Digestion, absorption, and overview of pathways of carbohydrate metabolism

1. R. C. Gupta
Professor and Head
Department of Biochemistry
National Institute of Medical Sciences
Jaipur, India
Carbohydrate Metabolism
An Overview

2. Carbohydrates constitute the largest
component of an average diet
The most important function of
carbohydrates is to provide energy
Some tissues, e.g. brain and erythrocytes,
get energy almost exclusively from glucose

3. If the conditions become anaerobic, only
glucose can be used as a fuel
During prolonged exercise, even muscles
depend upon glucose as a source of energy
Besides providing energy, carbohydrates
perform some other functions also

4. Some carbohydrates act as structural
constituents of tissues
Ribose and deoxyribose are used to
synthesize nucleotides and nucleic acids
Some carbohydrates form the prosthetic
group of hormones, immunoglobulins, blood
group substances etc

5. Digestion
Carbohydrates are consumed in diet
mostly as polysaccharides
Dietary polysaccharides include starch,
glycogen, cellulose etc
Small amount of disaccharides and mono-
saccharides are also present in food

6. Disaccharides and monosaccharides
present in diet include sucrose, lactose,
fructose, glucose etc
The intestinal mucosa can absorb only
monosaccharides
Larger carbohydrates are hydrolysed into
monosaccharides during digestion

7. Enzymes that
can digest
carbohydrates
are present in:
Saliva
Pancreatic juice
Intestinal secretion

8. Saliva contains an amylase which can
hydrolyse starch and glycogen
But food stays in the mouth for a very
short period
Contribution of salivary amylase in the
digestion of carbohydrates is very small

9. Digestion of carbohydrates really begins in
the small intestine
The next digestive secretion that can
digest carbohydrates is pancreatic juice
Pancreatic juice also contains an amylase

10. Pancreatic amylase
(a-amylase):
Acts at an alkaline pH
Hydrolyses the internal a-1,4-glyco-
sidic bonds of starch and glycogen
Converts starch and glycogen into
maltose, isomaltose and maltotriose

11. Amylase does not act on:
Terminal a-1,4-glycosidic bonds
The a-1,6-glycosidic bonds
present at branch points

13. Intestinal secretion
contains various
disaccharidases:
Maltase
Isomaltase
Sucrase
Lactase

14. Maltase hydrolyses maltose and malto-
triose into glucose
Isomaltase (a-1,6-glucosidase) hydrolyses
isomaltose into glucose
Sucrase (invertase) hydrolyses sucrose
into glucose and fructose
Lactase hydrolyses lactose into glucose
and galactose

16. Hereditary lactase deficiency in children
can cause lactose intolerance
Acquired lactase deficiency can occur in
adults
Lactase deficiency can cause diarrhoea
and flatulence on ingestion of milk

17. Thus, the major products of digestion of
carbohydrates are glucose, fructose and
galactose
Small amounts of mannose, ribose,
xylose etc may also be present in food

18. Cellulose cannot be digested in human
beings but its presence in food is
important
Cellulose stimulates peristalsis and helps
in bowel movement

19. Absorption
Monosaccharides are absorbed mainly in
the small intestine
Purpose of absorption is to transfer
monosaccharides from the intestine into
the circulation

20. Monosaccharides are absorbed from the
lumen of intestine into the mucosal cells
From mucosal cells, they are released into
portal circulation
Portal blood delivers the monosaccharides
to the liver

21. All the pathways of carbohydrate
metabolism are present in liver
Circulating glucose is taken up and utilized
by all the tissues
Liver also releases glucose into systemic
circulation

22. There are two mechanisms for
absorption of monosaccharides
from the intestine:
Active transport
Facilitated diffusion

23. For active transport, the
monosaccharides should have:
A pyranose ring structure with a
methyl or a substituted methyl group
on carbon 5
An –OH group on carbon 2 having
the same configuration as in
D-glucopyranose

24. Other monosaccharides are absorbed by
facilitated diffusion
Monosaccharides meeting the criteria for
active transport are glucose and galactose

26. Active transport
Occurs against concentration gradient
Energy is spent to move the compound
from lower to higher concentration
A carrier (a protein molecule) is
required for active transport
The process is saturable

27. Glucose is absorbed actively from the
intestinal lumen into the mucosal cells by
Sodium Glucose Transporter (SGLT 1)
SGLT 1, present in the cell membrane,
has two binding sites – one for sodium
and the other for glucose
Sodium and glucose, present in the
lumen, bind to SGLT 1

28. Sodium Glucose

29. Concentration of sodium in the lumen of
the intestine is much higher than in the
mucosal cells
At the same time, glucose is transported
into the mucosal cells against its
concentration gradient
Sodium is transported into the mucosal
cells down its concentration gradient

30. The intracellular sodium concentration has
to be kept low
For this, sodium is actively pumped out of
mucosal cells into the capillaries
A rise in sodium concentration in intra-
cellular fluid is physiologically intolerable

31. For every three sodium ions pumped out,
two potassium ions move into the cell
Pumping of sodium occurs against its
concentration gradient

32. Ejection of sodium against its concen-
tration gradient requires energy
Energy is provided by hydrolysis of ATP
into ADP and Pi
The hydrolysis is catalysed by membrane-
bound Na+, K+-exchanging ATPase

33. Thus, transport of glucose into mucosal
cells tends to disturb sodium homeostasis
Energy is spent really to maintain sodium
homeostasis
The system that exchanges sodium and
potassium ions is also known as sodium
pump or sodium-potassium pump

34. Galactose is also absorbed similarly by
SGLT 1
Active transport is disrupted by ouabain
which inhibits the sodium pump
Active transport is also disrupted by
phlorhizin which displaces sodium from
the carrier

35. Facilitated diffusion
Occurs down the concentration
gradient
Carrier (a protein) is required
No energy is required

36. After a meal, fructose concentration in the
lumen of intestine increases
The concentration becomes higher than
in mucosal cells
Fructose is absorbed into mucosal cells
by facilitated diffusion
The carrier involved in fructose transport
is GLUT 5

37. GLUT5 is present on luminal side of the
mucosal cells
Another transporter, GLUT 2, is present on
the contra-luminal side
GLUT2 transports glucose, galactose and
fructose by facilitated diffusion

38. Concentration of glucose, galactose and
fructose in mucosal cells increases after
their absorption
They are transported into capillaries by
GLUT2 down their concentration gradient

40. Monosaccharides released from intestinal
mucosa into capillaries enter portal veins
Their first destination is liver
All pathways of carbohydrate metabolism
are present in liver
Glucose and galactose/fructose can be
converted into each other in liver

41. Excess glucose can be stored in liver as
glycogen
Non-carbohydrates can be converted into
glucose in liver
Liver also releases glucose into systemic
circulation

42. All the tissues take up glucose from
circulation
For uptake of glucose, tissues require
Glucose Transporters (GLUTs)
Different tissues possess different glucose
transporters having different features

43. Trans-
porter
Location Specificity Energy
depen-
dence
Insulin
depen-
dence
SGLT 1 Luminal side of
enterocytes and renal
tubular cells
Glucose,
galactose
Yes No
GLUT 1 Erythrocytes Glucose No No
GLUT 2 Contraluminal side of
enterocytes, liver and
renal tubular cells
Glucose,
galactose,
fructose
No No
GLUT 3 Brain Glucose No No
GLUT 4 Adipocytes, muscles
and myocardium
Glucose No Yes
GLUT 5 Luminal side of
enterocytes and liver
Fructose No No
Salient features of glucose transporters

44. SGLT 1 is the only energy-dependent
transporter
GLUT 4 is the only insulin-dependent
transporter
Insulin translocates GLUT 4 from cytosol to
the cell membrane

46. Metabolic pathways for carbohydrates
EMB-RCG
The pathways for metabolism of
carbohydrates include:
• Glycolysis
• Hexose monophosphate shunt
• Glycogenesis
• Glycogenolysis
• Gluconeogenesis
• Uronic acid pathway

47. Glycolysis is the main pathway for
oxidation of glucose
The end product of glycolysis is pyruvate
or lactate
Two molecules of pyruvate/lactate are
formed from one glucose molecule
The purpose of this pathway is to
capture the energy present in glucose

48. Hexose monophosphate shunt is
another pathway for oxidation of glucose
Pentoses are formed as intermediates in
this pathway
This pathway also provides NADPH

49. Glycogenesis is the pathway for storage
of glucose as glycogen
Major sites for storage of carbohydrates
are liver and muscles
Glycogenolysis is the pathway by which
stored glycogen is broken down

50. Gluconeogenesis is a pathway by which
glucose is formed from non-carbohydrates
This pathway becomes active when dietary
carbohydrates are not available
It also becomes active when glucose
cannot be utilized e.g. in diabetes mellitus

51. Uronic acid pathway is a pathway for
synthesis of glucuronic acid from glucose
Glucuronic acid is required for some
conjugation and detoxification reactions
In some species, ascorbic acid is
synthesized by this pathway

52. There are also pathways
for metabolism of:
Galactose
Fructose
Amino sugars etc