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GUANGDONG OCEAN UNIVERSITY
Carbohydrates Metabolism
(糖代谢---táng dài xiè)
Presenter: Muhammad Waseem (Ghani)
Class: Advanced Biochemistry
Contents
25/03/2019 2
Overview
CARBOHYDRATES:
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
25/03/2019 3
CLASSIFICATION OF CARBOHYDRATE
25/03/2019 4
Importance and functions of Carbohydrates
Carbohydrates constitute the largest component of an average diet
The most important function of carbohydrates is to provide energy
Storage form of energy (starch and glycogen)
Energy production from carbohydrates will be 4 k calories/g (16 k
Joules/g).
Excess carbohydrate is converted to fat.
Some tissues, e.g. brain and erythrocytes, get energy almost
exclusively from glucose
If the conditions become anaerobic, only glucose can be used as a fuel
25/03/2019 5
Importance and functions of Carbohydrates
Ribose and deoxyribose are used to synthesize nucleotides and
nucleic acids
Some carbohydrates form the prosthetic group of hormones,
immunoglobulins, blood group substances etc.
Some carbohydrates act as structural constituents of tissues
Structural basis of many organisms. For example, cellulose of plants,
exoskeleton of insects etc.
Glycoproteins and glycolipids are components of cell membranes and
receptors.
25/03/2019 6
Over view of Carbohydrate Metabolism
The entire spectrum of chemical reactions, occurring in the living
system are referred as “Metabolism”
Types of metabolic pathways in cellular metabolism
1. Anabolic pathways: Protein synthesis.
2. Catabolic Pathways: Oxidative phosphorylation
3. Amphibolic pathways: Citric acid cycle.
• Cells break down excess carbohydrates first, then lipids, finally amino acids if
energy needs are not met by carbohydrates and fat
• Nutrients not used for energy are used to build up structure, are stored, or excreted
• 40% of the energy released in catabolism is captured in ATP, the rest is released as
heat
25/03/2019 7
Carbohydrate Metabolism
• Primarily glucose
Fructose and galactose enter the pathways at
various points
All cells can utilize glucose for energy
production
Glucose uptake from blood to cells usually
mediated by insulin and transporters
Liver is central site for carbohydrate
metabolism
Glucose uptake independent of insulin
The only exporter of glucose
25/03/2019 8
Digestion and Absorption of Carbohydrates
25/03/2019 9
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)
25/03/2019 10
Metabolism
There are six major
metabolic pathways
of glucose:
1) Glycogenesis
2) Glycogenolysis
3) Gluconeogenesis
4) Hexose monophosphate
shunt
5) Glycolysis
6) Citric Acid Cycle
25/03/2019 11
Glycolysis
Glycolysis is defined as the sequence of
reactions converting glucose (or glycogen) to
pyruvate or lactate, with the production of ATP
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
25/03/2019 12
• A series of reactions in
the cytoplasm which
converts glucose (C6) to
two molecules of
pyruvate (a C3
carboxylate), and ATP
and NADH are
produced.
• Also called Embden-
Meyerhof pathway,
after the scientist who
elucidated the pathway
25/03/2019 13
 If there is adequate oxygen, an
aerobic pathway is followed
and pyruvate enters the Krebs
cycle.
 If there is insufficient oxygen
available, the anaerobic
pathway is continued and
pyruvate undergoes a series of
reactions to produce lactic acid.
 Lactic acid then is the end-
product of glycolysis, and if
there were not some
mechanism for its removal, it
would accumulate in the
muscle cells & cause muscle
“crumps”.
25/03/2019 14
The Citric Acid Cycle
• Citric acid cycle: A series of biochemical reactions in which the acetyl
portion of acetyl CoA is oxidized to carbon dioxide and ATP and the
reduced coenzymes FADH2 and NADH are produced
• Takes place in the mitochondria
• Also known as tricarboxylic acid cycle (TCA) or Krebs cycle:
• – Named after Hans Krebs who elucidated this pathway
• Two important types of reactions:
• – Reduction of NAD+ and FAD to produce NADH and FADH2
• – Decarboxylation of citric acid to produce carbon dioxide
• The citric acid cycle also produces 2 ATP by substrate level phosphorylation
from GTP
25/03/2019 15
25/03/2019 16
The reactions of the cycle takes
place in the mitochondrial
matrix, except the succinate
dehydrogenase reaction that
involves FAD
The enzyme that catalyzes this
reaction is an integral part of
the inner mitochondrial
membrane
The “fuel “ for the cycle is
acetyl CoA, obtained from the
breakdown of carbohydrates,
fats, and proteins
– NADH acts as an inhibitor
– ADP as an activator
The Electron Transport Chain
 The electron transport chain (ETC) facilitates the passage of electrons
trapped in FADH2 and NADH during citric cycle
 ETC is a series of biochemical reactions in which intermediate carriers
(protein and non-protein) aid the transfer of electrons and hydrogen
ions from NADH and FADH2
 The ultimate receiver of electrons is molecular oxygen
 The electron transport (respiratory chain) gets its name from the fact
that electrons are transported to oxygen absorbed via respiration
 ETC is the sequence of reactions whereby the reduced forms of the
coenzymes are reoxidized, ultimately by O2
25/03/2019 17
The Electron Transport Chain
 The enzymes and electron carriers needed for the ETC are located along
inner mitochondrial membrane
 They are organized into four distinct protein complexes and two mobile
carriers
 The four protein complexes tightly bound to membrane:
 Complex 1: NADH-coenzyme Q reductase
 Complex II: Succinate-coenzyme Q reductase
 Complex III: Coenzyme Q - cytochrome C reductase
 Complex IV: Cytochrome C oxidase
 Two mobile electron carriers are:
 Coenzyme Q and cytochrome C
25/03/2019 18
25/03/2019 19
Complex I: NADH-Coenzyme Q
Reductase:
Facilitates transfer of electrons from
NADH to coenzyme Q
Complex II: Succinate-Coenzyme Q
Reductase
Succinate is converted to fumarate by this
Complex
In the process it generates FADH2
CoQ is the final recipient of the
electrons from FADH2
• Complex III: Coenzyme Q –Cytochrome c
Reductase
• Several iron-sulfur proteins and cytochromes
are electron carriers in this complex
• Cytochrome is a heme iron protein in which
reversible oxidation of an iron atom occurs
• Complex IV: Coenzyme Q –Cytochrome c
Reductase
• The electrons flow from cyt c to cyt a to cyt a3
• In the final stage of electron transfer, the
electrons from cyt a3, and hydrogen ion (H+)
combine with oxygen (O2) to form water
• O2 + 4H+ + 4e- 2 H2O
25/03/2019 20
Summary of the flow of electrons through four
complexes of the electron transport chain
25/03/2019 21
25/03/2019 22
Oxidative Phosphorylation
25/03/2019 23
Summary of the Common Metabolic Pathway
25/03/2019 24
ATP Production for the Complete Oxidation
of Glucose
25/03/2019 25
HEXOSE MONOPHOSPHATE SHUNT
Pentose Phosphate Pathway/Phosphogluconate Pathway
• 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
25/03/2019 26
HMP
25/03/2019 27
Significance of HMP Shunt
25/03/2019 28
Glycogenesis and Glycogenolysis
Involved in the regulation of blood glucose
concentration
When the dietary intake of glucose exceeds immediate
needs, humans and other animals can convert the excess
to glycogen, which is stored in either the liver or muscle
tissue.
Glycogenesis is the pathway that converts glucose into
glycogen.
When there’s need for additional blood glucose,
glycogen is hydrolyzed and released into the
bloodstream.
Glycogenolysis is the pathway that hydrolyzes glycogen
to glucose.
25/03/2019 29
25/03/2019 30
Gluconeogenesis
• Metabolic pathway by which glucose is synthesized from noncarbohydrate
sources:
– The process is not exact opposite of glycolysis
• Glycogen stores in muscle and liver tissue are depleted with in 12-18 hours
from fasting or in even less time from heavy work or strenuous physical
activity
• Without gluconeogenesis, the brain, which is dependent on glucose as a
fuel would have problems functioning if food intake were restricted for even
one day
25/03/2019 31
Importance of Gluconeogenesis
• Gluconeogenesis helps to maintain normal blood-glucose levels in times of
inadequate dietary carbohydrate intake
• About 90% of gluconeogenesis takes place in the liver
• Non-carbohydrate starting materials for gluconeogenesis:
– Pyruvate
– Lactate (from muscles and from red blood cells)
– Glycerol (from triacylglycerol hydrolysis)
– Certain amino acids (from dietary protein hydrolysis or from muscle protein
during starvation)
25/03/2019 32
Importance of Gluconeogenesis
25/03/2019 33
Gluconeogenesis
Cori cycle
• Lactate, formed from glucose under
anaerobic conditions in muscle cells
(glycolysis), is transferred to the
liver, where it is reconverted to
• Glucose (gluconeogenesis), which is
then transferred back to the muscle
cells.
25/03/2019 34
Relationships Among Four Common Metabolic Pathways That
Involve Glucose
25/03/2019 35
Regulation of Blood glucose
• Metabolic & hormonal mechanisms
• regulate blood glucose level
• Maintenance of stable levels of glucose in blood is by
Liver.
Extrahepatic tissues.
Hormones .
25/03/2019 36
Regulation of Blood glucose
25/03/2019 37
Blood Sugar and Its Regulation
Fate of Absorbed Glucose
1st Priority: glycogen storage
Stored in muscle and liver
2nd Priority: provide energy
Oxidized to ATP
3rd Priority: stored as fat
Only excess glucose
Stored as triglycerides in
adipose
25/03/2019 38
Regulation of Blood glucose
25/03/2019 39
Regulation of blood glucose levels
Insulin
25/03/2019 40
Role of glucagon
25/03/2019 41
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
Hyperthyroid
Fasting blood
glucose is elevated
Patients utilise
glucose at normal
or increased rate
25/03/2019 42
Glucocorticoids
Glucocorticoids are antagonistic
to insulin
Inhibit the utilisation of glucose
in extrahepatic tissues
Increased gluconeogenesis
Epinephrine
Secreted by adrenal medulla
It stimulates glycogenolysis in
liver & muscle
It diminishes the release of
insulin from pancreas
25/03/2019 43
Other 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 β-
cell exhaustion
Sex hormones
Estrogens cause increased liberation of insulin
Testosterone decrease blood sugar level
25/03/2019 44
Summary
All living organisms require energy for
their maintenance, growth, exercise
and reproduction
Most of this energy is provided by
carbohydrates
So carbohydrates are life line for living
organisms
That is why the carbohydrate
metabolism involve different complex
pathways for generation of energy
25/03/2019 45
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
25/03/2019 46

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Carbohydrate metabolism

  • 1. GUANGDONG OCEAN UNIVERSITY Carbohydrates Metabolism (糖代谢---táng dài xiè) Presenter: Muhammad Waseem (Ghani) Class: Advanced Biochemistry
  • 3. Overview CARBOHYDRATES: 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 25/03/2019 3
  • 5. Importance and functions of Carbohydrates Carbohydrates constitute the largest component of an average diet The most important function of carbohydrates is to provide energy Storage form of energy (starch and glycogen) Energy production from carbohydrates will be 4 k calories/g (16 k Joules/g). Excess carbohydrate is converted to fat. Some tissues, e.g. brain and erythrocytes, get energy almost exclusively from glucose If the conditions become anaerobic, only glucose can be used as a fuel 25/03/2019 5
  • 6. Importance and functions of Carbohydrates Ribose and deoxyribose are used to synthesize nucleotides and nucleic acids Some carbohydrates form the prosthetic group of hormones, immunoglobulins, blood group substances etc. Some carbohydrates act as structural constituents of tissues Structural basis of many organisms. For example, cellulose of plants, exoskeleton of insects etc. Glycoproteins and glycolipids are components of cell membranes and receptors. 25/03/2019 6
  • 7. Over view of Carbohydrate Metabolism The entire spectrum of chemical reactions, occurring in the living system are referred as “Metabolism” Types of metabolic pathways in cellular metabolism 1. Anabolic pathways: Protein synthesis. 2. Catabolic Pathways: Oxidative phosphorylation 3. Amphibolic pathways: Citric acid cycle. • Cells break down excess carbohydrates first, then lipids, finally amino acids if energy needs are not met by carbohydrates and fat • Nutrients not used for energy are used to build up structure, are stored, or excreted • 40% of the energy released in catabolism is captured in ATP, the rest is released as heat 25/03/2019 7
  • 8. Carbohydrate Metabolism • Primarily glucose Fructose and galactose enter the pathways at various points All cells can utilize glucose for energy production Glucose uptake from blood to cells usually mediated by insulin and transporters Liver is central site for carbohydrate metabolism Glucose uptake independent of insulin The only exporter of glucose 25/03/2019 8
  • 9. Digestion and Absorption of Carbohydrates 25/03/2019 9
  • 10. 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) 25/03/2019 10
  • 11. Metabolism There are six major metabolic pathways of glucose: 1) Glycogenesis 2) Glycogenolysis 3) Gluconeogenesis 4) Hexose monophosphate shunt 5) Glycolysis 6) Citric Acid Cycle 25/03/2019 11
  • 12. Glycolysis Glycolysis is defined as the sequence of reactions converting glucose (or glycogen) to pyruvate or lactate, with the production of ATP 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 25/03/2019 12
  • 13. • A series of reactions in the cytoplasm which converts glucose (C6) to two molecules of pyruvate (a C3 carboxylate), and ATP and NADH are produced. • Also called Embden- Meyerhof pathway, after the scientist who elucidated the pathway 25/03/2019 13
  • 14.  If there is adequate oxygen, an aerobic pathway is followed and pyruvate enters the Krebs cycle.  If there is insufficient oxygen available, the anaerobic pathway is continued and pyruvate undergoes a series of reactions to produce lactic acid.  Lactic acid then is the end- product of glycolysis, and if there were not some mechanism for its removal, it would accumulate in the muscle cells & cause muscle “crumps”. 25/03/2019 14
  • 15. The Citric Acid Cycle • Citric acid cycle: A series of biochemical reactions in which the acetyl portion of acetyl CoA is oxidized to carbon dioxide and ATP and the reduced coenzymes FADH2 and NADH are produced • Takes place in the mitochondria • Also known as tricarboxylic acid cycle (TCA) or Krebs cycle: • – Named after Hans Krebs who elucidated this pathway • Two important types of reactions: • – Reduction of NAD+ and FAD to produce NADH and FADH2 • – Decarboxylation of citric acid to produce carbon dioxide • The citric acid cycle also produces 2 ATP by substrate level phosphorylation from GTP 25/03/2019 15
  • 16. 25/03/2019 16 The reactions of the cycle takes place in the mitochondrial matrix, except the succinate dehydrogenase reaction that involves FAD The enzyme that catalyzes this reaction is an integral part of the inner mitochondrial membrane The “fuel “ for the cycle is acetyl CoA, obtained from the breakdown of carbohydrates, fats, and proteins – NADH acts as an inhibitor – ADP as an activator
  • 17. The Electron Transport Chain  The electron transport chain (ETC) facilitates the passage of electrons trapped in FADH2 and NADH during citric cycle  ETC is a series of biochemical reactions in which intermediate carriers (protein and non-protein) aid the transfer of electrons and hydrogen ions from NADH and FADH2  The ultimate receiver of electrons is molecular oxygen  The electron transport (respiratory chain) gets its name from the fact that electrons are transported to oxygen absorbed via respiration  ETC is the sequence of reactions whereby the reduced forms of the coenzymes are reoxidized, ultimately by O2 25/03/2019 17
  • 18. The Electron Transport Chain  The enzymes and electron carriers needed for the ETC are located along inner mitochondrial membrane  They are organized into four distinct protein complexes and two mobile carriers  The four protein complexes tightly bound to membrane:  Complex 1: NADH-coenzyme Q reductase  Complex II: Succinate-coenzyme Q reductase  Complex III: Coenzyme Q - cytochrome C reductase  Complex IV: Cytochrome C oxidase  Two mobile electron carriers are:  Coenzyme Q and cytochrome C 25/03/2019 18
  • 19. 25/03/2019 19 Complex I: NADH-Coenzyme Q Reductase: Facilitates transfer of electrons from NADH to coenzyme Q Complex II: Succinate-Coenzyme Q Reductase Succinate is converted to fumarate by this Complex In the process it generates FADH2 CoQ is the final recipient of the electrons from FADH2
  • 20. • Complex III: Coenzyme Q –Cytochrome c Reductase • Several iron-sulfur proteins and cytochromes are electron carriers in this complex • Cytochrome is a heme iron protein in which reversible oxidation of an iron atom occurs • Complex IV: Coenzyme Q –Cytochrome c Reductase • The electrons flow from cyt c to cyt a to cyt a3 • In the final stage of electron transfer, the electrons from cyt a3, and hydrogen ion (H+) combine with oxygen (O2) to form water • O2 + 4H+ + 4e- 2 H2O 25/03/2019 20
  • 21. Summary of the flow of electrons through four complexes of the electron transport chain 25/03/2019 21
  • 24. Summary of the Common Metabolic Pathway 25/03/2019 24
  • 25. ATP Production for the Complete Oxidation of Glucose 25/03/2019 25
  • 26. HEXOSE MONOPHOSPHATE SHUNT Pentose Phosphate Pathway/Phosphogluconate Pathway • 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 25/03/2019 26
  • 28. Significance of HMP Shunt 25/03/2019 28
  • 29. Glycogenesis and Glycogenolysis Involved in the regulation of blood glucose concentration When the dietary intake of glucose exceeds immediate needs, humans and other animals can convert the excess to glycogen, which is stored in either the liver or muscle tissue. Glycogenesis is the pathway that converts glucose into glycogen. When there’s need for additional blood glucose, glycogen is hydrolyzed and released into the bloodstream. Glycogenolysis is the pathway that hydrolyzes glycogen to glucose. 25/03/2019 29
  • 31. Gluconeogenesis • Metabolic pathway by which glucose is synthesized from noncarbohydrate sources: – The process is not exact opposite of glycolysis • Glycogen stores in muscle and liver tissue are depleted with in 12-18 hours from fasting or in even less time from heavy work or strenuous physical activity • Without gluconeogenesis, the brain, which is dependent on glucose as a fuel would have problems functioning if food intake were restricted for even one day 25/03/2019 31
  • 32. Importance of Gluconeogenesis • Gluconeogenesis helps to maintain normal blood-glucose levels in times of inadequate dietary carbohydrate intake • About 90% of gluconeogenesis takes place in the liver • Non-carbohydrate starting materials for gluconeogenesis: – Pyruvate – Lactate (from muscles and from red blood cells) – Glycerol (from triacylglycerol hydrolysis) – Certain amino acids (from dietary protein hydrolysis or from muscle protein during starvation) 25/03/2019 32
  • 34. Gluconeogenesis Cori cycle • Lactate, formed from glucose under anaerobic conditions in muscle cells (glycolysis), is transferred to the liver, where it is reconverted to • Glucose (gluconeogenesis), which is then transferred back to the muscle cells. 25/03/2019 34
  • 35. Relationships Among Four Common Metabolic Pathways That Involve Glucose 25/03/2019 35
  • 36. Regulation of Blood glucose • Metabolic & hormonal mechanisms • regulate blood glucose level • Maintenance of stable levels of glucose in blood is by Liver. Extrahepatic tissues. Hormones . 25/03/2019 36
  • 37. Regulation of Blood glucose 25/03/2019 37
  • 38. Blood Sugar and Its Regulation Fate of Absorbed Glucose 1st Priority: glycogen storage Stored in muscle and liver 2nd Priority: provide energy Oxidized to ATP 3rd Priority: stored as fat Only excess glucose Stored as triglycerides in adipose 25/03/2019 38
  • 39. Regulation of Blood glucose 25/03/2019 39
  • 40. Regulation of blood glucose levels Insulin 25/03/2019 40
  • 42. 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 Hyperthyroid Fasting blood glucose is elevated Patients utilise glucose at normal or increased rate 25/03/2019 42
  • 43. Glucocorticoids Glucocorticoids are antagonistic to insulin Inhibit the utilisation of glucose in extrahepatic tissues Increased gluconeogenesis Epinephrine Secreted by adrenal medulla It stimulates glycogenolysis in liver & muscle It diminishes the release of insulin from pancreas 25/03/2019 43
  • 44. Other 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 β- cell exhaustion Sex hormones Estrogens cause increased liberation of insulin Testosterone decrease blood sugar level 25/03/2019 44
  • 45. Summary All living organisms require energy for their maintenance, growth, exercise and reproduction Most of this energy is provided by carbohydrates So carbohydrates are life line for living organisms That is why the carbohydrate metabolism involve different complex pathways for generation of energy 25/03/2019 45
  • 46. 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 25/03/2019 46