Lactose is the primary carbohydrate for breast-fed and most formula-fed
infants. It consists of glucose and galactose linked by an α-1,4
glycosidic bond. Lactase-mediated hydrolysis is the rate-limiting
step in lactose assimilation. Lactase is localized to the microvilli
of enterocytes at the villous tips, and its expression is developmentally regulated.
A low level of lactase activity is present by 11 weeks of gestation
and increases to 25% of term levels by 34 weeks. It peaks
at birth in term infants and then declines to approximately 25% of term
levels by 1 year of age. Despite the high levels of lactase activity
in early infancy, the large quantities of lactose that are ingested
daily (approximately 10–14 g/kg) overwhelm the
absorptive capacity of the small intestine, and a large amount of
ingested lactose reaches the colon. Intestinal bacteria further
digest the lactose to organic acids that are absorbed, salvaging
nutrient calories for the infant. Further decline in lactase activity
during mid to late childhood leads to lactose intolerance in much
of the world’s population. It is a benign condition, but
diarrhea and bloating can cause substantial discomfort and inconvenience.
After weaning, most carbohydrate is ingested in the form of starch,
sucrose, glucose and fructose. Starch or amylopectin,
is a glucose polymer linked by both α-1,4 and α-1,6
linkages. Starch is initially hydrolyzed by salivary and pancreatic
amylases to generate substrates recognized by the brush border hydrolases
glucoamylase and maltase. Both amylases have nearly identical structures,
and both are potent endoglycosidases. They act at the internal α-1,4
bonds of amylose and amylopectin to produce some glucose but mainly
trioses, disaccharides, and limit dextrins, which are then sequentially
hydrolyzed by the brush border α-glucosidases:
(1) glucoamylase, (2) isomaltase, and (3) sucrase. In the neonate,
the quantitative contribution of salivary and pancreatic amylase
to starch digestion is poorly defined. Salivary amylase secretion
is present in the preterm infant by 34 weeks of gestation, but no
pancreatic amylase secretion can be demonstrated until 4 to 6 months
after birth, when starches normally are introduced into the infant
diet. Salivary amylase is thought to be of minimal quantitative
importance for carbohydrate digestion in the adult, but a more significant
role has been postulated in the preterm infant. The brush border
enzyme glucoamylase hydrolyzes the products of amylase digestion.
It has maximum activity for oligomers containing between 5 and 9
glucose residues, and higher-molecular-weight compounds or complex
carbohydrates with multiple branch points are less efficiently hydrolyzed.
Glucoamylase is detectable by 20 weeks of gestation, and levels
increase throughout gestation so that by 34 weeks activity is similar
to that of older children. Developmental regulation and the role
of diet on pancreatic amylase and intestinal hydrolase expression
are now being investigated at a molecular level. Clinically significant
starch intolerance is relatively rare in infancy beyond the neonatal
period. Sucrose is digested by sucrase-isomaltase, a major intestinal
brush border enzyme that is first synthesized as a single-chained
precursor containing active sites for sucrose and isomaltose hydrolysis. It
undergoes extensive intracellular modification before being incorporated
into the brush border membrane, where it is rapidly cleaved by pancreatic
proteases into the two subunits sucrase and isomaltase. Despite
proteolytic cleavage, the subunits remain associated and fully active,
being responsible for the hydrolysis of sucrose, isomaltose, and
maltose. In the human infant, sucrase-specific activity is high
by 20 weeks of gestation, being nearly equal to one half to three
quarters the full-term infant and adult values. The jejunal-specific
activity of sucrase-isomaltase in full-term infants and adults is
nearly twice that of lactase, making monosaccharide absorption,
rather than hydrolysis, the rate-limiting step in the assimilation
of sucrose. Nondigestible carbohydrates that comprise the structural
component of plants constitute dietary fiber. Fiber cannot be hydrolyzed
by mammalian intestinal enzymes but is hydrolyzed in the colon by
bacterial enzymes.
The final step in the assimilation of carbohydrates after luminal
or brush border hydrolysis is absorption of monosaccharides. Glucose,
galactose, and fructose are transported across the enterocyte into
the portal circulation by passive and active transport mechanisms.
Glucose and galactose transport occurs by two mechanisms: simple,
non saturable diffusion (if luminal concentration exceeds 3 mmol/L)
and active transport. The active transport mechanism is mediated
at the brush border by a Na+-coupled glucose
transporter, SGLT-1, which provides the basis for including glucose
and sodium chloride in oral rehydration solution. The facultative
glucose transporter, GLUT-2, is located on the basolateral membrane.
The glucose transporter is stereospecific for d-glucose
and d-galactose. Active glucose transport can be
demonstrated in vitro at 10 weeks of gestation, and the transporter
is present throughout the entire intestine by 17 to 20 weeks of
gestation, with activity increasing throughout gestation. Mutations
of the SGLT-1 gene have been shown to cause glucose-galactose malabsorption,
which can result in fatal diarrhea in newborn infants. Fructose
is transported either by facilitated diffusion or by a high-affinity
glucose-dependent facultative transporter, GLUT-5, located on the
enterocyte brush border. When large amounts of fructose are ingested
without glucose, as in fruit juices, transport mechanisms may be
overwhelmed, causing diarrhea.