2. CONTENTS
• Introduction
- Nutrition
- Carbohydrates
- Classification of carbohydrates
- Functions of carbohydrates
- What is metabolism?
• Major metabolic pathways of carbohydrates
- Introduction about each pathway
- Step of reactions in every metabolic pathway
- Clinical Aspects 2
3. • Polysaccharides and clinical aspects
• Role of hormones in carbohydrate metabolism
• Dental aspects of carbohydrate metabolism
• Recent issue related to carbohydrate metabolism
• Summary of carbohydrate metabolism
• Conclusion
• References
3
5. NUTRITION
• Nutrition is defined as “ the science of how the
body utilizes food to meet requirements for
development growth, repair and maintenance.”
CARBOHYDRATES
FATS
PROTEINS
VITAMINS
MINERALS
WATER
5
7. CARBOHYDRATE:
Most abundant organic molecule on earth.
Carbohydrates are defined as aldehyde or keto derivatives
of polyhydric alcohols.
For example: Glycerol on oxidation is converted to
D-glyceraldehyde, which is a carbohydrate derived from the
trihydric alcohol (glycerol).
All carbohydrates have the general formula CnH2nOn [or it
can be re-written as Cn(H2O)n ] .
7
9. FUNCTIONS OF CARBOHYDRATES
Main source of energy in the body. Energy
production from carbohydrates will be 4 k
calories/g (16 k Joules/g).
Storage form of energy (starch and glycogen).
Excess carbohydrate is converted to fat.
Glycoproteins and glycolipids are components of
cell membranes and receptors.
Structural basis of many organisms. For example,
cellulose of plants,exoskeleton of insects etc.
9
10. Biomedical Importance Of Glucose
• Glucose is a major carbohydrate
• It is a major fuel of tissues
• It is converted into other carbohydrates
Glycogen for storage.
Ribose in nucleic acids.
Galactose in lactose of milk.
They form glycoproteins & proteoglycans
They are present in some lipoproteins (LDL) .
Present in plasma membrane:glycocalyx.
Glycophorin is a major intergral membrane glycoprotein
of human erythrocytes.
10
11. Metabolism
Thousands of chemical reactions are
taking place inside a cell in an
organized, well co-ordinated and
purposeful manner; all these
reactions are called as
METABOLISM.
TYPES OF METABOLIC
PATHWAY:
Catabolic Pathway
Anabolic Pathway
Amphibolic Pathway
STAGES AND PHASES
OF METABOLISM:
Primary
Secondary
Tertiary 11
15. Entry of Glucose into cells
1) Insulin-independent transport system of glucose:
Not dependent on hormone insulin. This is operative
in – hepatocytes, erythrocytes (GLUT-1) and brain.
2) Insulin-dependent transport system: Muscles and
adipose tissue (GLUT-4).
Type 2 diabetes
melitus:
- Due to reduction
in the quantity of
GLUT-4 in
insulin
deficiency.
- Insuin resistance
is observed in
tissues. 15
17. Salient features:
1) Takes place in all cells of the body.
2) Enzymes present in “cytosomal fraction” of the cell.
3) Lactate – end product – anaerobic condition.
4) Pyruvate(finally oxidized to CO2 & H2O) – end
product of aerobic condition.
5) Tissues lacking mitochondria – major pathway – ATP
synthesis.
6) Very essential for brain – dependent on glucose for
energy.
7) Central metabolic pathway
8) Reversal of glycolysis – results in gluconeogenesis.
17
18. Reactions of Glycolysis
1) Energy Investment phase (or)
priming phase
2) Splitting phase
3) Energy generation phase
18
22. Energy production of glycolysis:
Net energy ATP utilized ATP produced
2 ATP 2ATP
From glucose to glucose -
6-p.
From fructose -6-p to
fructose 1,6 p.
4 ATP
(Substrate level
phosphorylation)
2ATP from 1,3 DPG.
2ATP from phosphoenol
pyruvate
In absence of oxygen
(anaerobic glycolysis)
8 ATP /
6 ATP (Pyruvate
dehydrogenase
2NADH,ETC,
Oxidative
phosphorylation)
2ATP
-From glucose to glucose
-6-p.
From fructose -6-p to
fructose 1,6 p.
4 ATP
(substrate level
phosphorylation)
2ATP from 1,3 BPG.
2ATP from phosphoenol
pyruvate.
+ 4ATP or 6ATP
(from oxidation of 2
NADH + H in
mitochondria).
In presence of oxygen
(aerobic glycolysis)
ATP production = ATP produced - ATP utilized
22
23. CLINICAL ASPECT
1) Lactic acidosis
- Normal value – 4 to 15 mg/dl.
- Mild forms – strenous exercise, shock,
respiratory diseases, cancers
- Severe forms – Impairment/collapse of
circulatory system – myocardial infarction,
pulmonary embolism, uncontrolled
hemmorrhage and severe shock.
23
24. 2) Cancer and glycolysis :
- Cancer cells – increased uptake of glucose and
glycolysis.
- Blood vessels unable to supply adequate oxygen –
HYPOXIC condition – Anaerobic glycolysis /
hypoxic glycolysis – Involvement of Hypoxic
inducible transcription factor (HIF).
- Treatment : Use drugs that inhibit vascularization of
tumours 24
25. Pasteur effect : Inhibition of glycolysis by
oxygen (Phosphofructokinase) .
Crabtree effect : The phenomenon of
inhibition of oxygen consumption by the
addition of glucose to tissues having high
aerobic glycolysis.
25
26. RAPARPORT – LEUBERING CYCLE
• Supplementary pathway/ Shunt pathway to glycolysis .
• Erythrocytes
• Synthesis of 2,3-bisphosphoglycerate (2,3-BPG).
• Without the synthesis of ATP.
• Help to dissipate or waste the energy not needed by RBCs.
• Supply more oxygen to the tissues.
26
27. CITRIC ACID CYCLE
KREBS CYCLE /
TRICARBOXYLIC ACID/ TCA
CYCLE
Essentially involves the oxidation of acetyl CoA
to CO2 and H2O.
This Cycle utilizes about two-third of total
oxygen consumed by the body.
27
28. Brief History:
• Hans Adolf
Krebs
• 1937
• Studies of
oxygen
consumptiom
in pigeon
breast muscle.
Location of
TCA
• Mitochondrial
matrix
• In close
proximity to
the electronic
transport
chain.
Overview
• 65-70% of the
ATP is
synthesized
• Name : TCA
used because
at the ouset of
the cycle
tricarboxylic
acids
participate.
28
29. Reactions of citric acid cycle
1) Formation of citrate : Condensation of acetyl CoA and
oxaloacetate catalysed by citrate synthase.
2) & 3) Citrate is isomerized to isocitrate aconitase (two
steps).
4) & 5) Formation of -ketoglutarate
ᾀ : enzyme isocitrate
dehydrogenase.
6) Conversion of -ketoglutarate to succinyl CoA
ᾀ :
through oxidative decarboxylation, catalysed by -
ᾀ
ketoglutarate dehydrogenase complex.
29
30. 7)Formation of succinate : enzyme succinate thiokinase
GTP + ADP ATP + GDP (nucleoside
diphosphate kinase)
8)Conversion of succinate to fumarase : enzyme
succinate dehydrogenase
9)Formation of malate : enzyme fumarase
10)Conversion of malate to oxaloacetate : enzyme
malate dehydrogenase.
30
32. • TCA cycle is strictly aerobic in contrast to glycolysis.
• Total of 12 ATP are produced from one acetyl CoA :-
During the process of oxidation of acetyl CoA via citric
acid cycle 3 NADH & 1 FADH2.
Oxidation of 3 NADH by electron transport chain
coupled with oxidative phosphorylation results in 9 ATP,
FADH2 2 ATP.
One substrate level phosphorylation.
32
34. GLUCONEOGENESIS
The synthesis of glucose from non-carbohydrate
compounds is known as gluconeogenesis.
Major substrate/precursors : lactate, pyruvate, glycogenic
amino acids, propionate & glycerol.
-Takes place in liver (1kg glucose) ; kidney matrix( 1/3rd
).
- Occurs in cytosol and some produced in mitochondria.
34
35. Importance of Gluconeogenesis
Brain,CNS,
erythrocytes,testes
and kidney medulla
dependent on
glucose for cont.
supply of energy.
Under anaerobic
condition, glucose
is the only source
to supply skeletal
muscles.
Occurs to meet the
basal req of the
body for glucose
in fasting for even
more than a day.
Effectively
clears,certain
metabolites
produced in the
tissues that
accumulates in
blood
35
37. Cori Cycle
The cycle
involveing the
synthesis of
glucose in liver
from the skeletal
muscle lactate and
the reuse of
glucose thus
synthesized by the
muscle for energy
purpose is known
as Cori cycle.
37
39. Clinical Aspects
* Glucagon stimulates gluconeogenesis:
1)Active pyruvate kinase converted to inactive form
2)Reduces the concentration of fructose 2,6-bisphosphate.
* Glycogenic amino acids have stimulating influence on gluconeogenesis.
* Diabetes mellitus where amino acids are mobilized from muscle protein for the
purpose of gluconeogenesis.
Acetyl CoA promotes gluconeogenesis:
* During starvation – due to excessive lipolysis in adipose tissue –acetyl CoA
accumulates in the liver.
* Acetyl CoA allosterically activates pyruvate carboxylase resulting in enhanced
glucose production
* Alcohol inhibits gluconeogenesis
39
40. GLYCOGEN
METABOLISM
Glycogen is a storage form of glucose in animals.
Stored mostly in liver (6-8%) and muscle (1-2%)
Due to muscle mass the quantity of glycogen in muscle = 250g
and liver =75g
Stored as granules in the cytosol.
Functions : Liver glycogen – maintain the blood glucose level
Muscle glycogen – serves as fuel reserve
40
41. GLYCOGENESIS
Synthesis of glycogen from glucose.
Takes place in cytosol.
Requires UTP and ATP besides glucose.
Steps in synthesis :
1) Synthesis of UDP- glucose
2) Requirement of primer to initiate glycogenesis
3) Glycogen synthesis by glycogen synthase
4) Formation of branches in glycogen
41
45. TYPE ENZYME DEFECT CLINICAL FEATURES
Type I (Von Gierke’s
disease)
Glucose-6-
phosphatase
deficiency.
Hypoglycemia, enlarged liver and kidneys,
gastro-intestinal symptoms, Nose bleed, short
stature, gout
Type II (Pompe’s
disease)
Acid maltase
deficiency
Diminished muscle tone, heart failure, enlarged
tongue
Type III (Cori’s
disease,Forbe disease)
Debranching enzyme
deficiency
Hypoglycemia, enlarged liver, cirrhosis, muscle
weakness, cardiac involvement
Type IV (Andersen’s
disease)
Branching enzyme
deficiency
Enlarged liver & spleen, cirrhosis, diminished
muscle tone, possible nervous system
involvement
Type V (Mcardle’s
disease)
Muscle phosphorylase
deficiency
Muscle weakness, fatigue and muscle cramps
Glycogen storage diseases
45
46. TYPE ENZYME DEFECT CLINICAL FEATURES
Type VI (Her’s
disease)
Liver phosphorylase
deficiency
Mild hypoglycemia, enlarged liver, short
stature in childhood
Type VII (Tarui’s
disease)
Phosphofructokinase
deficiency
Muscle pain, weakness and decreased
endurance
Type VIII Liver phosphorylase
kinase
Mild hypoglycemia, enlarged liver, short
stature in childhood, possible muscle weakness
and cramps
Type 0 Liver glycogen
synthetase
Hypoglycemia, possible liver enlargement
46
50. * This is an alternative pathway to glycolysis and TCA cycle
for the oxidation of glucose.
* Anabolic in nature, since it is concerned with the
biosynthesis of NADPH and pentoses.
* Unique multifunctional pathway
* Enzymes located – cytosol
* Tissues active – liver, adipose tissue, adrenal gland,
erythrocytes, testes and lactating mammary gland. 50
52. • Pentose or its derivatives are useful for the synthesis
of nucleic acids and nucleotides.
• NADPH is required :
- For reductive biosynthesis of fatty acids and steroids.
- For the synthesis of certain amino acids.
- Anti-oxidant reaction
- Hydroxylation reaction– detoxification of drugs.
- Phagocytosis
- Preserve the integrity of RBC membrane.
Significance of HMP Shunt
52
56. Alternative oxidative pathway for glucose.
synthesis of glucorinc acid,pentoses and vitamin
(ascorbic acid).
Normal carbohydrate metabolism ,phosphate esters are
involved – but in uronic acid pathway free sugars and
sugar acids are involved.
Steps of reactions :
1) Formation of UDP-glucoronate
2) Conversion of UDP- glucoronate to L-gulonate
3) Synthesis of ascorbic acid in some animals
4) Oxidation of L-gulonate
56
58. Clinical Aspects
• Effects of drugs : increases the pathway to achieve more
synthesis of glucaronate from glucose .
- barbital,chloro-butanol etc.
• Essential pentosuria : deficiency of xylitol-
dehydrogenase
- Rare genetic disorder
- Asymptomatic
- Excrete large amount of L-xylulose in urine
- No ill-effects
58
60. Disaccharide lactose present in milk – principle source of of galactose.
Lactase of intestinal mucosal cells hydrolyses lactose to galactose and
glucose.
Within cell galactose is produced by lysosomal degradation of glycoproteins
and glycolipids.
CLINICAL ASPECTS :
- Classical galactosemia : deficiency of galactose-1-phosphate
uridyltransferase. Increase in galactose level.
- Galactokinase deficiency : Responsible for galactosemia and galactosuria.
- Clinical symptoms : loss of weight in infants, hepatosplenomegaly, jaundice,
mental retardation , cataract etc.
- Treatment : removal of galactose and lactose from diet.
60
61. METABOLISM OF
FRUCTOSE
Sorbitol/Polyol Pathway:
Conversion of glucose to fructose via sorbitol.
Glucose to Sorbitol reduction by enzyme aldolase (NADPH).
Sorbitol is then oxidized to fructose by sorbitol dehydrogenase and
NAD+
.
Fructose is preferred carbohydrate for energy needs of sperm cells
due to the presence of sorbitol pathway.
Pathway is absent in liver.
Directly related to glucose : higher in uncontrolled diabetes.
61
62. METABOLISM OF
AMINO SUGARS
When the hydroxyl group of the sugar is replaced by the amino
group, the resultant compound is an amino sugar.
Eg. Glucosamine,galactosamine,mannosamine,sialic acid etc.
Essential components of glycoproteins, glycosaminoglycans,
glycolipids.
Found in some antibiotics.
20% of glucose utilized for the synthesis of amino sugars –
connective tissues.
62
63. Electron transport chain reactions
• Electron transport chain is a series of protein
complexes located in the inner membrane of
mitochondria .
63
66. • Structural components of extracellular matrix.
• Act as sieves in extracellular matrix.
• Facilitate cell migration.
• Corneal transparency.
• Anticoagulant (Heparin).
• Components of synaptic & other vesicles.
Functions of glycoaminoglycans
66
67. MPS Defect Symptoms
MPS I (Hurler
syndrome)
Alpha-L-Iduronidase Mental retardation, micrognathia, coarse facial
features, macroglossia, retinal degeneration,
corneal clouding, cardiomyopathy,
hepatosplenomegaly
MPS II (Hunter
syndrome)
Iduronate sulfatase Mental retardation (similar, but milder,
symptoms to MPS I). This type exceptionally
has X-linked recessive inheritance
MPS IIIA
(Sanfilippo A)
Heparan sulfate N
sulfatase
Developmental delay, severe hyperactivity,
spasticity, motor dysfunction, death by the
second decade
MPS IIIB
(Sanfilippo B)
Alpha-
Acetylglucosaminidase
MPS IIIC
(Sanfilippo C)
Acetyl transferase
Mucopolysaccharidoses
67
68. MPS Defect Symptoms
MPS IVA
(Morquio A)
Galactose-6-sulfatase Severe skeletal dysplasia, short stature, motor
dysfunction
MPS IVB (Morquio
B)
Beta galactosidase
MPS VI
(Maroteaux Lamy
syndrome)
N acetylgalactosamine 4
sulfatase
Severe skeletal dysplasia, short stature, motor
dysfunction, kyphosis, heart defects
MPS VII (Sly) Beta glucoronidase Hepatomegaly, skeletal dysplasia, short
stature, corneal clouding, developmental delay
MPS IX (Natowicz
syndrome)
Hyaluronidase deficiency Nodular soft-tissue masses around joints,
episodes of painful swelling of the masses,
short-term pain, mild facial changes, short
stature, normal joint movement, normal
intelligence
68
69. Hunter’s syndrome
• Short and broad mandible
• Localized radiolucent
lesions of the jaw
• Flattened
temporomandibular joints
• Macroglossia
• Conical peg-shaped teeth
with generalized wide
spacing
• Highly arched palated with
flattened alveolar ridges
• Hyperplastic gingiva
69
71. • Postabsorptive state: Blood glucose is 4.5-
5.5mmol/L.
• After carbohydrate meal: 6.5-7.2mmol/L
• During fasting : 3.3-3.9mmol/L
Regulation of Blood glucose
71
72. Metabolic & hormonal mechanisms
regulate blood glucose level
Maintenance of stable levels of glucose in blood is by
Liver.
Extrahepatic tissues.
Hormones .
72
75. Role of thyroid hormone
It stimulates glycogenolysis & gluconeogenesis.
Hypothyroid
Fasting blood glucose is
lowered.
Patients have decreased
ability to utilise glucose.
Patients are less
sensitive to insulin than
normal or hyperthyroid
patients.
Hyperthyroid
Fasting blood
glucose is elevated
Patients utilise
glucose at normal or
increased rate
75
77. Epinephrine
Secreted by adrenal medulla.
It stimulates glycogenolysis in liver & muscle.
It diminishes the release of insulin from pancreas.
77
78. Other Hormones
Anterior pituitary hormones
Growth hormone:
Elevates blood glucose level & antagonizes action of insulin.
Growth hormone is stimulated by hypoglycemia (decreases
glucose uptake in tissues)
Chronic administration of growth hormone leads to diabetes
due to B cell exhaustion.
78
84. Role of carbohydrates in dental caries
• Fermentable carbohydrates causes loss of
caries resistance.
• Caries process is an interplay between oral
bacteria, local carbohydrates & tooth surface
Bacteria + Sugars+ Teeth Organic acids
Caries
84
85. Role of carbohydrates in periodontal
disease
Abnormal
glucose metabolism
Diabetes Mellitus
Periodontal disease
Excessive carbohydrate intake
Obesity
Periodontal disease
85
87. Cystic Fibrosis
• CMD in Cystic Fibrosis is characterized by its high
rates and latent course.
• The patients with CMD have retarded physical
development, more pronounced morphofunctional
disorders in the bronchopulmonary system, lower lung
functional parameters, and more aggressive sputum
microbial composition. (Samoĭlenko VA et al.)
87
88. CMD in Gout
• OGTT causes a 34% increase in the detection rate of
T2D in patients with gout.
• Carbohydrate metabolic disturbances are revealed in
the majority of patients with gout and associated with
obesity, hypertriglyceridemia, high serum UA levels,
chronic disease forms, the high incidence of CHD and
arterial hypertension.(Eliseev MS et al.) 88
90. PER DAY INTAKE OF CARBOHYDRATE
• Carbohydrate Calculator
http://www.calculator.net/carbohydrate-calcul
ator.html?ctype=metric&cage=25&csex=f&ch
eightfeet=5&cheightinch=10&cpound=160&c
heightmeter=163&ckg=74&cactivity=1.375&
x=85&y=10#
90
91. CONCLUSION
• Carbohydrate are the measure source of energy
for the living cells. Glucose is the central
molecule in carbohydrate metabolism, actively
participating in a number of metabolic
pathway.
• One component of etiology of dental caries is
carbohydrate which act as substrate for
bacteria. Every effort should be made to
reduce sugar intake for healthy tooth.
91
92. REFERENCES
1) Biochemistry – U.Satyanarayana-3rd
Ed.
2) Textbook of Biochemistry- D.M.Vasudevan -
14th
Ed.
3) Textbook of Medical Biochemistry –
M.N.Chattergy – 17th
Ed.
4) Text book of Physiology –Ganong – 24th
Ed.
5) Text book of Oral Pathology – Shafers- 7th
Ed.
6) Principles & practice of Medicine-Davidson –
21st
Ed.
92
![CARBOHYDRATE:
Most abundant organic molecule on earth.
Carbohydrates are defined as aldehyde or keto derivatives
of polyhydric alcohols.
For example: Glycerol on oxidation is converted to
D-glyceraldehyde, which is a carbohydrate derived from the
trihydric alcohol (glycerol).
All carbohydrates have the general formula CnH2nOn [or it
can be re-written as Cn(H2O)n ] .
7](https://image.slidesharecdn.com/macronutrientscho-250310113554-2645f6af/85/Macronutrients-CHO-pptx-to-be-download-7-320.jpg)
![Energy
Investment
Phase
•
Glucose
is
phosphorylated
to
glucose-6-phosphate
by
hexokinase
(or)
glucokinase.
•
Glucose-6-phosphate
undergoes
isomerization
to
give
fructose
-6-
phosphate
in
the
presense
of
phospho-hexose
isomerase
and
Mg
2+
•
Fructose-6-phosphate
is
phoshorylated
to
fructose
1,6-bisphosphate
by
phosphofructokinase.
Splitting
Phase
•
Fructose
1,6-bisphosphate
glyceraldehyde
3-phosphate
+
dihydroxyacetone
phosphate.(aldolase
enzyme)
•
2
molecules
of
glyceraldehyde
3-phosphate
are
obtained
from
1
molecule
of
glucose
Energy
Generation
Phase
•
Glyceraldehyde
3-phosphate
1,3-bisphosphoglycerate(glyceraldehyde
3-phosphate
hydrogenase
)
•
1,3-bisphosphoglycerate
3-phosphoglycerate
(phosphoglycerate
kinase)
•
3-phosphoglycerate
2-phosphoglycerate
(phosphoglycerate
mutase)
•
2-phosphoglycerate
phosphoenol
pyruvate
(enolase
+
Mg
2+
&
Mn
2+
)
•
Phosphoenol
pyruvate
pyruvate
[enol]
(pyruvate
kinase
)
pyruvate
[keto]
L-Lactate
(lactate
dehydrogenase)
19](https://image.slidesharecdn.com/macronutrientscho-250310113554-2645f6af/85/Macronutrients-CHO-pptx-to-be-download-19-320.jpg)
![• Glucose-6-Phosphate dehydrogenase
deficiency :
- Inherited sex-linked trait
- Red blood cells
- Impaired synthesis of NADPH
- hemolysis , developing hemolytic anemia
Resistance towards malaria [Africans]
Clinical Aspects
53](https://image.slidesharecdn.com/macronutrientscho-250310113554-2645f6af/85/Macronutrients-CHO-pptx-to-be-download-53-320.jpg)
