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Nursing - 5

Introduction to carbohydrates
       and Glycolysis
Function of carbohydrates
• Carbohydrates are the most abundant organic
  molecules in nature
• providing a significant fraction of the energy in the
  diet of most organisms.
• Acting as a storage form of energy in the body.
• Serving as cell membrane components that
  mediate some forms of intercellular
  communication.
• Serve as a structural component of many
  organisms, including the cell walls of bacteria, the
  exoskeleton of many insects, and the fibrous
  cellulose of plants.
  2
CLASSIFICATION
Carbohydrates are classified into three main groups:
• 1) Monosaccharides (simple sugars) : They consist of a
single polyhydroxyaldehyde(glucose) or ketone units
(fructose). They can not be hydrolysed into simpler
units. The sugar unit is sometimes referred to as
glycan.
• 2) Oligosaccharides (oligo= few) : contain from two to
ten monosaccharide units joined in glycosidic bonds.
e.g. disaccharides (2 units) e.g. maltose and sucrose,
trisaccharides(3 units).....etc.
• 3) Polysaccharides (poly = many): Also known as glycans.
They are composed of more than ten monosaccharide
units e.g. starch, glycogen, cellulose.....etc.
   3
Monosaccharides
• They have the common formula
  (CH2O)n, where n = 3 or some larger
  number




 4
• Isomers, epimers and enantiomers:
• Compounds that have the same chemical formula but have
  different structures are called isomers. Eg. fructose,
  glucose, mannose, and galactose are all isomers.
• two monosaccharides differ in configuration around only
  one specific carbon atom, they are defined as epimers of
  each other. Eg. glucose and galactose are C-4 epimers.
• A special type of isomerism is found in the pairs of
  structures that are mirror images of each other.
• These mirror images are called enantiomers, and the two
  members of the pair are designated as a D- and an L-sugar.
• The vast majority of the sugars in humans are D-sugars.

  5
6
Galactose




7
CLASSIFICATION OF
          MONOSACCHARIDES
• Can be carried out by one of two methods:
  1) According to the number of carbon atoms :
  Trioses, Tetroses, Pentoses,
  Hexoses, Heptoses, Octoses.




8
• 2) According to the characteristic carbonyl group:
Aldehyde group or ketone group
     a) Aldo sugars: Aldoses :
Monosaccharides containing aldehyde group e.g. glucose,
  ribose.
      b) Keto sugars: Ketoses :
Monosaccharides containing ketone group e.g. fructose,
  ribulose.




   9
Complex carbohydrates
• Carbohydrates can be attached by glycosidic bonds
  to non-carbohydrate structures, including:
• purines and pyrimidines (found in nucleic acids),
• aromatic rings (such as those found in steroids
  and bilirubin),
• proteins (found in glycoproteins and glycos-
  aminoglycans)
• lipids (found in glycolipids).


  10
A. Digestion of carbohydrates begins in
                the mouth
• The major dietary polysaccharides are of animal
  (glycogen) and plant origin (starch, composed of
  amylose and amylopectin).
• During mastication, salivary α-amylase acts briefly
  on dietary starch in a random manner, breaking
  some α(1- 4) bonds.
• Because branched amylopectin and glycogen also
  contain α(1- 6) bonds, the digest resulting from the
  action of α-amylase contains a mixture of smaller,
  branched oligosaccharide molecules.
  11
12
• Carbohydrate digestion halts temporarily in the
  stomach, because the high acidity inactivates
  the salivary α-amylase.

• Note: There are both α(1- 4) and β(1- 4)-
  endoglucosidases in nature, but humans do
  not produce and secrete the latter in digestive
  juices. Therefore,
•    they are unable to digest cellulose—a
  carbohydrate of plant origin containing β(1- 4)
  glycosidic bonds between glucose residues.
13
B. Further digestion of carbohydrates
 by pancreatic enzymes occurs in the
             small intestine

• When the acidic stomach contents reach
  the small intestine, they are neutralized by
  bicarbonate secreted by the pancreas, and
  pancreatic α-amylase continues the
  process of starch digestion.


 14
• C- Digestion by intestinal enzymes:
• The final digestive processes occur at the mucosal
  lining of upper jejunum by enzymes synthesized
  by the intestinal mucosal cells.
• Brush borders intestinal enzymes are:
• 1- Oligo 1,6 glucosidase releases glucose residues
  from branched oligosaccharides.
• 2- disaccharidasess
• - Sucrase converts sucrose to glucose and
  fructose.
• - Lactase converts lactose to glucose and
  galactose.
• - Maltase converts maltose to two glucose
  molecules
  15
D. Absorption of monosaccharides by
              intestinal mucosal cells
• The duodenum and upper jejunum absorb the bulk
  of the dietary sugars.
• Insulin is not required for the uptake of glucose by
  intestinal cells.
• However, different sugars have different
  mechanisms of absorption.
1. galactose and glucose are transported into the
mucosal cells by an active, energy-requiring process
that involves a specific transport protein and requires
a concurrent uptake of sodium ions.
  16
2. Fructose uptake requires a sodium-
independent monosaccharide transporter
(GLUT-5) for its absorption.
3. All three monosaccharides are
transported from the intestinal mucosal cell
into the portal circulation by yet another
transporter, GLUT-2.



17
Glucose metabolism
Importance of Glucose:
1. Glucose is the preferred source of energy for most
   of the body tissues. Brain cells derive energy
   mainly from glucose.
2. When glucose metabolism is deranged, life-
   threatenung conditions may occur. A minimum
   amount of glucose is always required for normal
   functioning.
3. Normal fasting plasma glucose level is 70 to 110
   mg/dl. After a heavy carbohydrate meal, in a
   normal person, this level is below 150 mg/dl.
  18
• Glucose is used in:
• Oxidation:
• The pathways for oxidation of glucose are classified
  into two main groups:
•     A. The major pathways which are mainly for
  energy production:
•       1. Glycolysis.
•       2. Citric acid cycle (CAC).
• B. The minor pathways for oxidation which are
  not for energy production:
•       1. Hexose monophosphate shunt (HMS).
•       2. Uronic acid pathway.
  19
• II. Conversion to biologically active
  substances as:
• 1. Galactose: which is essential for formation
  of lactose, glycolipids, mucopolysaccharides,
  ...etc.
• 2. Fructose: needed for nutrition of sperms.
• 3. Amino sugars.
• 4. Non-essential amino acids.
• 5. Fatty acids.
• 6. Ribose-5-P.
• 7. Glucuronic acid.
  20
• III. Storage of glucose:
• 1. As glycogen in the liver and muscles mainly.
• 2. As triglycerides (TG), mainly in adipose
  tissues.

• IV. Excretion of glucose in urine:
• When blood glucose level exceeds a certain
  limit (renal sugar threshold), it will pass to
  urine. This will occur when blood glucose level
  is above 180 mg/dl and this is known as
  glucosuria.
21
Glycolysis
      (Embden Meyerhof Pathway)
Definition:
•      It is degradation of glucose to generate ATP and
   to provide intermediates for other synthetic and
   metabolic pathways. Aerobically it ends with
   pyruvate while anaerobically lactate is the end
   product.
 Site of glycolysis:
•      It occurs in the cell cytosol of all tissues.

    22
Glycolysis
       (Embden-Meyerhof Pathway)
Importance of the pathway
• In this pathway glucose is converted to pyruvate
  (aerobic condition) or lactate (anaeroboic
  condition), along with production of a small
  quantity of energy.
• Glycolysis is the only source of energy in
  erythrocytes.


  23
• In strenuous exercise, when muscle tissue
  lacks enough oxygen, anaerobic glycolysis
  forms the major source of energy for muscles.
• The glycolytic pathway may be considered as
  the preliminary step before complete
  oxidation.
• The glycolytic pathway also provides carbon
  skeleton for synthesis of certain nonessential
  amino acids as well as glycerol part of fat.
• Most of the reactions of the glycolytic
  pathway are reversible, which are also used
  24
  for gluconeogenesis.
• Steps of glycolysis:
• Conversion of glucose to G-6-P, is irreversible
  (non-equilibrium reaction). It is catalyzed by
  glucokinase (in liver and pancreas) or by
  hexokinase (in all other tissues).
• Aldolase A: (F1,6 diphosphate aldolase) Occurs
  in most tissues.
  Two molecules of ATP are liberated in each
  step since every molecule of glucose gives rise
  to two trioses.

25
26
27
Energy production
1. Under aerobic conditions:
     Glucose ------→ 2 Pyruvate + 8 ATP.
  For tissues that have mitochondria,
  glycolysis is considered a preparatory
  step for complete oxidation via citric acid
  cycle since pyruvate is transported into
  the mitochondria to provide oxaloacetate
  or active acetate where it is oxidized by
  citric acid cycle for more energy.
  28
• The hydrogens of NADH produced by
  glycolysis are transported to the mitochondria
  mainly to be oxidized by electron transport
  chain (ETC).

• 2. Under anaerobic conditions:

 Glucose ------→ 2 lactate + 2 ATP
 Pyruvate is reduced to lactate in a reversible
  reaction catalyzed by lactate dehydrogenase
  (LDH).
  29
• This occurs in muscles during severe exercise
  (hypoxic conditions) and in tissues that lack
  mitochondria as RBCs and lens.
30
Cori’s cycle or lactic acid cycle
• In an actively contracting muscle, only about
  8% of the pyruvate is utilized by the citric acid
  cycle, and the remaining molecules are
  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 through to
  be due to lactate accumulation.

31
32
Regulation of glycolysis
       Hormonal regulation of glycolysis:
• a) Glucagon : is secreted in hypoglycemia or in
   carbohydrate deficiency. It affects liver cells mainly
   as follows:
  It acts as inhibitors for glycolytic key enzymes
   (glucokinase,PFK-1, pyruvate kinase).

• b) Insulin: It is secreted in hyperglycemia and after
  carbohydrates feeding, it causes:
  Stimulation of glycolytic key enzymes.
  33
Inhibitors of glycolysis:
1- 2- deoxyglucose inhibits
  hexokinase.
2- Mercury and iodoacetate inhibit
   glyceraldehyde-3-P dehydrogenase.
3- Fluoride inhibits enolase by
  removal of Mg2+ as Mg fluoride.

34

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Lec 5 level 3-nu(carbohydrate metabolism i)

  • 1. Nursing - 5 Introduction to carbohydrates and Glycolysis
  • 2. Function of carbohydrates • Carbohydrates are the most abundant organic molecules in nature • providing a significant fraction of the energy in the diet of most organisms. • Acting as a storage form of energy in the body. • Serving as cell membrane components that mediate some forms of intercellular communication. • Serve as a structural component of many organisms, including the cell walls of bacteria, the exoskeleton of many insects, and the fibrous cellulose of plants. 2
  • 3. CLASSIFICATION Carbohydrates are classified into three main groups: • 1) Monosaccharides (simple sugars) : They consist of a single polyhydroxyaldehyde(glucose) or ketone units (fructose). They can not be hydrolysed into simpler units. The sugar unit is sometimes referred to as glycan. • 2) Oligosaccharides (oligo= few) : contain from two to ten monosaccharide units joined in glycosidic bonds. e.g. disaccharides (2 units) e.g. maltose and sucrose, trisaccharides(3 units).....etc. • 3) Polysaccharides (poly = many): Also known as glycans. They are composed of more than ten monosaccharide units e.g. starch, glycogen, cellulose.....etc. 3
  • 4. Monosaccharides • They have the common formula (CH2O)n, where n = 3 or some larger number 4
  • 5. • Isomers, epimers and enantiomers: • Compounds that have the same chemical formula but have different structures are called isomers. Eg. fructose, glucose, mannose, and galactose are all isomers. • two monosaccharides differ in configuration around only one specific carbon atom, they are defined as epimers of each other. Eg. glucose and galactose are C-4 epimers. • A special type of isomerism is found in the pairs of structures that are mirror images of each other. • These mirror images are called enantiomers, and the two members of the pair are designated as a D- and an L-sugar. • The vast majority of the sugars in humans are D-sugars. 5
  • 6. 6
  • 8. CLASSIFICATION OF MONOSACCHARIDES • Can be carried out by one of two methods: 1) According to the number of carbon atoms : Trioses, Tetroses, Pentoses, Hexoses, Heptoses, Octoses. 8
  • 9. • 2) According to the characteristic carbonyl group: Aldehyde group or ketone group a) Aldo sugars: Aldoses : Monosaccharides containing aldehyde group e.g. glucose, ribose. b) Keto sugars: Ketoses : Monosaccharides containing ketone group e.g. fructose, ribulose. 9
  • 10. Complex carbohydrates • Carbohydrates can be attached by glycosidic bonds to non-carbohydrate structures, including: • purines and pyrimidines (found in nucleic acids), • aromatic rings (such as those found in steroids and bilirubin), • proteins (found in glycoproteins and glycos- aminoglycans) • lipids (found in glycolipids). 10
  • 11. A. Digestion of carbohydrates begins in the mouth • The major dietary polysaccharides are of animal (glycogen) and plant origin (starch, composed of amylose and amylopectin). • During mastication, salivary α-amylase acts briefly on dietary starch in a random manner, breaking some α(1- 4) bonds. • Because branched amylopectin and glycogen also contain α(1- 6) bonds, the digest resulting from the action of α-amylase contains a mixture of smaller, branched oligosaccharide molecules. 11
  • 12. 12
  • 13. • Carbohydrate digestion halts temporarily in the stomach, because the high acidity inactivates the salivary α-amylase. • Note: There are both α(1- 4) and β(1- 4)- endoglucosidases in nature, but humans do not produce and secrete the latter in digestive juices. Therefore, • they are unable to digest cellulose—a carbohydrate of plant origin containing β(1- 4) glycosidic bonds between glucose residues. 13
  • 14. B. Further digestion of carbohydrates by pancreatic enzymes occurs in the small intestine • When the acidic stomach contents reach the small intestine, they are neutralized by bicarbonate secreted by the pancreas, and pancreatic α-amylase continues the process of starch digestion. 14
  • 15. • C- Digestion by intestinal enzymes: • The final digestive processes occur at the mucosal lining of upper jejunum by enzymes synthesized by the intestinal mucosal cells. • Brush borders intestinal enzymes are: • 1- Oligo 1,6 glucosidase releases glucose residues from branched oligosaccharides. • 2- disaccharidasess • - Sucrase converts sucrose to glucose and fructose. • - Lactase converts lactose to glucose and galactose. • - Maltase converts maltose to two glucose molecules 15
  • 16. D. Absorption of monosaccharides by intestinal mucosal cells • The duodenum and upper jejunum absorb the bulk of the dietary sugars. • Insulin is not required for the uptake of glucose by intestinal cells. • However, different sugars have different mechanisms of absorption. 1. galactose and glucose are transported into the mucosal cells by an active, energy-requiring process that involves a specific transport protein and requires a concurrent uptake of sodium ions. 16
  • 17. 2. Fructose uptake requires a sodium- independent monosaccharide transporter (GLUT-5) for its absorption. 3. All three monosaccharides are transported from the intestinal mucosal cell into the portal circulation by yet another transporter, GLUT-2. 17
  • 18. Glucose metabolism Importance of Glucose: 1. Glucose is the preferred source of energy for most of the body tissues. Brain cells derive energy mainly from glucose. 2. When glucose metabolism is deranged, life- threatenung conditions may occur. A minimum amount of glucose is always required for normal functioning. 3. Normal fasting plasma glucose level is 70 to 110 mg/dl. After a heavy carbohydrate meal, in a normal person, this level is below 150 mg/dl. 18
  • 19. • Glucose is used in: • Oxidation: • The pathways for oxidation of glucose are classified into two main groups: • A. The major pathways which are mainly for energy production: • 1. Glycolysis. • 2. Citric acid cycle (CAC). • B. The minor pathways for oxidation which are not for energy production: • 1. Hexose monophosphate shunt (HMS). • 2. Uronic acid pathway. 19
  • 20. • II. Conversion to biologically active substances as: • 1. Galactose: which is essential for formation of lactose, glycolipids, mucopolysaccharides, ...etc. • 2. Fructose: needed for nutrition of sperms. • 3. Amino sugars. • 4. Non-essential amino acids. • 5. Fatty acids. • 6. Ribose-5-P. • 7. Glucuronic acid. 20
  • 21. • III. Storage of glucose: • 1. As glycogen in the liver and muscles mainly. • 2. As triglycerides (TG), mainly in adipose tissues. • IV. Excretion of glucose in urine: • When blood glucose level exceeds a certain limit (renal sugar threshold), it will pass to urine. This will occur when blood glucose level is above 180 mg/dl and this is known as glucosuria. 21
  • 22. Glycolysis (Embden Meyerhof Pathway) Definition: • It is degradation of glucose to generate ATP and to provide intermediates for other synthetic and metabolic pathways. Aerobically it ends with pyruvate while anaerobically lactate is the end product. Site of glycolysis: • It occurs in the cell cytosol of all tissues. 22
  • 23. Glycolysis (Embden-Meyerhof Pathway) Importance of the pathway • In this pathway glucose is converted to pyruvate (aerobic condition) or lactate (anaeroboic condition), along with production of a small quantity of energy. • Glycolysis is the only source of energy in erythrocytes. 23
  • 24. • In strenuous exercise, when muscle tissue lacks enough oxygen, anaerobic glycolysis forms the major source of energy for muscles. • The glycolytic pathway may be considered as the preliminary step before complete oxidation. • The glycolytic pathway also provides carbon skeleton for synthesis of certain nonessential amino acids as well as glycerol part of fat. • Most of the reactions of the glycolytic pathway are reversible, which are also used 24 for gluconeogenesis.
  • 25. • Steps of glycolysis: • Conversion of glucose to G-6-P, is irreversible (non-equilibrium reaction). It is catalyzed by glucokinase (in liver and pancreas) or by hexokinase (in all other tissues). • Aldolase A: (F1,6 diphosphate aldolase) Occurs in most tissues. Two molecules of ATP are liberated in each step since every molecule of glucose gives rise to two trioses. 25
  • 26. 26
  • 27. 27
  • 28. Energy production 1. Under aerobic conditions: Glucose ------→ 2 Pyruvate + 8 ATP. For tissues that have mitochondria, glycolysis is considered a preparatory step for complete oxidation via citric acid cycle since pyruvate is transported into the mitochondria to provide oxaloacetate or active acetate where it is oxidized by citric acid cycle for more energy. 28
  • 29. • The hydrogens of NADH produced by glycolysis are transported to the mitochondria mainly to be oxidized by electron transport chain (ETC). • 2. Under anaerobic conditions: Glucose ------→ 2 lactate + 2 ATP Pyruvate is reduced to lactate in a reversible reaction catalyzed by lactate dehydrogenase (LDH). 29
  • 30. • This occurs in muscles during severe exercise (hypoxic conditions) and in tissues that lack mitochondria as RBCs and lens. 30
  • 31. Cori’s cycle or lactic acid cycle • In an actively contracting muscle, only about 8% of the pyruvate is utilized by the citric acid cycle, and the remaining molecules are 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 through to be due to lactate accumulation. 31
  • 32. 32
  • 33. Regulation of glycolysis Hormonal regulation of glycolysis: • a) Glucagon : is secreted in hypoglycemia or in carbohydrate deficiency. It affects liver cells mainly as follows: It acts as inhibitors for glycolytic key enzymes (glucokinase,PFK-1, pyruvate kinase). • b) Insulin: It is secreted in hyperglycemia and after carbohydrates feeding, it causes: Stimulation of glycolytic key enzymes. 33
  • 34. Inhibitors of glycolysis: 1- 2- deoxyglucose inhibits hexokinase. 2- Mercury and iodoacetate inhibit glyceraldehyde-3-P dehydrogenase. 3- Fluoride inhibits enolase by removal of Mg2+ as Mg fluoride. 34