Carbohydrate

Karthika Paul
Asst. Prof
Vivekananda College of pharmacy
Bangalore

Carbohydrate
Mainly sugars and starches, together constituting one of
the three principal types of nutrients used as energy
sources (calories) by the body. Carbohydrates can also
be defined chemically as neutral compounds of
carbon, hydrogen and oxygen. Carbohydrates come in
simple forms such as sugars and in complex forms
such as starches and fibers. The body breaks down
most sugars and starches into glucose, a
simple sugar that the body can use to feed its cells.
Complex carbohydrates are derived from plants.
Dietary intake of complex carbohydrates can lower
blood when they are substituted for saturated fat.

Definition
Carbohydrates are the organic compounds consists of
polyhydroxy aldehyde or ketone containing carbon,
hydrogen, oxygen which on hydrolysis gives the free aldehyde
or ketonic group.
General formula: C6H12O6
Source : are found in a wide array of both healthy and
unhealthy foods bread, beans, milk, popcorn, potatoes,
cookies, spaghetti, soft drinks, corn, and cherry pie. They
also come in a variety of forms. The most common and
abundant forms are sugars, fibers, and starches.

1. Monosaccharides:
i. These are simplest of carbohydrates and are known as
sugars.
ii. These are the building units of complex carbohydrates.
iii. These cannot be hydrolyzed.
iv. These are sweet-tasting, crystalline and soluble in water.
v. They have a potential aldehyde or keto group and hence,
are reducing in nature.
vi. Aldehyde group or the reducing centre always lies at C No.
1 of the monosaccharide molecule. Such sugars are known
as aldoses or aldose sugars.
vii. Monosaccharide’s having keto group are known as
ketoses or ketose sugars. In such sugars the keto group or
the reducing centre always lies at C No. 2.

Depending upon the number of the C atoms, the
monosaccharide’s are further classified as follows:
(i) Triose Sugars, C3H6O3 (e.g., glyceraldehyde,
dihydroxyaeetone)
(ii) Tetrose Sugars, C4H8O4 (e.g., erythrose)
(iii) Pentose Sugars, C5H10O5 (e.g., ribose, ribulose,
xylose, xylulose, arabinose).
(iv) Hexose Sugars, C6H12O6 (e.g., glucose, fructose,
galactose mannose).
(v) Heptose Sugars, C7H14O7 (e.g., sedoheptulose).

2. Oligosaccharides:
i. These consist of more than one but fewer number of
monosaccharide molecules joined together by glycosidic
bonds.
ii. On hydrolysis, they yield the monosaccharide units which
may be similar or dissimilar.
iii. These are also sweet tasting, crystalline, soluble sugars.
iv. These may or may not have a free -OH group at the
reducing centre and accordingly may or may not be
reducing.
The oligosaccharides are grouped in following categories:
(i) Disaccharides. C12H22O11 (e.g., sucrose, maltose, lactose
etc.)
(ii) Trisaccharides, C18H32O16 (e.g., raffinose, gentianose etc.)

3. Polysaccharides:
i. These consist of a large number of (often thousands)
monosaccharide units to form branched or un-
branched chains.
ii. These can be hydrolysed to yield monosaccharide
units which are usually similar.
iii. These are usually amorphous, tasteless, non-sugars
and insoluble in water.
Polysaccharides can be grouped into two categories:
(i) Structural Polysaccharides (e.g., cellulose, hemi-
cellulose, pectic substances, chitin, gum, mucilage
etc.)
(ii) Storage Polysaccharides (e.g., starch, inulin, glycogen
etc.)

Absorption of Monosaccharides
1- Simple Diffusion
According to concentration gradient.
Fructose & pentoses.
2- Facilitated Transport
GLUT5: glucose, galactose & fructose.
3- Active Transport
Sodium glucose transporter (SGLT)I: glucose &
galactose.

Fate of Absorbed Sugars
Absorbed Fructose and galactose enters liver and
glucose uptaken by tissues
Pathways for glucose utilization
1- Oxidation for production of energy
2- Provides other compounds: Carbohydrates: i.e.
fructose, galactose & pentoses. Glycerol 3-
phosphate: triacylglycerol and phospholipids ,
Acetyl CoA: cholesterol and fatty acids Non
essential amino acids.
3- Storage: glycogen in liver & triacylglycerol in
adipose tissue.
4- Excretion in urine.

Glycolysis
The glycolytic pathway is a major metabolic pathway for
microbial fermentation which involves the catabolism
of glucose into pyruvate.
It is also called the Embden–Meyerhof–Parnas
pathway for its major discoverers.
Regardless of whether glucose is fermented or respired,
it travels through this pathway thus it is referred to as
the universal pathway of glucose catabolism.
Glycolysis takes place in the cytoplasm of cells in most
body tissues.

Steps involved in glycolysis
In glycolysis, a molecule of glucose is degraded in a
series of enzyme catalyzed reactions to yield two
molecules of the carbon compound – pyruvate.
The fermentation of glucose through the glycolytic
pathway can be divided into two stages, each requiring
several independent enzymatic reactions.
Phase I comprises of “preparatory” reactions : These are
not redox reactions and do not release energy but
instead form a key intermediate of the pathway.
In Stage II, redox reactions occur, energy is conserved,
and two molecules of pyruvate are formed.

Phase I Energy Investment stage / Preparatory phase
1. Glucose is phosphorylated with the use of ATP by
hexokinase, yielding glucose 6-phosphate.
2. Glucose 6-phosphate is then isomerized to fructose 6-
phosphate by phosphoglucose isomerase.
3. Second phosphorylation leads to the production of
fructose1,6-bisphosphate by phosphofructokinase 1 (PFK-
1), which is the rate-limiting enzyme of glycolysis. The
reaction uses 1 ATP.
Phase II splitting stage / phase
4. The enzyme aldolase then splits fructose 1,6-bisphosphate
into two 3-carbon molecules, glyceraldehyde 3-phosphate
and its isomer, dihydroxyacetone phosphate, which is
ultimately converted into glyceraldehyde 3-phosphate.

Phase III: Energy production phase (Pay-off phase)
5.The first redox reaction is the oxidation of glyceraldehyde 3-
phosphate to 1,3 bisphosphoglyceric acid by glyceraldehyde
3-phosphate dehydrogenase using NAD + as a cofactor.
6.1, 3-bisphosphoglyceric acid is converted to 3-
phosphoglyceric acid by phosphoglycerate kinase. This
reaction generates 2 ATP per glucose molecule.
7.Reversible conversion of 3-phosphoglyceric acid to 2-
phosphoglyceric acid by phosphoglycerate mutase.
8.Reversible conversion of 2-phosphoglycerate to
phosphoenolpyruvate (PEP) by enolase.
9.Regulated, irreversible reaction involving the conversion of
PEP to pyruvate by pyruvate kinase. There is a net gain of 2
ATP per glucose molecule in this reaction.

ATP PRODUCTION/ BIOENERGETICS :
During Stages I and II of glycolysis, two ATP molecules
are consumed and four ATP molecules are
synthesized.
Thus, the net energy yield in glycolysis is two
molecules of ATP per molecule of glucose fermented.

Significance of Glycolysis Pathway:
The glycolytic pathway is employed by all tissues for the
breakdown of glucose to provide energy in the form of ATP.
Important pathway for the production of energy especially
under anaerobic conditions.
It is crucial for generation of energy in cells without
mitochondria.
It forms products that are intermediates for other metabolic
pathways.
Glycolysis interfaces with glycogen metabolism, the pentose
phosphate pathway, the formation of amino sugars,
triglyceride synthesis (by means of glycerol 3-phosphate),
the production of lactate (a dead-end reaction), and
transamination with alanine.

Importance of Intermediates
Pyruvate: active acetate, oxaloacetate, and lactate.
DHAP glycerol 3-phosphate which is used in
triacylglycerol and phospholipid synthesis.
Non essential Amino acids :
Pyruvate → alanine
3-Phosphoglycerate → serine.
Regulatory factors:
Key enzymes: GK, PFK, PK
Stimulated by: insulin, AMP, F6P
Inhibited by: glucagon, ATP, citrate

GLUCONEOGENESIS
It is the synthesis of glucose and /or glycogen from non-
carbohydrate sources.
Site: Liver, kidney.
Steps: reversal of glycolysis, the irreversible reactions are
reversed by 4 enzymes:
Glycolytic Key Enzymes Gluconeogenic Key Enzymes
Glucokinase Glucose 6-phosphatase
Phosphofructokinase-1 Fructose 1,6-bisphosphatase
Pyruvate kinase Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase.

Sources
1.Lactate.
2.Pyruvate.
3.Glucogenic amino acid
4. Glycerol
5.Odd chain FA
Regulation
Insulin: ↑↓ gluconeogenesis,↑↑ glycolysis
Anti-insulin:↑↑ gluconeogenesis, ↓↓glycolysis
Importance
Source of blood glucose during fasting & starvation.
Removal of waste products e.g. lactate, glycerol.

Gluconeogenesis is define as a metabolic pathway of
synthesizing new glucose molecules from the non-
glucose substrates like lactate, TCA intermediates etc.
Sometimes, it also refers as “Endogenous glucose
pathway” as it needs an input of energy. It is
an anabolic process, where the small precursor’s
molecules combine to produce a high energy product
like glucose. Gluconeogenesis is an important cycle, as
glucose is a “Key metabolite” to carry out all catabolic
processes and to sustain life.
Site of Occurrence
The process of neoglucogenesis takes place inside the
liver, cortex of kidney and enterocyte cells of the small
intestine. Most of the steps in gluconeogenesis occur
inside the cytosol than in mitochondria.

Three Irreversible Steps of Gluconeogenesis
Gluconeogenesis differs from glycolysis by three
irreversible reactions, mediated by three different
enzymes.
Step-1: Conversion of pyruvate into phosphoenolpyruvate
It is the first reaction that bypasses an irreversible reaction
of glycolysis, mediated by pyruvate kinase. The
transformation of pyruvate into phosphoenolpyruvate
includes two series of steps like:

Step 2: Carboxylation of pyruvate into oxaloacetate
Pyruvate carboxylase mediates the transformation of pyruvate to
oxaloacetate by adding one carbon-dioxide molecule. This enzyme was
first discovered in the year 1960, by a scientist named Merton Utter.
Pyruvate carboxylase is a mitochondrial enzyme, which helps pyruvate
present in the cytosol to enter into the mitochondrial matrix through
the help of MPC-1 and MPC-2 complexes. The carboxylation of
pyruvate into oxaloacetate requires the use of high
energy ATP molecule and the presence of Mg2+ and Mn2+ ions. As a
result of pyruvate carboxylation, oxaloacetate and one ADP molecule
produce.
Step 3: Decarboxylation of oxaloacetate into Phosphoenolpyruvate
The transport of oxaloacetate from mitochondria to cytosol does not
involve any carrier complex or transporters. It only occurs by
the reduction of oxaloacetate into malate via mitochondrial malate
dehydrogenase. Malate then moves beyond the inner mitochondrial
membrane through the malate aspartate shuttle by the help of malate
α-ketoglutarate transporter. In a cytosol, malate reoxidizes
into oxaloacetate by an enzyme (cytosolic malate dehydrogenase).

Substrates
All the intermediates of glycolysis and tricarboxylic acid cycle provide a
substrate for the neoglucogenesis. Substrates like glycerol, lactate,
glucogenic amino acid etc.
Glycerol:It is a product formed as a result of triglyceride hydrolysis in
the adipose tissue and transferred to the liver via blood. Glycerol is an
intermediate which can produce glucose solely in the cytosol. It enters
the cycle by two sequential steps:

Lactate (Cori’s cycle)
It is a product formed as a result of anaerobic glycolysis in skeletal
muscles and erythrocytes. Lactate is transferred from muscle to the
liver via blood. It reconverts into pyruvate inside a liver, and later
undertake the production of glucose through gluconeogenesis.

Glucogenic amino acids
These are derived by the hydrolysis of tissue proteins. Glucogenic acids
like α-ketoglutarate, Succinyl Co-A, fumarate, oxaloacetate and
fumarate are the only precursors which can produce glucose. There are
two entry points, namely pyruvate and oxaloacetate, through which
the glucogenic amino acids can enter the cycle of neoglucogenesis.

Importance
1.The gluconeogenesis cycle performs a crucial role
in blood-glucose homeostasis, during starvation.
2.Glucose produced in this cycle fulfils the energy
demands of many cells and tissues like RBCs, neurons,
skeletal muscle, medulla of the kidney, testes,
embryonic tissue etc.
3.Neoglucogenesis cycle clears metabolites accumulated
in the blood, like lactate (produced from muscles and
RBCs) and glycerol (produced from adipose tissue) etc.

Regulation
The regulation of gluconeogenesis includes the following factors:
Acetyl CoA
It is a kind of reciprocal regulation, which regulates the
transformation of pyruvate to PEP. Acetyl Co-A cumulates in the
liver as a result of excessive lipolysis of adipose tissue. When its
concentration is more, it inhibits the activity of glycolytic
enzyme “Phosphate dehydrogenase” and stimulates the
activity of pyruvate carboxylase. Thus the high level of acetyl Co-
A influences the gluconeogenesis cycle. It can regulate the
pathway both positively and negatively.
Positive regulation: Acetyl Co-A promotes the enzymatic activity
by the pyruvate carboxylase, which in turn produce more
oxaloacetate and end product glucose.
Negative regulation: Acetyl Co-A inhibits the enzymatic activity
of pyruvate dehydrogenase, which function is to convert
pyruvate carboxylase to acetyl Co-A.

Glucagon
It is a kind of hormonal regulation that is secreted from the α-cells of
pancreatic islets when the blood glucose level in a body starts
decreasing. Glucagon regulates the conversion of fructose 1, 6-
biphosphate to fructose 6-phosphate or favours the process of
gluconeogenesis by the following two mechanisms:
Glucagon mediates cyclic AMP that can convert the pyruvate kinase to an
inactive form, which results in a decrease in the conversion of PEP to
pyruvate. Finally, it diverts the cycle for the synthesis of glucose.
Secondly, glucagon reduces the concentration of fructose 2, 6-
phosphate that inhibits the enzymatic activity of
phosphofructokinase and activates fructose 1, 6-biphosphate to
promote glucose synthesis.
Glucogenic amino acids
It is a kind of substrate-level regulation, which regulates the
conversion of glucose 6-phosphate into glucose. Substrates like
glucogenic acid influence the process of neoglucogenesis at the time of
decreased insulin level. When the concentration of insulin decreases,
the muscle protein metabolizes into the amino acids for the purpose
of gluconeogenesis.

Glycogen Metabolism
1.Glycogenesis
Definition: synthesis of glycogen from glucose.
Site: cytosol of liver & muscles.

Glycogenolysis
Definition: breakdown of glycogen to glucose in liver or G6P
in muscles ( due to absence of G6 phosphatase in muscles).
Importance:
In muscles: source of energy during exercise.
In liver: source of blood glucose during 18 hours starvation

Hexose Monophosphate Pathway (HMP)
Alternative route for glucose oxidation not for energy
production.
Site: cytosol of liver, adipose tissue, ovaries, testes, RBCs
& retina.
Steps:
Oxidative irreversible phase:
Glucose 6-phosphate undergoes dehydrogenation &
decarboxylation to yield ribulose 5-phosphate.
Nonoxidative reversible phase:
6 molecules of ribulose 5-P are converted to 5
molecules of glucose 6-P by two enzymes:
transketolase & transaldolase.

Importance of HMP pathway
I. It provides ribose 5-phosphate required for synthesis
of nucleotides and nucleic acids.
II- Main source of NADPH, required for:
A) Reductases: eg.Glutathione reductase

2. Folate, retinal reducatase
3.Reducatases of FA, steroid synthesis.
B)Hydroxylases e.g. Steroids hydroxylase
C) NADPH Oxidase: phagocytosi(respiratory burst).

Favism
Genetic deficiency of glucose-6-phosphate dehydrogenase
(G6PD).
Precipitating factors: Certain drugs (premaquine, aspirin),
Fava beans
Symptoms:
Asymptomatic: in between attacks. Hemolytic crisis: on
exposure to above factors.
Mechanism:
G6PD deficiency → HMP inhibition →↓ NADPH →
Inhibition of glutathione reductase → ↓ reduced glutathione
→failure to protect cells from oxidative damage by
H2O2 →Lysis of red cells → hemolytic anemia, jaundice.
Managment:
Avoid drugs, fava beans.
Blood transfusion during attacks

Uronic acid Pathway
is an alternative route for glucose oxidation.
Site: cytosol of liver
Importance of Uronic acid pathway:
Main function is formation of UDP-glucuronate: 1-
Glycosaminoglycans (GAGs) synthesis.
2- Synthesis of L-ascorbic acid (not in human)
3- Conjugation reactions: with bilirubin, steroids to
make them: more soluble, easily excreted i.e.
Detoxication.

Hormonal regulation of blood glucose

Carbohydrate

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