Carbo metabolism

Definition:
Glycolysis is defined as the sequence of reactions for the breakdown of Glucose (6-carbon
molecule) to two molecules of pyruvic acid (3-carbon molecule) under aerobic conditions; or
lactate under anaerobic conditions along with the production energy in the form of ATP
(Adenosine Triphosphate).
This pathway was described by Embden, Meyerhof and Parnas. Hence, it is also called as
Embden-Meyerhof pathway (EM pathway). In The Glycolytic pathway oxidation of
glucose to pyruvate takes place with the generation of ATP and NADH.
Net Reaction: Glucose + 2NAD+ + 2Pi + 2ADP = 2Pyruvate + 2ATP + 2NADH + 2H2O
Site of Glycolysis
Glycolysis occurs in the Cytosol or Cytoplasm of all the cells of the body.
Two types of Glycolysis
Phases of Glycolysis:
Glucose is converted to Pyruvate in 10 steps by glycolysis. The glycolytic patway can be
divided into two phases:
1. Preparatory Phase
This phase is also called glucose activation phase. In this phase two molecules of ATP are
consumed and the hexose chain is cleaved into two triose phosphates. During this,
phosphorylation of glucose and it’s conversion to glyceraldehyde-3-phosphate take place.
The steps 1, 2, 3, 4 and 5 together are called as the preparatory phase.
2. Payoff Phase
This phase is also called energy extraction phase. During this phase, conversion of
glyceraldehyde-3-phophate to pyruvate and the coupled formation of ATP take place. The
steps after 5 constitute payoff phase.
Aerobic Glycolysis: Anaerobic Glycolysis:
It occurs when oxygen is plentiful It occurs when oxygen is scarce
Final product is pyruvate along with the
production of eight ATP molecules
Final product is lactate along with the
production of two ATP molecules
Under aerobic conditions, pyruvate
converted by pyruvate dehydrogenase to
acetyl coenzyme A (CoA) which can then
enter the citric acid cycle.
Under anaerobic conditions, pyruvate is
converted to lactate by lactate dehydrogenase
(LDH). When oxygen becomes available, the
lactate is converted back to Pyruvate.
GLYCOLYSIS
Gaurav Saxena GNIT College of Pharmacy

Reactions of Glycolysis (Trick PIPLIOSIDS)
1. Phosphorylation: Uptake and phosphorylation of Glucose to Glucose-6-Phosphate
with the consumption one ATP.
2. Isomerization: Isomerization of Glucose-6-Phosphateto to Fructose-6-Phosphate.
3. Phosphorylation: Phosphorylation of Fructose-6-Phosphate to Fructose-1,6-
Biphosphate with the consumption one ATP.
4. Lysis: Cleavage of Fructose-1, 6-Biphosphate to two molecule Glyceraldehyde 3
phosphate.
5. Isomerization: Isomerization of Glyceraldehyde 3 phosphate (GAP) to DHAP
(Dihydroxyacetone Phophate).
6. Oxidation by dehydrogenation: Oxidative phosphorylation of GAP to 1,3-
Bisphosphoglycerate with the formation of two molecule NADH (Necotinamide
adenine dinucleotide)
7. Substrate level phosphorylation: Conversion of 1, 3-Bisphosphoglycerate to 3-
Phosphoglycerate with the formation of ATP.
8. Isomerization: Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate
9. Dehydration: Conversion of 2-Phosphoglycerate to Phosphoenolpyruvate with the
release of water molecule.
10. Substrate level phosphorylation: Conversion of Phosphoenol Pyruvate to Pyruvate
with the formation of ATP.
Energetics of Glycolysis
A. Aerobic Glycolysis
B. Anaerobic Glycolysis
Step Enzyme Source No. of ATP
1 Hexokinase – -1
3 Phosphofructokinase – -1
6 Glyceraldehyde-3- phosphate dehydrogenase NADH (3) x 2 = 6
7 Phosphoglycerate kinase ATP (1) x 2 = 2
10 Pyruvate kinase ATP (1) x 2 = 2
Net Yield 8 ATPs
Step Enzyme Source No. of ATP
Formed/consumed
1 Hexokinase – -1
3 Phosphofructokinase – -1
7 Phosphoglycerate kinase ATP (1) x 2 = 2
10 Pyruvate kinase ATP (1) x 2 = 2
Net Yield 2 ATPs

Significance of the Glycolytic Pathway
1. Glycolysis is a universal pathway, taking place in all organisms, from yeast to
mammals.
2. Glycolysis can be function either aerobically or anaerobically. In the presence of O2,
pyruvate is further oxidized to CO2. In the absence of O2, pyruvate can be fermented
to lactate or Ethanol.
3. Glycolysis is the only source of energy in erythrocytes due to lack of mitochondria.
4. Main way to produce ATP in some tissue (RBC, retina, testis, skin, medulla of kidney)
5. During strenuous exercise, when muscle tissue lacks enough oxygen, anaerobic
glycolysis forms the major source of energy for muscles.
6. The glycolytic pathway may be considered as the preliminary step before complete
oxidation.
7. The glycolytic pathway provides carbon skeletons for synthesis of non-essential
amino acids.
8. DHAP and Glyceraldehyde 3 phosphate, important for Lipogenesis (glycerol part of
fat.)
9. Most of the reactions of the glycolytic pathway are reversible, which are also used for
gluconeogenesis.

NAD+
NADH + H+
Mg2+
Mg2+
1
2
8
9
7
3
4
10
6
PREPARATORY PHASE
Phosphorylation of Glucose and its
conversion to Glyceraldehydes-3-
Phosphate
5
Phosphoglycerate Kinase
STEPS
GLYCOLYSIS
Anaerobic glycolysis
3 ADP +Pi 3 ATP
½ O2
H2O
Aerobic glycolysis
Mitochondrial respiratory chain
Glucose 6-phospate (6C)
Glyceraldehyde 3-phosphate (3C) Dihydroxyacetone-phosphate (3C)
GLUCOSE (6C)
ATP
ADP
Glucose 6-phospate isomerase
Phospho-fructokinase-I
Aldolase
Triosephosphate isomerase
Fructose 6-phospate
ATP
(2) Glyceraldehyde 3-phosphate (3C)
(2) 3-Phosphoglycerate (3C)
(2) 2-Phosphoglycerate (3C)
(2) Pyruvate (3C) Lactate
2NAD+
2NADH +H+
(2)1, 3 Biphosphoglycerate (3C)
2ADP
2ATP
Mg2+
(2) Phosphoenolpyruvate (3C)
2ADP
2ATP
Mg2+
Glyceraldehyde 3-Phosphate
dehydrogenase
Phosphoglycerate Mutase
Enolase
Pyruvate Kinase
Lactate dehydrogenase
2H2O
Hexokinase
First priming reaction
Second priming reaction
ADP
Fructose 1, 6-diphospate (6C)
Cleavage of 6- Carbon sugar phosphate to two 3-carbon Sugar
phosphate
PAY OFF PHASE
Oxidative conversion of Glyceraldehydes-3-
Phosphate to Pyruvate & the coupled
formation of ATP and NADH
REACTIONS OF GLYCOLYSIS
Trick-- PIPLIOSIDS
1.Phosphorylation
2.Isomerization
3.Phosphorylation
4.Lysis
5.Isomerisation
6.Oxidation
7.Substrate Level Phosphorylation
8.Isomerisation
9.Dehydration
10. Substrate Level
Phosphorylation

Definition
The citric acid cycle also known as the Tricarboxylic acid cycle (TCA) cycle or the
Krebs cycle is a series of chemical reactions for the oxidation of Acetyl CoA derived
from carbohydrates, fats and proteins into carbon dioxide, water and chemical energy in
the form of Adenosine Triphosphate (ATP).
Location
The citric acid cycle occurs in the matrix of the mitochondria in eukaryotic cells. It is the
second stage of cellular respiration.
Figure 1: Cellular Respiration
Description
1.This cycle was discovered by British biochemist Hans Krebs hence it is also known as
Krebs cycle also
2. It is also known as Citric acid cycle or Tricarboxylic acid cycle because the first product
of Krebs cycle is Citric acid (Citrate). It is called as tricarboxylic acid cycle because the
citric acid contains three carboxyl groups.
3. After glycolysis, Pyruvate enters mitochondria. Here it undergoes a link reaction, losing
a carbon atom (as carbon dioxide) and hydrogen (as reduced NAD). The resulting compound
is Acetyle CoA. The actual Krebs cycle begins when acetyl –CoA enters into a reaction to
form citric Acid. Its substrate Acetyl Co-A is connecting link between glycolysis and Krebs
cycle. The oxalacetate acts as acceptor molecule. Although the citric acid cycle does not use
oxygen directly, it works only when oxygen is present.
ATP ATP ATP
Electron carried
by NADH and
FADH2
Substrate level phosphorylation Substrate level phosphorylation Oxidative phosphorylation
Cytosol
Mitochondria
Electron carried
by NADH
Glycolysis
Glucose Pyruvate
Oxidative
phosphorylation:
Electron transport chain
and chemiosmosis
Citric acid
cycle

Reaction of Citric Acid Cycle
Dehydration
Hydration
SubstrateLevel
Phophorylation
Dehydrogenation
2
3
4
5
Decarboxylation
6
Oxidative Decarboxylation
7
8
9
Hydration
Dehydrogenation
10
SUCCINATE
FUMARATE
OXALO-ACETATE
PYRUVATE
ACETYLCoA
Pyruvate
dehydrogenase
complex
Citrate synthetase
Aconitase
Aconitase
Isocitrate
Dehydrogenas
Oxalosuccinate
Decarboxylase
α-ketogluterate
dehydrogenase
complex
Succinyl thiokinase
Malate Dehydrogenase
Fumarase
Fatty acid,
Ketone
Dehydrogenation
NAD+
Glucose,
Amino acid
NAD+
CO2
NADH + H+
CoASH
2
H O
CIS-ACONITATE
H2O
NADH + H+
CO2
CO2 NADH + H+
GTP
GDP
FAD
FADH2
H2O
NAD
NADH +H+
CoA
CITRATE
(6C)
ISO-CITRATE
(6C)
OXALO-SUCCINATE
(6C)
α-KETOGLUTARATE
(5C)
NAD+
SUCCINYL CoA
(4C)
(4C)
(4C)
Succinate
Dehydrogenase
MALATE
(4C)
(4C)
(2C)
(3C)
H2O
1
Condensation

Energetic of TCA cycle
Step number Reaction Co-enzyme ATP
4 & 5 Isocitrate Oxalosuccinate NADH 3
6 α- Keto gluterate Succinyl CoA NADH 3
7 Succinyl CoA Succinate GTP (ATP) 1
8 Succinate Fumarate FADH2 2
10 Malate Oxalo acetate NADH 3
Total 12
Significance of Citric acid cycle
1. Central metabolic/Common oxidative pathway: Citric acid cycle is the common
metabolic pathway for oxidation of Carbohydrate, Lipid, and protein because
glucose, fatty acid and many amino acids are metabolized to acetyl CoA which is
finally oxidized in the citric acid cycle.
2. Complete oxidation of Acetyl CoA to CO2 and H2O and release of energy.
3. ATP generation: The reducing equivalent in the form of hydrogen or electron in the
cycle enters the respiratory chain, where large amount high energy phosphates (ATP)
are generated by oxidative Phosphorylation.
4. The cycle provides precursors of certain amino acids, as well as the reducing agent
NADH that are used in numerous other biochemical reactions.
5. The citric acid cycle in amphibolic (dual) in nature (both catabolic and anabolic).
Involved in the glucose, fatty acid and amino acid synthesis.

Trick to remember TCA cycle
Total 10 steps and 10 molecules in cycle
Steps 1, 5, 6, 7 is irreversible steps
Oh Citric Acid Is Of (Course) A Silly Stupid Funny Molecule
I. A. M - NADH
Silly - GTP
Stupid - FADH2
H2O
H2O
1. Oh
2. Citric
3. Acid
4. Is
5. Of (Course) -
- Oxaloacetate
- Citrate
- Cis- Aconitate
- Iso citrate
Oxalo- Succinate
H2O
NADH
CO2
NADH, CO2
GTP
FADH2
H2O
6. A
7. Silly
8. Stupid
9.Funny
10.Molecule
- Alpha Ketogluterate
- Succinyl CoA
- Succinate
- Fumarate
- Malate NADH

Definition: Gluconeogenesis is the synthesis of glucose from Pyruvate and other non-
carbohydrate compounds (lactate, glycogenic amino acid, propionate and glycerol).
Location: Gluconeogenesis occurs in the in the cytosol and partly in the mitochondria of the cell
of liver, kidney cortex and epithelial cells of the small intestine.
A. Reaction of Gluconeogenesis from Pyruvate
1. Conversion of Pyruvate to Phosphoenol pyruvate
a. Pyruvate Oxaloacetate
(In mitochondrial matrix)
Transport to cytosol after
converting to malate
Phosphoenol Pyruvate (PEP)
b. Oxaloacetate
(In cytosol malate
converts to oxaloacetate)
GLUCONEOGENESIS
2. Conversion of fructose 1,6 biphosphate to fructose-6-phosphate
3. Conversion of glucose-6-Phosphate to glucose
Glucose
Pyruvate carboxylase
Phosphoenol Pyruvate carboxykinase
CO2
GTP CO2
ATP ADP
GDP

Figure 2: GLUCONEOGENESIS
GLYCOLYSIS
GLUCONEOGENESIS

B. Gluconeogenesis from Glycerol
acid result in the formation of pyruvate or
C. Gluconeogenesis from Amino Acid
The carbon skeleton of glucogenic amino
inyermediates of citric acid cycle
Significance of Gluconeogenesis
1. Replenishment of glucose and maintenance of normal blood glucose levels especially
under the condition of starvation, prolong fasting and in diabetes mellitus.
2. Replenishment of liver glycogen.
3. Important role in blood sugar Homeostasis.
4. Regulation of acid base balance.
5. It clears the blood lactate produced by muscle & RBC and glycerol produced by
adipose tissue.
Liberated in adipose
tissue by hydrolysis
of fat
Used for glycolysis
or gluconeogensis

1. The Hexose Monophosphate Shunt is also known as Pentose phosphate Pathway
(PPP) or Phosphogluconate pathway.
2. This is an alternative Glucose oxidation pathway.
3. The pentose phosphate pathway takes place in the Cytosol.
4. Its primary role is anabolic rather than catabolic.
5. Biosynthesis of NADPH and Pentoses.
6. Steroidogenic tissues, red blood cells and liver are the major sites of hexose
Non-oxidative reactions
monophosphate pathway.
7. The pentose phosphate pathway divided into two phases:
A. Oxidative phase: Each molecule of Glucose-6-Phosphate oxidized to Ribulose-
5-Phosphate. It generates NADPH with the release of CO2.
B. Non-oxidative phase: Catalyzes the inter-conversion of 3, 4, 5 and 7- carbon
sugars. Synthesize pentose-phosphate and other phosphate monosaccharides.
Oxidative Stage of Pentose Phosphate Pathway
Glucose-6-phosphate
NADP+
NADPH
NADPH
CO2
Ribulose-5-phosphate
Glucose-6-phosphate
dehydrogenase
6-Phosphogluconolactone
H2O
Gluconolactonase
H+
6-Phosphogluconate
NADP+
6-Phosphogluconate
dehydrogenase
Hexose Monophosphate Shunt

Significance of HMP Shunt
1. It is a source of NADPH and ribose-5-Phosphate.
2. The NADPH is required for the biosynthesis of fatty acid an steroids, drug reduction
(detoxification of drugs and foreign compounds), synthesis of certain amino acids
involving the enzyme glutamate dehydrogenase, phagocytosis and as a cofactor for
some non-synthetic enzymatic reactions.
3. The Ribose-5- Phosphate required for nucleic acid biosynthesis (RNA and DNA).
4. NADPH involved in Antioxidant (Free radical scavenging) reaction. Gltathione
mediated reduction of H2O2.
5. High concentration of NADPH in lens of eye is necessary to preserve the
transparency of the lens.
Ribulose-5-phosphate
Xylulose-5-phosphate Ribose-5-phosphate
Sedoheptulose-7-phosphate Glyceraldehyde-3-phosphate
Erythrose-4-phosphate
Fructose-6-phosphate
Fructose-6-phosphate
Ribulose-5-phosphate isomerase
Ribulose-5-phosphate 3-epimerase
Transketolase
Transaldolase
Transketolase
Glyceraldehyde-3-phosphate
Non-Oxidative Stage of Pentose Phosphate Pathway

6. In the Hexose MonoPhosphate Shunt Pathway, few molecules of Glycolytic
intermediates (Glyceraldehyde-3-Phosphate and Fructose-6-Phosphate) are produced
these are directly involves in Glycolysis.
7. NADPH is also required to preserve the integrity of RBC membrane.
Trick to Remember Non Oxidative Pathway:
Ribulose-5-Phosphate
5C’ 5C
7C 3C
1. Glyceraldehyde-3- phosphate (3C)
2. Erythrose -4-phosphate (4C)
3. Xylulose-5- phosphate (5C’)
4. Ribose-5- phosphate (5C)
5. Fructose-6- phosphate (6C)
6. Sedoheptulose-7- phosphate (7C)
(5C’): (5C)
(7C): (3C)
(4C): (6C)
(5C’): (4C)
(3C): (6C) 4C 6C
3C 6C

Glycogen is a readily mobilized storage form of glucose.
It is a very large, branched polymer of glucose residues that can be broken down
to yield glucose molecules when energy is needed.
Most of the glucose residues in glycogen are linked by α-1,4-glycosidic bonds.
Branches at about every tenth residue are created by α-1,6-glycosidic bonds..
The highly branched structure of glycogen provides many sites for glycogenolysis,
permitting rapid release of glucose 1-phosphate for muscle activity.
GLYCOGEN- METABOLISM
Glycogen is present in the cytosol in the form of granules ranging in diameter from 10 to 40
nm.
It has a molecular mass of 107 Da and consists of polysaccharide chains, each containing
about 13 glucose residues.
The chains are either branched or unbranched and are arranged in 12 concentric layers.
The branched chains (each has two branches) are found in the inner layers and the
unbranched chains in the outer layer. (G, Glycogenin, the primer molecule for glycogen
synthesis.)
Glycogen Storage Sites
It is stored mainly in liver and muscle
The liver content of glycogen is greater than that of muscle,
Since the muscle mass of the body is considerably greater than that of the liver, about
three-quarters of total body glycogen is in muscle
Reason for Storing Glycogen as fuel
Glycogen serves as a buffer to maintain blood-glucose levels.
Glucose is virtually the only fuel used by the brain, except during prolonged
starvation.
The glucose from glycogen is readily mobilized and is therefore a good source of
energy for sudden, strenuous activity.
Unlike fatty acids, the released glucose can provide energy in the absence of oxygen
and can thus supply energy for anaerobic activity.

Glycogen metabolism is synthesis and breakdown of glycogen. It is a very large, branched polymer of
glucose residues that can be broken down to yield glucose molecules when energy is needed. The
pathway for the synthesis and degradation of glycogen is not reversible.
Definition: The synthesis of glycogen from glucose is called glycogenesis
Location: Cytosol of Liver and Muscle cell
Requirements: ATP (Adenosine triphosphate), UTP (Uridine Triphosphate), Glucose
Steps:
1. Synthesis of UDP glucose
2. Requirement of primer to initiate glycogenesis
3. Glycogen synthesis by glycogen synthase
4. Formation of branches in glycogen
Definition: The breakdown or degradation of stored glycogen into glucose is called
glycogenolysis. Glycogen is degraded by breaking α 1, 4-bonds and α 1, 6-bonds glycosidic
bond. Location: Cytosol of Liver and Muscle cell
Steps:
Glycogen degradation consists of three steps:
(1) The release of glucose 1-phosphate from glycogen,
(2) The remodeling of the glycogen substrate to permit further degradation, and
(3) The conversion of glucose 1-phosphate into glucose 6-phosphate for further metabolism.
GLYCOGEN- METABOLISM
GLYCOGENESIS
GLYCOGENOLYSIS
Muscle glycogen provides a readily available source of glucose for glycolysis within
the muscle itself.
Liver glycogen functions to store and export glucose to maintain blood glucose
between meals.

Limit dextrin
GLYCOGENOLYSIS
Breakdown of glycogen into glucose
Glucose
‘The Power of Body’
Further action of Phosphorylase
Debranching enzyme (α 1-6 glucosidase activity)
Debranching enzyme (Tranferase activity)
Glycogen
α 1, 6-bond α 1, 4-bonds
Glycogen Phosphorylase
Glucose-1-Phosphate
Phosphoglucomutas
Glucose-6-Phosphate Glycolysis
Glucose-6-Phosphatase (In Liver and Kidney only)
1. Phosphorylasis
Glycogen phosphorylase cleave α 1, 4 glycosidic bonds
sequentially (from non reducing end of glycogen) to yield
glucose 1 phosphate, continues until 4 glucose residues remain
on the either side of branching to form limit dextrin.
Pi
Free Glucose
1
2
3
4
5
6
2. Debranching
Glycosyl tranferase removes fragments of
3-4 glucose of branch chain and transfer
them to another chain
Glucose-1-Phosphate
3. Cleavage of α 1, 6-bond by α
1-6 glucosidase activity. Release
of a free glucose
4. Remaining molecule of glycogen is again
cleaved by phosphorylase and debranching
enzyme to repeat the reaction 1 to 3.
5. Isomerization
Byphosphoglumutase
6. Release of phosphate group from glucose 6
phosphate by glucose 6 phophatase in liver and
kidney to form glucose

16
α 1, 4-bonds
Mg2
16
11
Glucose
ATP
UDP
ADP
Glucose-6-phosphate
Glycogen Primer
O
O
3
1
O
1 2
Further elongation of glycogen by
glycogen synthase forming α 1, 4-
bonds
Glycogen
The Reserve Fuel of Body
Branching by glucosyl 4, 6 transferase
forming α 1, 6-bonds
α 1,6-bonds
Glucosyl 4, 6 transferase
(Branching enzyme)
7 10
Glycogen syntheses
10
UDP-Glucose
OH
Glycogen initiator synthasis
Phosphoglucomutas
Glucokinase
UDP glucose phosphorylase
UDP-
Glycogenin
13UDP-
UDP
1
GLYCOGENESIS
Storage of glucose into glycogen to serve you later (when your body really needs it)
Phosphorylation
Glucose-1-phosphate
UTP
PPi
Isomerisation
UDP- Uridine
Diphosphate Glucose Synthesis
Glyocgenin protein accept glucose
from UDPG to from glycogen primer to
initiate glycogen synthesis
Glycogen synthase
Transfer Glucose from UDPG to the
non reducing end of glycogen
formation to form α 1, 4 glycosidic
linkages
Formation of branches in
glycogen by glucosyl 4, 6
transferase

Both synthesis & breakdown of glycogen are spontaneous. If
both pathways were active simultaneously in a cell, there
would be a "futile cycle" with cleavage of one ~P bond per
cycle (in forming UDP-glucose).To prevent this both pathways
are reciprocally regulated
BIOENERGETICS OF GLYCOGENESIS AND GLYCOGENOLYSIS
One ATP is hydrolyzed incorporating glucose 6- phosphate into
glycogen.
The energy yield from the breakdown of glycogen is highly
efficient.
About 90% of the residues are phosphorolytically cleaved to
glucose 1-phosphate, which is converted at no cost into
glucose 6-phosphate.
The other 10% are branch residues, which are hydrolytically
cleaved.
One molecule of ATP is then used to phosphorylate each of
these glucose molecules to glucose 6- phosphate.
Glycogen Storage Diseases "Glycogen storage disease" is a
generic term to describe a group of inherited disorders
characterized by deposition of an abnormal type or quantity
of glycogen in tissues, or failure to mobilize glycogen.

GLYCOGEN STORAGE DISESASE
Metabolic defect in the glycogen synthesis and degradation are collectively known as Glycogen
storage disease (GSD). In these condition, deposition of normal or abnormal type of glycogen in
one or more tissue.
GLYCOGEN STORAGE DISEASES A group of diseases results from genetic defects of certain
enzymes. The absence of glucose-6-phosphatase enzyme results in the classical hepatorenal
glycogen storage disease Von Gierke (type I), this is characterized by : 1- It occurs in only 1
person per 200,000 and is transmitted as an autosomal recessive trait. 2- Symptoms include :
Fasting hypoglycemia, because the liver cannot release enough glucose by means of
glycogenolysis; only the free glucose from debranching enzyme activity is available. 3- Lactic
academia, because the liver cannot form glucose from lactate .The increased blood lactate
reduces blood pH and the alkali reserve. 4- Hyperlipidemia, because the lack of hepatic
gluconeogenesis (results in increased mobilization of fat as a metabolic fuel). 5- Hyperuricemia
(with gouty arthritis), due to hyperactivity of the hexose monophosphate shunt Other types of
glycogenoses A number of other genetic glycogen storage defects (glycogenoses) have been
described. Pompe’s (lysosmal glucosidase deficiency), Forb’s (Debranching enzyme deficiency),
Andersen’s (Branching enzyme system deficiency), Macardle’s (Muscle phosphorylase
deficiency), Here’s (Liver phosphorylase deficiency) and Taui’s (Phosphofuctokinase deficiency).
Glycogen Storage Diseases

Type
Name Enzyme
Deficien
cy
Clinical Features
0
— Glycog
en
synthas
e
Hypoglycemia;
hyperketonemia
; early death
I Von Gierke's
disease
Glucose 6-
phosphatase
Glycogen
accumulation in
liver and renal
tubule cells;
hypoglycemia;
lactic acidemia;
ketosis;
hyperlipemia
Pompe’s Disease
Lysosomal 14
and 16
Accumulation
of glycogen in
lysosomes
juvenile onset
glucosidase
s
i
s
i
II

Type Name Biochemic
al defect
Clinical Features
III Limit dextrinosis,
Forbe's or Cori's
disease
Debranching
enzyme
Fasting
hypoglycemia;
hepatomegaly
in infancy;
accumulation of
characteristic
branched
polysaccharide
IV Amylopectinosis,
Andersen's
disease
Branching
enzyme
Hepatosplenom
egaly;
accumulation of
polysaccharide
with few branch
points; death
from heart or
liver failure in
f8
i/
r
1
s
2
t
/20
y
1
e
2
ar of
life
58

Type Name Biochemical defect Clinical Features
V Myophosphorylase
deficiency,
McArdle's
syndrome
Muscle
phosphorylase
Poor exercise
tolerance; muscle
glycogen
abnormally high
(2.5–4%); blood
lactate very low
after exercise
VI Hers' disease Liver
phosphorylase
Hepatomegaly;
accumulation of
glycogen in liver;
mild
hypoglycemia;
generally good
prognosis
59

Type Name
VII Tarui's disease
se 1
Biochemical defect Clinical Features
Muscle and Poor exercise
erythrocyte tolerance; muscle
phosphofructokina glycogen
abnormally high
(2.5–4%); blood
lactate very low
after exercise; also
hemolytic anemia
VIII Liver
phosphorylase
kinase
Hepatomegaly;
accumulation of
glycogen in liver;
mild
hypoglycemia;
generally good
prognosis
8/12/2012 60

Type Name Biochemical defect Clinical Features
IX Liver and
muscle
phosphorylase
kinase
Hepatomegaly;
accumulation
of
glycogen in liver
and muscle;
mild
hypoglycemia;
generally good
prognosis
X cAMP-
dependent
protein kinase A
Hepatomegaly;
accumulation of
glycogen in
liver

GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY (G6PD)
Definition: An X-linked genetic enzyme deficiency resulting in abnormal metabolism in red
blood cell and can cause haemolysis usually after exposure to certain medications, foods, or
even infections.
G6PD deficiency is a genetic abnormality that results in an inadequate amount of glucose-6-
phosphate dehydrogenase (G6PD) in the blood. It is inherited as an X-linked recessive
disorder. Glucose-6-phosphate dehydrogenase or G6PD, helps red blood cells (RBCs)
function normally. This deficiency can cause hemolytic anemia, usually after exposure to
certain medications, foods, or even infections.
Pathophysiology
Normally red cells are protected from the action of free radicals by glutathione. NADPH
produced in erythrocytes by pentose phosphate pathway is used to keep the glutathione in
reduced state, reduced glutathione (GSH) which is essentially required to:
1. Preserve the integrity of RBC membrane.
2. Keep the ferrous ion (Fe2+
) of hemoglobin in the reduced state so that accumulation of
methemoglobin (Fe3+
) is prevented, because accumulation of methhemoglobin and
peroxides in erythrocytes leading to hemolysis.
3. G6PD also protects red blood cells from potentially harmful byproducts, certain
medications or an infection.
HMP shunt is only means of
providing NADPH in the
erythrocytes.
Deficiency of G6PD impairs the synthesis
of NADPH in RBC which maintain the
reduced form of glutathione which is
essential for RBC
G6PD deficiency causes breakdown of
red blood cells, when the body is exposed
to certain drugs or the stress of infection.
Figure 1: Pentose Phosphate pathway

Figure 2: G6PD deficiency
*
ROS: Reactive oxygen species

Causes
The defective gene that causes G6PD deficiency is on the X chromosome. Men have only one
X chromosome, while women have two X chromosomes. In males, one altered copy of the
gene is enough to cause G6PD deficiency. In females, however, a mutation would have to
occur in both copies of the gene. Since it is unlikely for females to have two altered copies of
this gene, males are affected by G6PD deficiency much more frequently than females. In
people with G6PD deficiency, hemolytic anemia can occur after eating fava beans or certain
legumes. It may also be triggered by infections or by certain drugs, such as antimalarials,
sulfonamides, a medication used for treating various infections, aspirin, some nonsteroidal
anti-inflammatory medications (NSAIDs).
Symptoms
In more serious cases, a child may exhibit symptoms of hemolytic anemia (also known as a
hemolytic crisis), including, rapid heart rate, shortness of breath, fever, fatigue, dizziness,
paleness, jaundice, or yellowing of the skin and eyes particularly in new born, paleness (in
darker-skinned kids, paleness is sometimes best seen in the mouth, especially on the lips or
tongue), dark, tea-colored urine.
Diagnosis
1. Complete blood count and reticulocyte count.
2. In active G6PD deficiency, Heinz bodies can be seen in red blood cells on a blood
film.
3. Liver enzymes (to exclude other causes of jaundice).
4. Lactate dehydrogenase (elevated in hemolysis and a marker of hemolytic severity)
Haptoglobin (decreased in hemolysis).
5. A direct antiglobulin test (Coombs' test)
6. Beutler fluorescent spot test visually identifies NADPH produced by G6PD
under ultraviolet light. When the blood spot does not fluoresce, the test is positive.
Treatment
Treatment for G6PD deficiency consists of removing the trigger that is causing symptoms. If
the condition was triggered by an infection, then the underlying infection is treated
accordingly. Medications that may be destroying red blood cells are also discontinued. Once
G6PD deficiency has progressed to hemolytic anemia, treatment usually includes oxygen
therapy and a blood transfusion to replenish oxygen and red blood cell levels.

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