You are on page 1of 8

[Biochemistry]

2.2 Carbohydrate
Chemistry
Metabolism
[Biochemistry] 2.2 Carbohydrate
Chemistry
and Metabolism
Dr. and
Donato
Dr. Donato

July 25, 2013

22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto


OUTLINE
I.
II.
III.
IV.
V.
VI.

CHO Chemistry
STEREOISOMERS compounds with the same formula
and attachment of atoms but with different arrangements of
the atoms in space.

CHO Chemistry
Monosaccharides
Disaccharides
Polysaccharides
Other CHO Polymers
CHO Digestion and Absorption

ENANTIOMERS stereoisomers in which one isomer is the


non-superimposable mirror image of the other.
L-isomer hydroxyl group (-OH) farthest from the
carbonyl carbon is on the LEFT.

OBJECTIVES
At the end of the lecture, the student should be able to:
1. Discuss: Overview of CHO polymers.
2. Illustrate the structure of glucose and other biologically
important sugars.
3. Recognize features of carbohydrates.
4. Discuss the features of glycosidic bonds.
5. Discuss: CHO breakdown from dietary sources.

D-isomer hydroxyl group (-OH) farthest from the


carbonyl carbon is on the RIGHT; cells prefer this
configuration.

References:
1. Devlin, T.M. Textbook of Biochemistry, 7th edition. 2011.
2. Abainza, et al. Carbohydrate Chemistry and Absorption.
Biochemistry Transcription. 2011.
3. Berg, et al. Biochemistry, 5th edition.
4. Cox, et al. Lehninger Principles of Biochemistry, 5th
edition, 2008.
5. Smith, et al. Marks Basic Medical Biochemistry: A
Clinical Approach, 2nd edition.
6. Granner, et al. Harpers Illustrated Biochemistry, 26th
edition, 2003.
7. Donato, C. Carbohydrate Chemistry and Metabolism.
Lecture. UERM Anatomy Amphitheater. July 25, 2013
Legend: Italicized quoted from the lecturer; bold
emphasis, or from references

Fig. 1: (Left) D-isomer of Glyceraldehyde; (Right) L-isomer of


Glyceraldehyde. The hydroxyl group has been boxed. Glyceraldehyde is
one of the simplest monosaccharides.

EPIMERS stereoismers which differ in the arrangement of


substituents in only one position. In monosaccharide
epimers, the position of OH distinguishes the
monosaccharide. The carboxyl group remains the same.
(e.g. Glucose and Mannose, to be discussed later in this
trans.)
Epimerase a type of enzyme responsible for
interconversion of epimers.

ALDOSE AND KETOSE:


A monosaccharide can either be an Aldose or a
Ketose based on the position of the carbonyl
carbon.
The carbonyl carbon is also known as the most
oxidized carbon.
In Fischer formula, counting of carbons starts from
the topmost carbon going down. The topmost carbon
is thus labelled Carbon 1, C1 or Position 1.
ALDOSE: carbonyl carbon is at position 1 (aldehyde
group.)
KETOSE: carbonyl carbon is at any other position
(ketone group.)

- [1 of 8] -

[BIOCHEM] 22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto

[Biochemistry] 2.2 Carbohydrate Chemistry and Metabolism Dr. Donato

Figure 4: (Left) Glucose in pyranose form. The highlighted OH represent


the positions at which Glucose and its epimers differ. (Right) Glucose in
Fischer projection. Highlighted OH represents the OH which determines
the chirality of the molecule.

Fig. 2: (Left) An example of an aldose; (Right) An example of a ketose.


Carbonyl group has been boxed.

FISCHER FORMULA linear formula which can be


depicted in the D- or L- form.
HAWORTH FORMULA the cyclic form of the Fischer
formula which can be depicted in the or form.
Furanose five-membered ring (e.g. Fructose)
Pyranose six-membered ring (e.g. Glucose); In
biological solutions, this is the most stable form of
Glucose.
The cyclic structure is a hemiacetal formed by a
reaction between the aldehyde group and a hydroxyl
group (R-O-C-OH).
During cyclization, the carbonyl carbon transforms
into a new stereocenter referred to as the anomeric
carbon.
Locate the oxygen in the ring. There would be carbon
on either side of the oxygen. The carbon with the
attached OH group is the anomeric carbon.
Depending on the position of the OH group, the
anomeric carbon can either be in the or form.
o : OH group is axial DOWN
o : OH group is axial UP

D-Galactose
- An aldohexose.
- Differs in the position of OH at C4.
- C4 is the non-reducing end.
- Can be changed to glucose in the liver and
metabolized.
- Synthesized in the mammary glands to make the
lactose of milk.
- A constituent of glycolipids and glycoproteins.

Figure 5: (Left) Galactose in pyranose form. Highlighted OH represents


the position by which it is distinguished from Glucose. (Right) Galactose in
Fischer projection.

D-Mannose
- An aldohexose
- Differs in the OH configuration at C2.
- A constituent of many glycoproteins.
Figure 3: D-glucose in Haworth projection. The position of the OH group
dictates whether it is or .

MONOSACCHARIDES
MONOSACCHARIDES simple sugars; carbohydrates that
cannot be hydrolyzed into simpler compounds.
D-Glucose
- An aldohexose.
- Has the empirical formula (C6H12O6)
- In biological solutions, pyran-D is the most stable
form of glucose (pictured below)
- Biomedically the most important monosaccharide.
- The sugar of the body. The sugar carried by the
blood, and the principal one used by tissues.

Figure 6: (Left) Mannose in pyranose form. Highlighted OH represents


the position by which it is distinguished from Glucose. (Right) Mannose in
Fischer projection.

- [2 of 8] -

[BIOCHEM] 22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto

[Biochemistry] 2.2 Carbohydrate Chemistry and Metabolism Dr. Donato


D-Fructose
- A ketohexose.
- An isomer of the three aforementioned aldohexoses.
- During metabolism, aldohexoses can be converted
into fructose in the presence of an isomerase
enzyme.
- Differs from Glucose in C1 and C2.
- Can be expressed in biological solutions either in
Fischer projection form or furanose form.
- Relatively more stable compared to glucose (Magat,
2012)
- C2 is the most oxidized carbon (reducing end)
- Can be easily phosphorylated at either C1 or C6 (e.g.
Fructose 1-6 bisphosphate.)
- Can be changed to glucose in the liver and so be
used in the body.

Figure 9: (Left) Deoxyribose in furanose form. Boxed segment represents


the reduced carbon. (Right) Deoxyribose in Fischer projection.

DISACCHARIDES
DISACCHARIDES formed when the anomeric carbon of
one sugar molecule interacts with one of several hydroxyl
groups in the other sugar molecule.
GLYCOSIDIC BONDS
o Primary structural linkage in all polymers of
monosaccharides.
o An acetal linkage in which the anomeric carbon of a
sugar is condensed with an alcohol, an amine, or a
thiol (R-O-C-O-R).
o The carbon in the acetal has a fixed or position.

Figure 7: (Left) Fructose in furanose form. Highlighted OH represents the


reducing end. (Right) Fructose in Fischer projection.

D-Ribose
- An aldopentose.
- Found in RNA.
- Structural elements of nucleic acids and coenzymes,
e.g. ATP, NAD, NADP, flavoproteins.
- Ribose phosphates are intermediates in the HMP
Shunt.

MALTOSE
- -D-glucopyranosyl-(1 4)--Dglucopyranose.(Lehninger 5/E, pg. 243)
- Composed of two -D-glucose residues linked by an
1,4-glycosidic bond.
- Present in malt, obtained from corn or grain that is
used in malted milk and brewing
- Can be broken down by the enzyme maltase.
- is a reducing sugar because there is a free hydroxyl
group on the anomeric carbon of monosaccharide B.
It can bond again to glucose.
- linear

Figure 8: (Left) Ribose in furanose form. (Right) Ribose in Fischer


projection.

D-Deoxyribose
- Reduced form of Ribose; difference is in C2.
- C2 contains H below the ring
- Found in DNA

Figure 10: Formation of Maltose between two Glucose residues. Note that
the reaction involves loss of water.

ISOMALTOSE
- -D-glucopyranpsyl-(16)--D-glucopyranose.
- Two -D-glucose residues bonded covalently with
an 1,6-glycosidic bond.
- Can be broken down by sucrase-isomaltase
complex.
- branched
- [3 of 8] -

[BIOCHEM] 22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto

[Biochemistry] 2.2 Carbohydrate Chemistry and Metabolism Dr. Donato


Table 1: Differences between lactose intolerance and galactosemia.
LACTOSE
GALACTOSEMIA
INTOLERANCE
SIGNS AND
GIT disturbance upon
GIT disturbance,
SYMPTOMS
milk ingestion,
failure to thrive,
diarrhea, flatulence
enlargement of
liver, jaundice

Figure 11: Isomaltose.

LACTOSE
- -D-galactopyranosyl-(14)--D-glucopyranose
(Lehninger 5/E, pg. 244)
- A -D-galactose and -D-Glucose bonded
covalently with a 1,4-glycosidic bond.
- Major carbohydrate in milk
- Synthesized in lactating mammary glands (females
only)
- Can be broken down by the enzyme lactase or galactosidase. (inducible enzyme)
- Enzyme depletes as the individual ages if lactose is
not maintained in the diet. This leads to lactose
intoleranceosmotic diarrhea and flatulence upon
ingestion of lactose-rich foods.
- There is now an exogenous lactase preparation to
counter lactose intolerance.

ENZYME
DEFICIENCY

lactase

Gal1PO4 Uridyl
Transferase (inherited
disease)

TREATMENT

avoid products
containing too much
milk, consumption of
milk in small amounts

remove galactose
and lactose from
the diet

SUCROSE
- -D-glucopyranosyl-(12)--D-fructofuranoside
- Formed by linkage of C1 of -D-Glucose and C2 of
-D-Fructose with a 1, 2-glycosidic bond.
- The sweetest sugar; synthesized only in plants.
- Commonly known as table sugar; obtained from
cane or beet, some fruits and vegetables
- Can be broken down by Sucrase.
- Note that the anomeric carbons of glucose and
fructose are both involved in the glycosidic bond;
hence, sucrose has no free hydroxyl group on the
anomeric carbon. Sucrose is thusly a non-reducing
sugar and will not react with Benedict solution.

Figure 13: Sucrose (fructofuranoside inverted and flipped)

POLYSACCHARIDES
POLYSACCHARIDES large polymer oligosaccharides
formed by the linkage of multiple monosaccharides. They
play vital roles in energy storage and in maintaining the
structural integrity of an organism.

Figure 12: (Above) Lactose; (Below) The monosaccharides that form


lactose.

Two types of polysaccharides:


o Homoglycan/ homopolymer/ homopolysaccharide
one type of monosaccharide
o Heteroglycan/ heteropolymer/
heteropolysaccharide more than one type of
monosaccharide
STARCH
- Storage of glucose in plant cells; found in potatoes,
legumes and other vegetables
- -Dextrin: an oligosaccharide intermediate in starch
hydrolysis; contains 1,6-glycosidic bonds and
- [4 of 8] -

[BIOCHEM] 22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto

[Biochemistry] 2.2 Carbohydrate Chemistry and Metabolism Dr. Donato


1,4-glycosidic bond.; nonsoluble fiber; important
in the health of the GI tract
- Two main constituents of starch:
o Amylose: glucose ( 1 4) glycosidic bonds;
linear
o Amylopectin: branched version of amylose
which has one 1,6-glycosidic bond for every
24-30 1,4-glycosidic bond. (Harper 26/E, pg.
107)
- Both are rapidly hydrolyzed by salivary and
pancreatic -Amylase. (Stryer, 5/E)
Figure 15: A comparison amylose, amylopectin and glycogen structure
.

OVERVIEW OF OTHER CARBOHYDRATE POLYMERS


GLYCOLIPIDS
- Involved in intracellular communication.
- Component of cell membranes.
- Specific sites for cell recognition.
- Found in brain and neurons, which help in nerve
conduction and myelin formation

Figure 16: Glycolipid structure.

Figure 14: Starch structure. (A) Amylose, showing helical coil structure. (B)
Amylopectin, showing 1,6-glycosidic linkage.

CELLULOSE
- Polysaccharide that serves a structural role; found in
the cell walls of plants
- Formed by 1,4-glycosidic bonds.
- there is no enzyme for cellulose in the human body;
insoluble

GLYCOPROTEINS
- Structure: CHO + Serine, Threonine, Asparagine
- Found in the cell membrane, extracellular matrix and
in the blood.
- Components of antibodies and hormones
- e.g. Antigens on the cell membrane for ABO blood
typing.

GLYCOGEN
- Main storage of glucose in animal cells
- It is composed of one 1,6-glycosidic bonds for
every 8-12 1,4-glycosidic bond.
- More highly branched and compact than
amylopectin.

Figure 17: Diagram showing the carbohydrate chains that determine the
ABO blood group.

- [5 of 8] -

[BIOCHEM] 22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto

[Biochemistry] 2.2 Carbohydrate Chemistry and Metabolism Dr. Donato


CARBOHYDRATE DIGESTION AND ABSORPTION
Monosaccharides are directly absorbed.
Disaccharides require enzymes of the small intestinal
surface for hydrolysis into monosaccharides.
Polysaccharides depend on pancreatic amylase and
intestinal surface enzymes for digestion.
Hydration occurs during heating and is essential for
efficient absorption.
Units other than monosaccharides cannot be absorbed
without being hydrolysed.
Different carbohydrates are digested at different rates;
glycemic index indicates how rapidly a carbohydrate
causes an increase in blood glucose levels.
Generally, blood glucose levels rise 30-60 minutes after
eating.
Glucose then rapidly enters cells from the blood. Within
two hours of a meal in normal persons, blood glucose
levels drop to baseline levels.
DIGESTION
Salivary and Pancreatic -amylase
o Hydrolyze internal 1,4-bonds at random intervals.
o Starch is hydrolyzed by salivary and pancreatic
amylase into maltose and isomaltose derivatives.
o Maltose and isomaltose broken down by maltase and
isomaltase in the intestine.
o Final product is glucose.
Digestion in the Colon
o Previously undigested starches get digested by
colonic bacteria, producing gases (i.e. H2, CO2,
CH4), short chain fatty acids (i.e. Acetic Acid,
Propionic Acid, Butyric Acid), and lactate.
ABSORPTION
MONOSACCHARIDE TRANSPORTERS:
Na+-Dependent Transporters (SGLT)
o Active uptake of glucose against a concentration
gradient.
o SGLT1 and SGLT2 are located at the luminal side of
the cells; mediate active uptake of D-Glucose and DGalactose.
o Na+-K+-ATPase on serosal side maintains low
concentration of Na+ inside the cell.
o Influx of Na+ from the luminal side along the
concentration gradient pulls sugar with it. Hence,
SGLT is a cotransporter.
o The greater the Na+ gradient, the more glucose
enters; and if Na+ in extracellular fluid is low, glucose
transport stops.

Figure 18: The transcellular movement of glucose in an intestinal cell.


+
Glucose follows Na across the luminal epithelial membrane. The Na+
gradient that drives this symport is established by Na+ -K+ exchange,
which occurs at the basal membrane facing the extracellular fluid
compartment via the action of the Na+ -K+ -ATPase. Glucose at high
concentration within the cell moves "downhill" into the extracellular fluid
by facilitated diffusion (a uniport mechanism), via GLUT2. (Harper)

GLUT 1:
o High-affinity glucose transport system
o Found in all cells; more expressed in cell types with
barrier functions.
o Glucose transporter of RBCs.
o Exhibits specificity for glucose and related Dhexoses.
GLUT 2:
o High-capacity, low-affinity transporter
o Found in liver, pancreatic cells, small intestine
and kidneys; contraluminal side of enterocytes.
o In liver, facilitiates outward transport of glucose
when liver glycogen is broken down to meet
physiological needs.
o Is signaled by insulin for storage as glycogen or
conversion to fat.
o All three monosaccharides (glucose, galactose,
fructose) are transported from the intestinal mucosal
cell into the portal circulation.
GLUT 3:
o High-affinity glucose transport system
o Found in the brain (neurons), kidneys, placenta
o Major transporter in the CNS
o Transport D-sugars and glycerol.
GLUT 4:
o High-affinity, insulin-dependent transporter
o Found in cardiac and skeletal muscle, adipose
tissue
o When not activated by insulin, GLUT4 are contained
in vesicles near the membrane of the cell.
o Once insulin binds to its receptor a signalling pathway
initiates the migration of GLUT 4 to the cell
membrane, leading to an increase in GLUT4
transpoters.
o Can also increase in amount with exercise.
o Transport D-sugars and glycerol

- [6 of 8] -

[BIOCHEM] 22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto

[Biochemistry] 2.2 Carbohydrate Chemistry and Metabolism Dr. Donato


Lactase: most commonly deficient enzyme
Deficiency results in milk intolerance.
Lack of lactose hydrolysis in the small intestine =
inability to absorb lactose, bacterial fermentation
Bacterial fermentation produces gas and
osmotically active solutes (draws water into
intestinal lumen: diarrhea)

GLUT 5:
o Fructose transporter
o Found in small intestine. Testes and sperm cells also
prefer fructose.
o High-fructose dietary sources are very high in calories
because it can be oxidized on its own and it has its
own transporter.

COMPETENCIES:
1.) Given a normal newborn, identify biochemical pathways
or processes of carbohydrates that are involved to
achieve normal growth and development.
Glycolysis - the oxidation metabolism of glucose
molecules to obtain ATP and pyruvate
o Pyruvate from glycolysis enters the Krebs
cycle, also known as the citric acid cycle, in
aerobic organisms after moving through
pyruvate dehydrogenase complex.
The pentose phosphate pathway, which acts in
the conversion of hexoses into pentoses and in
NADPH regeneration.
Glycogenesis - the conversion of excess glucose
into glycogen as a cellular storage mechanism; this
prevents excessive osmotic pressure buildup inside
the cell
Glycogenolysis - the breakdown of glycogen into
glucose, which provides a glucose supply for
glucose-dependent tissues.
Gluconeogenesis - de novo synthesis of glucose
molecules from simple organic compounds. An
example in humans is the conversion of a few
amino acids in cellular protein to glucose.

Figure 19: Carbohydrate absorption and monosaccharide transporters.

Intercellular spaces are nearly absent because of tight


junctions between cells. Basement membrane is also
intact and continuous.
GLUTs are the only way for glucose to enter the brain
through the cerebrospinal fluid (CSF).
By contrast, basement membrane in non-neural
tissues is not continuous, tight junctions are not
present; glucose can enter through GLUT, in between
cells and can also be influenced by rate of pinocytosis.
Therefore, the rate of absorption in neural tissues is
less than the rate of absorption in non-neural
tissues.

2.) Apply the biochemical concepts and principles that will


help explain the growth and development of the
newborn from birth onwards.
Glucose is the most important carbohydrate; most
dietary carbohydrate is absorbed into the
bloodstream as glucose formed by hydrolysis of
dietary starch and disaccharides, and other sugars
are converted to glucose in the liver. Glucose is the
major metabolic fuel of most mammals and a
universal fuel of the fetus. It is the precursor for
synthesis of all the other carbohydrates in the body,
including glycogen for storage; ribose and
deoxyribose in nucleic acids; galactose in lactose
of milk, in glycolipids, and in combination with
protein in glycoproteins and proteoglycans.
(Harper)

Table 2: Sources of dietary carbohydrates.

DIETARY CARBOHYDRATES
Carbohydrate
Source
Fructose
Fruits, honey
Glucose
Fruits, honey, grape
Amylopectin
Potatoes, rice, corn, bread
Amylose
Potatoes, rice, corn, bread
Sucrose
Table sugar, desserts
Trehalose
Young mushrooms
Lactose
Milk, milk products
Raffinose
Leguminous seeds

3.) Correlate the biochemical or molecular basis with the


growth and development of the infant.

CLINICAL CORRELATION
DISACCHARIDASE DEFICIENCY
Present in one or more enzymes due to genetic
defects, physiological decline with age or injuries to
mucosa.

Glucose main metabolic fuel for tissues; blood


sugar; obligatory energy substrate of the brain.
Fructose readily metabolized by the body;
metabolism may lead to glycogen and triglyceride
synthesis.
Galactose derived from hydrolysis of lactose;
readily metabolized to glucose, synthesized in the

- [7 of 8] -

[BIOCHEM] 22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto

[Biochemistry] 2.2 Carbohydrate Chemistry and Metabolism Dr. Donato

mammary gland for synthesis of lactose in milk; a


constituent of glycolipids, and glycoproteins.
Mannose constituent of glycoproteins.
Ribose structural component of nucleic acids and
coenzymes, including ATP, NAD(P), and flavincoenzymes.
D-Glucosamine constituent of hyaluronic acid
D-Galactoseme also known as chondrosamine;
constituent of chondroitin.
Glycogen storage polysaccharide in animals
Glycosaminoglycans (mucopolysaccharides) are
complex carbohydrates containing amino sugars
and uronic acids. They may be attached to a
protein molecule to form a proteoglycan.
Proteoglycans provide the ground or packing
substance of connective tissue. They hold large
quantities of water and occupy space, thus
cushioning or lubricating other structures, because
of the large number of OH groups and negative
charges on the molecule which, by repulsion, keep
the carbohydrate chains apart. Examples are
hyaluronic acid, chondroitin sulfate, and
Hyeparin
Glycoproteins (also known as mucoproteins) are
proteins containing branched or unbranched
oligosaccharide Cains; they occur in cell
membranes and many other situations; serum
albumin is a glycoprotein. The sialic acids are Nor O- acyl derivatives of neuraminic acid
peuraminic acid is a nine-carbon sugar derived
from mannosamine (an epimer of glucosamine) and
pyruvate.
Sialic acids are constituents of both glycoproteins
and gangliosides.

- [8 of 8] -

[BIOCHEM] 22 Indiongco, Hernandez, Hing, Hitosis, Hiwatig, Ibero, Improgo, Jacinto