Introduction of Glucose Metabolism Lecture-4

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Introduction of Glucose Metabolism Lecture-4
GLUCONEOGENESIS 
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GLUCONEOGENESIS 

• Gluconeogenesis is the synthesis of glucose from
  glucogenic precursors
• which are not of carbohydrate origin
  (gluconeogenic precursors)
•  
• It occurs during prolonged fasting to synthesize
  glucose for tissues
• requiring continuous supply of glucose as a
  source of energy
• Brain, RBCs, Kidney medulla, Lens, Cornea,
  Testes, sk.ms
• Gluconeogenesis occurs ONLY in the liver
  kidneys

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Gluconeogenesis An Overview

• Both mitochondria and Cytosol
• Exception Glycerol, only cytosol
• Gluconeogenic substrates
• Glycerol
• Lactate and Pyruvate
• Glucogenic amino acids

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Gluconeogenesis Pathway
Dephosphorylation of G-6-P
Dephosphorylation of F 1,6-P
Transport of OAA
Carboxylation of pyruvate
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Gluconeogenic precursors

• 1- Intermediates of glycolysis
• by reverse of steps of glycolysis (except 4
  steps that need 4 different enzymes)
• 2- Intermediates of citric acid cycle
• are converted to oxalacetate then to
  glucose
• 3- Lactate
• Lactic acid formed of anaerobic glycolysis
  in cells as RBCs skeletal muscles
• are transported in blood to liver to be
  converted to pyruvate then to glucose (Cori
  cycle)
• 4- Glycerol
• Glycerol is derived from the lipid
  triacylglycerol in adipose tissue.
• Glycerol is converted into
  dihydroxyacetone phosphate (intermediate of
• glycolysis) then to glucose.
• 5- Glucogenic amino acids of proteins
• Glucogenic amino acids are deaminated to
  form a-ketoacids
• a-keto acids are converted to pyruvate or
  intermediates of citric acid cycle then to
  glucose

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GLUCOSE
Triacylglycerol in adipose tissue
Precursors of Gluconeogenesis
Fatty acids
Gluconeogenesis
Glycerol
Lactate
Pyruvate
Oxalacetate
Intermediate of CITRIC ACID CYCLE
Glucogenic amino acids in proteins as sk. ms.
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Glycerol as agluconeogenic Substrate
Glycerol Kinase
Glycerol
Glycerol 3-phosphate
ATP
ADP
NAD
Glycerol 3-phosphate dehydrogenase
NADH
Dihydroxyacetone phosphate
Glucose
GK Glycerol kinase only in liver kidneys
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Glucogenic Amino Acids
Glycine, Alanine
Amino acids
Pyruvate
Aspartate Aspargine
Glutamate Glutamine
Amino acids
Phenylalanine Tyrosine
Methionine Valine
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Cori Cycle
Lactate is a gluconeogenic precursor
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Gluconeogenesis Pathway
Dephosphorylation of G-6-P
Dephosphorylation of F 1,6-P
Transport of OAA
Carboxylation of pyruvate
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Pruvate Carboxylase and PEP-CK
Pyruvate carboxylase PEP-CK Pyruvate kinase
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Fructose 1,6-Bisphosphatase
Fructose 1,6-bisphosphatase PFK-1
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Glucose 6-Phosphatase
Glucose 6-phosphatase Glucokinase
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GluconeogensisE- Consumed
Six High-Energy Phosphate Bonds From Pyruvate
to Glucose
2 ADP
2 ATP
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Gluconeogenesis Regulation

• Reciprocal control
• Gluconeogenesis Glycolysis
• Allosteric
• Acetyl CoA (Pyruvate carboxylase)
• Glucagon (I/G ratio)
• Induction (PEP-CK)

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Unique enzymes of gluconeogenesis
Reactions 1, 2, 3 4 are catalyzed by enzymes
NOT used in glycolysis
GLUCOSE
1- Pyruvate to oxalacatate by pyruvate
carboxylase 2- oxalacetate to phosphoenol
pyruvate by PEP carboxykinase 3- Fructose
1,6 bisphosphate to fructose 6 phosphate by
fructose 1,6 bisphosphatase 4- Glucose
6-phosphate to glucose by glucose
6-phosphatase
GLUCONEOGENESIS
Other reactions of gluconeogenesis are catalyzed
by same enzymes of glycolysis in the reverse
direction