, 52,293
Nakazawa, F. (1922) TohukuJ. exp. Med. 3,288
Newcomer, A. D. & McGill, D. B. (1966) Gastroenterology, 51,
481
Newey, H., Parsons, B. J. & Smyth, D. H. (1959) / . Physiol,
Lond. 148, 83
Newey, H., Sanford, P. A. & Smyth, D. H. (1963) / . Physiol,
Lond. 168, 423
Newey, H., Sanford, P. A. & Smyth, D. H. (1966) / . Physiol,
Lond. 186, 493
Newey, H. & Smyth, D. H. (1960) / . Physiol, Lond. 152, 367
Newey, H. & Smyth, D. H. (1966) In: Bartelheimer, H., Heyde,
W. & Thorn, W., ed. D-Glucose und Venvandte Verbindungen
in Medizin und Biologie, p. 277. Ferdinand Enke, Stuttgart
Ockerman, P. A. & Lundborg, H. (1965) Biochim. biophys. Acta,
105,34
Parsons, D. S. & Paterson, C. R. (1960) Biochim. biophys. Acta,
41, 173
Parsons, D. S. & Prichard, J. S. (1965) Nature, Lond. 208,1097
Parsons, D. S. & Wingate, D. L. (1961) Biochim. biophys. Acta,
46,170
Porteous, J. W. & Clark, B. (1965) Biochem. J. 96,159
Reynell, P. C. & Spray, G. H. (1956)/. Physiol, Lond. 134, 531
Riklis, E. & Quastel, J. H. (1958) Can. / . Biochem. Physiol 36,
347
Rossi, S., Lippe, C. & Capraro, V. (1962) Experientia, 18, 325
I
Rothstein, A., Meier, R. C. & Scharff, T. G. (1953) Am. J. Physiol
173, 41
Rubino, A., Zimbalatti, F. & Auricchio, S. (1964) Biochim.
biophys. Acta, 92, 305
Rummel, W. & Stupp, H. F. (1960) Arch. exp. Path. Pharmak.
240,79
Ruttloff, H., Noack, R., Friese, R. & Schenk, G. (1964) Biochem.
Z. 341, 15
Schultz, S. G. & Zalusky, R. (1964a) /. gen. Physiol 47, 567
Schultz, S. G. & Zalusky, R. (1964b) /. gen. Physiol 47,1043
Semenza, G., Tosi, R., Vallotton-Delachaux, M. C. & MUlhaupt,
E. (1964) Biochim. biophys. Acta, 89, 109
Senior, J. R. & Isselbacher, K. J. (1963) / . clin. Invest. 42,187
Shay, H., Gershon-Cohen, J., Fels, S. S. & Munro, F. L. (1940)
Am. J. dig. Dis. 7,456
Sterk, V. V. & Kretchmer, N. (1964)Pediatrics, Springfield, 34,609
Taylor, C. B. (1962) Biochim. biophys. Acta, 60, 437
Ugolcv, A. M. (1965) Physiol. Rev. 45, 555
Verzar, F. & McDougall, E. J. (1936) Absorption from the intestine.
Longmans, Green, London
White, L. W. & Landau, B. R. (1965)/. clin. Invest. 44,1200
Wilbrandt, W. & Rosenberg, T. (1961) Pharmac. Rev. 13,109
Wilson, T. H. (1962) Intestinal absorption. Saunders, Philadelphia,
Pa
Wilson, T. H. & Vincent, T. N. (1955)/. biol Chem. 216, 851
Br. med. Bull 1967