Tishk International University

Faculty of Pharmacy
2nd Grade

Carbohydrate Metabolism

Asst. Lect. : Amani Tahsin

Contact Info: amani.tahsin@ishik.edu.iq
Objectives

 Chemistry of carbohydrates
 Functions of carbohydrates

 Digestion and absorption of Carbohydrates

 Glycolysis
 Gluconeogenesis

 Glycogen Metabolism (Glycogenolysis and glycogenesis)

 Pentose phosphate pathway
Introduction

Carbohydrates are the most abundant macromolecules in nature.

They are the main source and storage of energy in the body. They serve also as structural component of
cell membrane.

The general molecular formula of carbohydrate is CnH2nOn or (CH2O)n. Chemically, they

contain the elements Carbon, hydrogen and oxygen. Thus they are Carbon compounds that

contain large quantities of Hydroxyl groups.

 Carbohydrates in general are polyhydroxy aldehydes or ketones or compounds which give

these substances on hydrolysis.

Chemistry of Carbohydrates

Classification and Structure

Classification
There are three major classes of
carbohydrates
• Monosaccharides (Greek, mono = one)
• Oligosaccharides (Greek, oligo= few) 3-10 monosaccharide
units.
• Polysaccharides (Greek, Poly = many) >10 monosaccharide
units.
Functions of Carbohydrates

Carbohydrates have a wide range of functions.

1) They provide energy; act as storage molecules of energy.

2) Serve as cell membrane components and mediate some forms of

communication between cells.

* Absence of a single enzyme like lactase causes discomfort and diarrhea.

*The failure of Galactose and fructose metabolism due to deficient enzymes leads
to turbidity of lens proteins (Cataract).

* Blood glucose is controlled by different hormones and metabolic processes.

People suffer from Diabetes if the insulin hormone is less or not functioning well,
such people are prone to atherosclerosis, vascular diseases, and renal failure.
Digestion and absorption of Carbohydrates
Dietary carbohydrates principally consist of the polysaccharides: starch and glycogen. It also contains disaccharides:
sucrose, lactose, maltose and in small amounts monosaccharides like fructose and pentoses. Liquid food materials like
milk, soup, fruit juice escape digestion in mouth as they are swallowed, but solid foodstuffs are masticated thoroughly
before they are swallowed.

1 Digestion in Mouth
Digestion of carbohydrates starts at the mouth, where they come in contact with saliva during mastication.
Saliva contains a carbohydrate splitting enzyme called salivary amylase (ptyalin).

Action of ptyalin (salivary amylase).

It is α - amylase, requires Cl- ion for activation and optimum pH 6-7. The enzyme hydrolyzes α(1,4) glycosidic linkage at
random, from molecules like starch, glycogen and dextrins, producing smaller molecules maltose, glucose and
disaccharides maltotriose. Ptyalin action stops in stomach when pH falls to 3.0

Starch or glycogen α -Amylase Glucose, Maltose And Maltotriose

2 Digestion in Stomach

No carbohydrate splitting enzymes are

available in gastric juice. HCl may hydrolyze
some dietary sucrose to equal amounts of
glucose and fructose.

3 Digestion in Duodenum
Food reaches the duodenum from stomach where it meets
the pancreatic juice. Pancreatic juice contains a
carbohydrate-splitting enzyme pancreatic amylase.
Action of pancreatic Amylase

It is also an α - amylase, optimum pH 7.1. Like ptyalin it also requires Cl- for activity. The enzyme hydrolyzes
α-(1,4) glycosidic linkage situated well inside polysaccharide molecule. Other criteria and end products of
action are similar of ptyalin.

Digestion in Small Intestine

Action of Intestinal Juice

a. pancreatic amylase: It hydrolyzes terminal α-(1,4), glycosidic linkage in polysaccharides and

Oligosaccharide molecules liberating free glucose molecules.

b. Lactase : It is a β- glycosidase, its pH range is 5.4 to 6.0. Lactose is hydrolyzed to glucose and galactose.

Lactose lactase Glucose + Galactose

C. Maltase : The enzyme hydrolyzes the α -(1,4) glycosidic linkage between glucose units in maltose
molecule liberating two glucose molecules. Its pH range is 5.8 to 6.2.

Maltose maltase Glucose + Glucose

D. Sucrase : PH ranges 5.0 to 7.0. It hydrolyzes sucrose molecule to form glucose and fructose.

Sucrose Sucrase Glucose + fructose

Absorption of Carbohydrates

Products of digestion of dietary carbohydrates are practically

completely absorbed almost entirely from the small intestine.

Absorption from proximal jejunum is three times grater than that of

distal ileum. It is also proved that some disaccharides, which escape
digestion, may enter the cells of the intestinal lumen by
“pinocytosis” and are hydrolyzed within these cells.

No carbohydrates higher than the monosaccharide can be

absorbed directly in to the blood stream.
Mechanism of Absorption:
Two mechanisms are involved;

1 Simple Diffusion 2 “Active “Transport Mechanisms

This is dependent on sugar
concentration gradients  Glucose and galactose are absorbed very rapidly and
between the intestinal lumen. hence it has been suggested that they are absorbed
Mucosal cells and blood actively and it requires energy.
plasma. All the
monosaccharides are probably  Fructose absorption is also rapid but not so much as
absorbed to some extent by compared to glucose and galactose but it is definitely
simple ‘passive’ diffusion. faster than pentoses. Hence fructose is not absorbed by
simple diffusion alone and it is suggested that some
mechanism facilitates its transport, called as” facilitated
transport”
Glycolysis

Oxidation of glucose or glycogen to pyruvate

and lactate is called glycolysis.

It occurs virtually in all tissues. Erythrocytes

and nervous tissues derive its energy mainly
form glycolysis. This pathway is unique in the
sense that it can utilize O2 if available
(‘aerobic’) and it can function in absence of
O2 also (‘anaerobic’)

1 Aerobic Phase 2 Anaerobic Phase

Aerobic phase includes the This phase includes the
conversion of glucose to conversion of Glucose to
pyruvate. Oxidation is carried out lactate. NADH cannot be
by dehydrogenation and oxidized, so no ATP is
reducing equivalent is produced in electron
transferred to NAD. NADH + H+ transport chain. But the NADH
in presence of O2 is oxidized in is oxidized to NAD+ by
electron- transport chain conversion of pyruvate to
producing ATP. Lactate, without producing
ATP.
Glycolysis reactions
Stages of Glycolysis

• Investment of 2 ATP

• Production of 2
Glyceraldehyde-3-P (GAP)

• The two highly regulated

steps are hexokinase and
phosphofructokinase 1 (both
respond directly or indirectly to
energy charge).
Cont.

• Reducing power is captured

in the form of NADH; this is a
critical step.

• Phosphoglycerate kinase
and pyruvate kinase catalyze a
substrate level
phosphorylation reaction
yielding 4 ATP (2 net ATP).

• The two pyruvate molecules

are further metabolized.
During strenuous exercise,

 Oxygen in the muscles is depleted.

 Anaerobic conditions are produced.
 Lactate accumulates. OH
│
C6H12O6 + 2ADP + 2Pi 2CH3–CH–COO- + 2ATP
glucose lactate
 Muscles tire and become painful.
 After exercise, a person breathes heavily to repay the oxygen debt and reform pyruvate in the liver.
Fermentation

• Occurs in anaerobic microorganisms such as yeast.

• De-carboxylates pyruvate to acetaldehyde, which is reduced to ethanol.
• Regenerates NAD+ to continue glycolysis.
O OH
|| |
CH3—C—COO- + NADH + H+ CH3—CH2 + NAD+ + CO2

pyruvate ethanol
Disorders of Glycolysis

1) Pyruvate Kinase Deficiency

 Genetic deficiency of PK in RBCs leads to hemolytic anemia.
2) Hexokinase Deficiency
3) Lactic Acidosis
 It’s the accumulation of lactic acid in the blood.
 Gluconeogenesis

• Net synthesis or formation of glucose from non-carbohydrate

substrates is termed gluconeogenesis.

• Various amino acids, lactate, pyruvate, propionate and glycerol

are sources of carbon for the pathway.

• Gluconeogenesis meets the needs of the body for glucose when

sufficient carbohydrate is not available from the diet or glycogen
reserves.

• A supply of glucose is necessary especially for the nervous system

and erythrocytes.

• Failure of gluconeogenesis is usually fatal.

 Cont.

• Gluconeogenesis occurs mainly in liver.

• GNG occurs to a more limited extent in kidney & small intestine under some conditions.

General Features:

 Tissues:

 Liver (80%)

 Kidneys (20 %)

 Subcellular location of enzymes:

 Pyruvate carboxylase: mitochondrial

 Glucoe – 6- phosphatase : ER

 All other enzymes : Cytoplasmic

Glycogen Metabolism: Glycogen is the major storage form of carbohydrate in animals .It is mainly stored in
liver and muscles and is mobilized as glucose whenever body tissues require.

Degradation of Glycogen (glycogenolysis)

1 Shortening of chains

2 Removal of Branches

3 Lysosomal Degradation of Glycogen

3
Step 1: Action of Glycogen Phosphorylase:

Step 2: Action of Debranching Enzyme:

Step 3: Formation of Glucose-6-Phosphate

and Glucose:
Synthesis of Glycogen (Glycogenesis)

 The storage form of glucose, occurs after a meal.

 Requires a set of three reactions

(1st and 2nd are preparatory and in 3rd there is
chain elongation):

1. Synthesis of glucose-1-phosphate (G1P)

from glucose-6-phosphate by phosphoglucomutase.
2. Synthesis of UDP-glucose from G1P by
UDP-glucose phosphorylase.

2. Synthesis of Glycogen from UDP-glucose.

Requires Glycogen synthase to grow the chain
 Glycogen storage diseases
 These are a group of genetic diseases that
result from a defect in an enzyme required
for either glycogen synthesis or degradation.

 They result in either formation of glycogen

that has an abnormal structure or the
accumulation of excessive amounts of
normal glycogen in specific tissues,

 A particular enzyme may be defective in a

single tissue such as the liver or the defect
may be more generalized, affecting muscle,
kidney, intestine and myocardium.

 The severity of the diseases may range from fatal in

infancy to mild disorders that are not life threatening
some of the more prevalent glycogen storage diseases
are the following.
 Table of Glycogen Storage Diseases
Type: Name Enzyme affected Primary organ Manifestations

Type 0 glycogen Liver Hypoglycemia

1
synthase and early death
Type Ia: von Glucose-6- Liver hepatomegaly,
Gierke's phosphatase kidney
2 failure,fatty liver,
hyperlacticacidimi
a and severe
hypoglycemia
Type II: Pompe's Lysosomal a-1,4- Skeletal and Muscular
3 glucosidase, cardiac muscle dystrophy, severe
lysosomal acid cardiomegaly,
a-glucosidase early death.
acid maltase
Type V: McArdle's Muscle Skeletal muscle Muscle excersize-
4 phosphorylase induced cramps
and pain,
myoglobinuria
Pentose phosphate pathway
Is primarily an anabolic pathway that utilizes the 6 carbons of glucose to generate 5 carbon sugars and reducing equivalents.

The primary functions of this pathway are:

To generate reducing equivalents, in the form

1 of NADPH, for reductive biosynthesis reactions
within cells.

2 To provide the cell with ribose-5-phosphate(R5P)

for the synthesis of the nucleotides and nucleic
acids.

It can also operate to metabolize dietary pentose sugars

3 derived from the digestion of nucleic acids as well as to
rearrange the carbon skeletons of dietary carbohydrates into
glycolytic/gluconeogenic intermediates.
The Cori - cycle
The cori cycle refers to the metabolic pathway in which lactate produced by anaerobic
glycolysis in the muscles move via the blood stream to the liver where it is converted into
blood glucose and glycogen.

It is a cycle in which … glycogen in the

muscle is degraded to produce lactic acid →
1
blood→ liver → where it is changed back into
glycogen.

When needed the glycogen is broken down into

2 glucose and the blood carries the glucose to the
muscle.

3 During the muscle activity require moderate

amount of glucose, which can be supplied by the
blood glucose or breakdown of glycogen
reservoir present in the muscle tissue.
Cont.

In an actively contracting muscle, only about 8% of the

pyruvate is utilized by the citric acid cycle and the remaining is,
therefore, reduced to lactate. The lactic acid thus generated
should not be allowed to accumulate in the muscle tissues. The
muscle cramps, often associated with strenuous muscular
exercise are thought to be due to lactate accumulation. This
lactate diffuses into the blood. During exercise, blood lactate
level increases considerably. Lactate then reaches liver where it
is oxidized to pyruvate. It is then taken up through
gluconeogenesis pathway and becomes glucose, which can
enter into blood and then taken to muscle. This cycle is called
cori's cycle, by which the lactate is efficiently reutilized by the
body.
Next Lecture

Quiz

Metabolic Pathways
and
Biological Oxidation