2. Digestion of
carbohydrates
• The principal sites of carbohydrate digestion are mouth
and small intestine.
• The dietary carbohydrates consists of:
Polysaccharides – Starch, glycogen, cellulose.
Disaccharides – Sucrose, maltose, lactose.
Monosaccharides – Mainly glucose and fructose
• Monosaccharides need no digestion prior to absorption
whereas disaccharides and polysaccharides must be
hydrolyzed to simple sugars before their absorption
3. Digestion in mouth
• Digestion of carbohydrates begin in mouth.
• Salivary glands secrete α-amylase (ptyalin) which
initiates hydrolysis of starch.
• During mastication, salivary α-amylase acts briefly on
dietary starch in random manner breaking some α(1→4)
bonds hydrolyzing them to dextrin.
• Carbohydrate digestion halts temporarily in stomach
because the high acidity inactivates the salivary α-
amylase.
4. Digestion in Intestine
• Further digestion of carbohydrates occurs in the small
intestine by pancreatic enzymes. There are two phases of
intestinal digestion.
Digestion due to pancreatic α-amylase.
Digestion due to intestinal enzymes – sucrase, maltase, lactate,
isomaltase.
Digestion due to pancreatic α-amylase
• The function of pancreatic α-amylase is to degrade dextrins
further into a mixture of maltose, Isomaltose and α-limit
dextrin.
• The α-limit dextrins are smaller oligosaccharides containing 3
to 5 glucose units
5. Digestion due to intestinal enzymes
• Enzymes responsible for the final phase of carbohydrate digestion
are located in the brush bordered membrane.
• The enzymes and the reactions they catalyze are as follows:
• The end products of carbohydrate digestion are glucose, fructose
and galactose which are readily absorbed through the intestinal
mucosal cells into the blood stream.
6.
7.
8. Absorption of
Carbohydrates
• Carbohydrates are absorbed as monosaccharides from
the intestinal lumen.
• Two mechanisms are responsible for the absorption of
monosaccharides.
Active transport against concentration gradient i.e. from a low
glucose concentration to a higher concentration.
Facilitative transport, with concentration gradient i.e. from a
higher concentration to lower one.
9. Active transport
• The transport of glucose and galactose across the brush
bordered membrane of mucosal cells occurs by an active
transport.
• Active transport is an energy requiring process that requires a
specific transport protein and presence of sodium ions.
• A sodium dependent glucose transporter (SGLT-1) binds both
glucose and Na+
at separate sites and transports them both
through plasma membrane of intestinal cell.
• The Na+
is transported down its concentration gradient and at
the same time glucose is transported against its concentration
gradient.
• The free energy required for the active transport is obtained
from hydrolysis of ATP linked to a Na+ pump that expels Na+
from the cell in exchange of K+
10. Facilitative transport
• Fructose and mannose are transported across the brush
border by a Na+
independent facilitative diffusion
process, requiring specific glucose transporters, GLUT-5.
• Movement of sugar in facilitative diffusion is strictly
from higher concentration to lower one until it reaches
equilibrium.
• The same transport occurs for glucose and galactose if
concentration gradient is favorable.
11.
12. Clinical aspects
• Lactose intolerance – Defect in enzyme lactase is the
most common disaccharide deficiency . Lactose
accumulates in the gut which undergoes bacterial
fermentation with production of H2 and CO2. Abdominal
cramps occur leading to diarrhea and dehydration.
• Sucrase deficiency – The deficiency of enzyme sucrase
causes intolerance to dietary sources. It is treated by
removal of sucrose from diet.
13. Glucose transporters
• Glucose transporters are facilitative transporters that carry
hexose sugars across the membrane without requiring energy.
• They comprise a family of at least 14 members.
• The most well characterized members of the family are
GLUT1, GLUT2, GLUT3, GLUT4 and GLUT5.
• The transporters belong to a class of proteins called solute
carriers.
• Although GLUT2, -5, -7, -8, -9, -11 and -12 can all transport
fructose, GLUT5 is the only transporter that exclusively
transports fructose.
• Recently, evidence has shown that cell surface receptor for the
human T cell leukemia virus is ubiquitous GLUT1
14. GLUT1
• Ubiquitous: e.g. RBC, placenta, brain, retina, colon,
kidneys. It is the major GLUT in fetus and tissue culture
cells.
• Low Km (35-90 mg/dl), high affinity
• Facilitated diffusion.
• Liver, adipose tissue, muscle cell also expresses GLUT1
during starvation.
• Dysfunction can cause hypoglycorrachia (low CSF
glucose), but normal blood glucose.
15. GLUT2
• Liver, intestine kidneys, beta cells of pancreas.
• High Km (about 450 mg/dl) and high Vmax
• Facilitated diffusion and bidirectional.
• It has high Km, its presence is ideally suited for sensing high
glucose level and release of insulin. So this enables pancreas
to monitor glucose level and adjust rate of insulin secretion.
• In humans, an inactivating mutation of GLUT2 is present in
Fanconi-Bickel syndrome, a rare autosomal recessive disorder
of carbohydrate metabolism, characterized by fasting
hypoglycemia, hepatorenal glycogen accumulation, glucose
and galactose intolerance, and a characteristic proximal
tubular nephropathy.
16. GLUT3
• Ubiquitous: E.g. brain, placenta, kidneys.
• Lowest Km
• Facilitated diffusion of glucose in brain
• Liver, adipose tissue, muscle cell also expresses GLUT3
during starvation.
• GLUT3 is most known for its specific expression
in neurons and has originally been designated as the
neuronal GLUT.
• Has higher affinity for glucose than GLUT1, -2 and -4.
17. GLUT4
• Skeletal muscle, adipocytes, heart
• Low Km (36-90 mg/dl)
• Under the control of insulin.
• Insulin promotes the translocation of intracellular
GLUT4 molecules to the cell surface and thus increases
glucose uptake. In Type 2 diabetes mellitus membrane
GLUT4 is reduced leading to insulin resistance in muscle
and fat cells. In diabetes, entry of glucose into muscle is
only half of normal cells
18. GLUT5
• GLUT5 is a fructose transporter expressed on the apical
border of enterocytes in the small intestine.
• GLUT5 is also expressed in skeletal muscle, testis,
kidney, fat tissue (adipocytes), and brain.
• Facilitated diffusion of fructose
• Fructose malabsorption or Dietary Fructose Intolerance
is a dietary disability of the small intestine, where the
amount of fructose carrier in enterocytes is deficient.
19. • GLUT6 - GLUT6 does not mediate glucose uptake and is
localized on lysosomal membranes. We conclude that GLUT6
is a lysosomal transporter that is regulated by inflammatory
stimuli and modulates inflammatory responses by affecting
the metabolic shift in macrophages.
• GLUT7 - GLUT7 is primarily expressed in the small intestine
and colon, transport glucose from ER to cytoplasm.
• GLUT8 - GLUT8 is expressed mostly
in neurons and testis. being expressed at high levels in testes
and in the acrosomal part of spermatozoa. Furthermore,
GLUT8 appears to play an important role in the energy
metabolism of sperm cells
• GLUT9, which has multiple isoforms in humans is expressed
mainly in the proximal tubule of the kidney and in the liver
and placenta.
20. • GLUT10 - Located in cells of tissues—for example,
skeletal muscle, heart, lung, brain, placenta, kidney, liver
and pancreas.
• GLUT11 - GLUT11 facilitates the transport of both
glucose and fructose.
• GLUT12 - GLU12 is expressed in cells of adipose tissue,
small intestine, skeletal muscle and placenta.
• GLUT13 - GLUT13 is expressed in adipose tissue and
kidney cells. It is also predominantly expressed in the
brain, especially in the hippocampus, hypothalamus,
cerebellum and brain stem.
21. SGLUT
• Sodium-dependent glucose cotransporters (or sodium-
glucose linked transporter, SGLT) are a family of glucose
transporter found in the intestinal mucosa (enterocytes) of
the small intestine (SGLT1) and the proximal tubule of
the nephron.
• A membrane bound carrier protein is involved which carries
glucose along with sodium. This sodium is later expelled by
sodium pump with utilization of energy.
• The transporter in intestine is SGluT1 and the transporter in
kidney is SGluT2. The first one is involved in glucose-galactose
malabsorption and latter is defective in congenital renal
glycosuria.
• Common treatment for diarrhea is oral rehydration fluid. It
contains glucose and sodium together which allows absorption
of sodium to replenish body sodium chloride level and glucose
to provide energy.
