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Carbohydrate
Metabolism
Carbohydrate Metabolism - Biochemistry
Absorption of Monosaccharides
1- Simple Diffusion
• According to concentration gradient.
• Fructose & pentoses.
2- Facilitated Transport
GLUT5: glucose, galactose & fructose.
3- Active Transport
Sodium glucose transporter (SGLT)I: glucose & galactose.
Fate of Absorbed Sugars
• Absorbed Fructose and galactose liver glucose
uptake by tissues
Pathways for glucose utilization
1- Oxidation for production of energy
2- Provides other compounds:
Carbohydrates: i.e. fructose, galactose & pentoses.
Glycerol 3-phosphate: triacylglycerol and phospholipids
Acetyl CoA: cholesterol and fatty acids
Non essential amino acids.
3- Storage: glycogen in liver & triacylglycerol in adipose tissue.
4- Excretion in urine.
Oxidation of glucose
I- The Major Pathways: for energy production.
A) Glycolysis: produces pyruvate under aerobic condition
lactate under anaerobic condition.
B) Krebs’ cycle: under aerobic condition, pyruvate is
converted to active acetate for oxidation through Krebs’ cycle.
II- The Minor Pathways: for synthesis of other derivatives.
A) Hexose monophosphate pathway (HMP): For
production of pentoses and NADPH.
B) Uronic acid pathway: For production of uronic
acids.
GLYCOLYSIS
• Oxidation of glucose to pyruvate in presence of O2 or lactate
in absence of O2.
• Site: cytosol of all cells.
• Steps:
Phase I (Energy utilization phase):
Glucose is cleaved to two molecules of glyceraldehyde 3-phosphate.
This phase consumes 2 molecules of ATP.
Phase II (Energy recovery phase):
The two molecules of glyceraldehyde 3-phosphate are converted to
pyruvate under aerobic state with generation of 10 ATPs.
Or lactate under anaerobic state with generation of 4 ATPs.
- All reactions are reversible except GK, PFK, PK.
Hexokinase Glucokinase
Site Extrahepatic Liver & pancreatic β cells
Km Low (high affinity) High (low affinity)
G6P Allosteric inhibitor No effect
Glucagon No effect Inhibitor
Insulin No effect Stimulator
Carbohydrate Metabolism - Biochemistry
Importance of Glycolysis
I. Energy production
Reaction catalyzed by Aerobic state Anaerobic state
Hexokinase or Glucokinase -1 -1
Phosphofructokinase-1
-1 -1
Glyceraldehyde 3-
phosphate dehydrogenase
+6 0
Phosphoglycerate kinase +2 +2
Pyruvate kinase
+2 +2
Net energy gain 8 ATP 2 ATP
II. Importance of Intermediates
Pyruvate: active acetate, oxaloacetate, and lactate.
DHAP glycerol 3-phosphate which is used in
triacylglycerol and phospholipid synthesis.
Non essential aa : Pyruvate alanine
3Phosphoglycerate serine.
Regulation
Key enzymes: GK, PFK, PK
Stimulated by: insulin, AMP, F6P
Inhibited by: glucagon, ATP, citrate
Carbohydrate Metabolism - Biochemistry
Energy Yield from Glucose Oxidation
Pathway Products ATP
Glycolysis 2 X pyruvate 8
Oxidative decarboxylation
of pyruvate
2 X Acetyl CoA 2 x 3 = 6
TCA, ETC 2 x 12 = 24
Net energy gain 38
Hexose Monophosphate Pathway
(HMP)
alternative route for glucose oxidation not for energy production.
• Site: cytosol of liver, adipose tissue, ovaries, testes, RBCs &
retina.
• Steps:
Oxidative irreversible phase:
Glucose 6-phosphate undergoes dehydrogenation &
decarboxylation to yield ribulose 5-phosphate.
Nonoxidative reversible phase:
6 molecules of ribulose 5-P are converted to 5 molecules of
glucose 6-P by two enzymes: transketolase & transaldolase.
Importance of HMP pathway
I- It provides ribose 5-phosphate
required for synthesis of nucleotides and nucleic acids.
II- Main source of NADPH, required for:
A) Reductases
1. Glutathione reductase
2. Folate, retinal reducatase
3. Reducatases of FA, steroid synthesis.
B) Hydroxylases
e.g. Steroids hydroxylase
C) NADPH Oxidase: phagocytosis (respiratory burst).
Favism
Genetic deficiency of glucose-6-phosphate dehydrogenase (G6PD).
• Precipitating factors:
Certain drugs (premaquine, aspirin), Fava beans
• Symptoms:
Asymptomatic: in between attacks.
Hemolytic crisis: on exposure to above factors.
• Mechanism:
G6PD deficiency HMP inhibition NADPH
Inhibition of glutathione reductase reduced glutathione
failure to protect cells from oxidative damage by H2O2
Lysis of red cells hemolytic anemia, jaundice.
• Managment:
- Avoid drugs, fava beans. - Blood transfusion during attacks
Uronic acid Pathway
is an alternative route for glucose oxidation.
• Site: cytosol of liver
Importance of Uronic acid pathway:
• Main function is formation of UDP-glucuronate:
1- Glycosaminoglycans (GAGs) synthesis.
2- Synthesis of L-ascorbic acid (not in human)
3- Conjugation reactions: with bilirubin, steroids to make them:
more soluble, easily excreted i.e. Detoxication.
GLUCONEOGENESIS
It is the synthesis of glucose and /or glycogen from non-
carbohydrate sources.
Site: Liver, kidney.
Steps: reversal of glycolysis, the irreversible reactions are
reversed by 4 enzymes:
Glycolytic Key Enzymes Gluconeogenic Key Enzymes
Glucokinase Glucose 6-phosphatase
Phosphofructokinase-1 Fructose 1,6-bisphosphatase
Pyruvate kinase Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase.
Sources:
1. Lactate.
2. Pyruvate.
3. Glucogenic aa
4. Glycerol
5. Odd chain FA
Regulation:
Insulin: gluconeogenesis, glycolysis
Anti-insulin: gluconeogenesis, glycolysis
Importance:
1. Source of blood glucose during fasting & starvation.
2. Removal of waste products e.g. lactate, glycerol.
Glycogen Metabolism
Glycogenesis
Definition: synthesis of glycogen from glucose.
Site: cytosol of liver & muscles.
Steps:
Carbohydrate Metabolism - Biochemistry
Carbohydrate Metabolism - Biochemistry
Glycogenolysis
Definition: breakdown of glycogen to glucose in liver or G6P in
muscles ( due to absence of G6 phosphatase in muscles).
Importance:
In muscles: source of energy during exercise.
In liver: source of blood glucose during 18 hours starvation.
Steps:
Carbohydrate Metabolism - Biochemistry
Von Gierke’s disease
Genetic disease due to deficiency of G6 phosphatase
Accumulation of glycogen in liver& kidney
Hepatomegaly, renal failure & fasting hypoglycemia.
G6P HMP PRPP
Purine nucleotide Uric acid
Hyperuricemia (Gout).
Carbohydrate Metabolism - Biochemistry

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Carbohydrate Metabolism - Biochemistry

  • 3. Absorption of Monosaccharides 1- Simple Diffusion • According to concentration gradient. • Fructose & pentoses. 2- Facilitated Transport GLUT5: glucose, galactose & fructose. 3- Active Transport Sodium glucose transporter (SGLT)I: glucose & galactose.
  • 4. Fate of Absorbed Sugars • Absorbed Fructose and galactose liver glucose uptake by tissues Pathways for glucose utilization 1- Oxidation for production of energy 2- Provides other compounds: Carbohydrates: i.e. fructose, galactose & pentoses. Glycerol 3-phosphate: triacylglycerol and phospholipids Acetyl CoA: cholesterol and fatty acids Non essential amino acids. 3- Storage: glycogen in liver & triacylglycerol in adipose tissue. 4- Excretion in urine.
  • 5. Oxidation of glucose I- The Major Pathways: for energy production. A) Glycolysis: produces pyruvate under aerobic condition lactate under anaerobic condition. B) Krebs’ cycle: under aerobic condition, pyruvate is converted to active acetate for oxidation through Krebs’ cycle. II- The Minor Pathways: for synthesis of other derivatives. A) Hexose monophosphate pathway (HMP): For production of pentoses and NADPH. B) Uronic acid pathway: For production of uronic acids.
  • 6. GLYCOLYSIS • Oxidation of glucose to pyruvate in presence of O2 or lactate in absence of O2. • Site: cytosol of all cells. • Steps: Phase I (Energy utilization phase): Glucose is cleaved to two molecules of glyceraldehyde 3-phosphate. This phase consumes 2 molecules of ATP. Phase II (Energy recovery phase): The two molecules of glyceraldehyde 3-phosphate are converted to pyruvate under aerobic state with generation of 10 ATPs. Or lactate under anaerobic state with generation of 4 ATPs. - All reactions are reversible except GK, PFK, PK.
  • 7. Hexokinase Glucokinase Site Extrahepatic Liver & pancreatic β cells Km Low (high affinity) High (low affinity) G6P Allosteric inhibitor No effect Glucagon No effect Inhibitor Insulin No effect Stimulator
  • 9. Importance of Glycolysis I. Energy production Reaction catalyzed by Aerobic state Anaerobic state Hexokinase or Glucokinase -1 -1 Phosphofructokinase-1 -1 -1 Glyceraldehyde 3- phosphate dehydrogenase +6 0 Phosphoglycerate kinase +2 +2 Pyruvate kinase +2 +2 Net energy gain 8 ATP 2 ATP
  • 10. II. Importance of Intermediates Pyruvate: active acetate, oxaloacetate, and lactate. DHAP glycerol 3-phosphate which is used in triacylglycerol and phospholipid synthesis. Non essential aa : Pyruvate alanine 3Phosphoglycerate serine. Regulation Key enzymes: GK, PFK, PK Stimulated by: insulin, AMP, F6P Inhibited by: glucagon, ATP, citrate
  • 12. Energy Yield from Glucose Oxidation Pathway Products ATP Glycolysis 2 X pyruvate 8 Oxidative decarboxylation of pyruvate 2 X Acetyl CoA 2 x 3 = 6 TCA, ETC 2 x 12 = 24 Net energy gain 38
  • 13. Hexose Monophosphate Pathway (HMP) alternative route for glucose oxidation not for energy production. • Site: cytosol of liver, adipose tissue, ovaries, testes, RBCs & retina. • Steps: Oxidative irreversible phase: Glucose 6-phosphate undergoes dehydrogenation & decarboxylation to yield ribulose 5-phosphate. Nonoxidative reversible phase: 6 molecules of ribulose 5-P are converted to 5 molecules of glucose 6-P by two enzymes: transketolase & transaldolase.
  • 14. Importance of HMP pathway I- It provides ribose 5-phosphate required for synthesis of nucleotides and nucleic acids. II- Main source of NADPH, required for: A) Reductases 1. Glutathione reductase
  • 15. 2. Folate, retinal reducatase 3. Reducatases of FA, steroid synthesis. B) Hydroxylases e.g. Steroids hydroxylase C) NADPH Oxidase: phagocytosis (respiratory burst).
  • 16. Favism Genetic deficiency of glucose-6-phosphate dehydrogenase (G6PD). • Precipitating factors: Certain drugs (premaquine, aspirin), Fava beans • Symptoms: Asymptomatic: in between attacks. Hemolytic crisis: on exposure to above factors. • Mechanism: G6PD deficiency HMP inhibition NADPH Inhibition of glutathione reductase reduced glutathione failure to protect cells from oxidative damage by H2O2 Lysis of red cells hemolytic anemia, jaundice. • Managment: - Avoid drugs, fava beans. - Blood transfusion during attacks
  • 17. Uronic acid Pathway is an alternative route for glucose oxidation. • Site: cytosol of liver Importance of Uronic acid pathway: • Main function is formation of UDP-glucuronate: 1- Glycosaminoglycans (GAGs) synthesis. 2- Synthesis of L-ascorbic acid (not in human) 3- Conjugation reactions: with bilirubin, steroids to make them: more soluble, easily excreted i.e. Detoxication.
  • 18. GLUCONEOGENESIS It is the synthesis of glucose and /or glycogen from non- carbohydrate sources. Site: Liver, kidney. Steps: reversal of glycolysis, the irreversible reactions are reversed by 4 enzymes: Glycolytic Key Enzymes Gluconeogenic Key Enzymes Glucokinase Glucose 6-phosphatase Phosphofructokinase-1 Fructose 1,6-bisphosphatase Pyruvate kinase Pyruvate carboxylase Phosphoenolpyruvate carboxykinase.
  • 19. Sources: 1. Lactate. 2. Pyruvate. 3. Glucogenic aa 4. Glycerol 5. Odd chain FA Regulation: Insulin: gluconeogenesis, glycolysis Anti-insulin: gluconeogenesis, glycolysis Importance: 1. Source of blood glucose during fasting & starvation. 2. Removal of waste products e.g. lactate, glycerol.
  • 20. Glycogen Metabolism Glycogenesis Definition: synthesis of glycogen from glucose. Site: cytosol of liver & muscles. Steps:
  • 23. Glycogenolysis Definition: breakdown of glycogen to glucose in liver or G6P in muscles ( due to absence of G6 phosphatase in muscles). Importance: In muscles: source of energy during exercise. In liver: source of blood glucose during 18 hours starvation. Steps:
  • 25. Von Gierke’s disease Genetic disease due to deficiency of G6 phosphatase Accumulation of glycogen in liver& kidney Hepatomegaly, renal failure & fasting hypoglycemia. G6P HMP PRPP Purine nucleotide Uric acid Hyperuricemia (Gout).