Glycolysis
Overview
Outline - Chapter 8 in Text
Overview
Differences between cells
Glycolysis: Glucose
Pyruvate
Gluconeogenesis: Pyruvate
Glucose
(glucose)
CH O
(pyruvate)
2C H O
Embden-Meyerhof pathway
Oxidation reaction
Occurs in all human cells
Requires 10 steps (3 stages)
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Glucose Metabolism Overview
Glucose metabolized differently in different cells
Red blood cells: No mitochondria
Glucose Metabolism (cont.)
Muscle:
lactate
Glycogen, Krebs, lactate, or pentose phosphates
Liver:
Brain:
Glycogen, Krebs, TAG, lactate, or pentose
phosphates
Krebs or pentose phosphates
Adipose Tissue:
TAG (Primarily)
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Stages of Glycolysis
Features to Look For
Priming Stage:
Glucose
fructose 1,6-bisphosphate
Splitting stage:
fructose 1,6-bisphosphate
2 glyceraldehyde-3-phosphate
Oxidative-phosphorylation stage:
2 glyceraldehyde-3-phosphate
2 pyruvate
Don’t get lost in details.
Stages
Additional reactants/products
ATP: Goal is to produce energy
NADH/NAD : This is redox
Reversibility - Usually a control point
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Step 1
Step 2
glucose + ATP
glucose-6-phosphate
fructose-6-phosphate
glucose-6-phosphate + ADP
Catalyst: Hexokinase
Reaction Type: Phosphorylation
Irreversible
Catalyst: phosphoglucose isomerase
Reaction Type: Isomerization
Reversible
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Step 3
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Summary: Priming Stage
glucose + ATP
glucose-6-phosphate + ADP
glucose-6-phosphate
fructose-6-phosphate
fructose-6-P + ATP
fructose-1,6-bisP + ADP
fructose-6-phosphate + ATP
fructose-1,6-bisphosphate + ADP
Net:
glucose + 2 ATP
Catalyst: 6-phosphofructo-1-kinase
Reaction Type: Phosphorylation
Irreversible
fructose-1,6-bisphosphate + 2 ADP
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Step 4
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Step 5
+
fructose-1,6-bisphosphate
glyceraldehyde-3-phosphate
+ dihydroxyacetone phosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
Catalyst: fructose-bisphosphate aldolase
Reaction Type: Cleavage
Reversible
Catalyst: Triose phosphate isomerase
Reaction Type: Isomerization
Reversible
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Summary: Splitting Stage
fructose-1,6-bisphosphate
Step 6
glyceraldehyde-3-phosphate
+ dihydroxyacetone phosphate
dihydroxyacetone phosphate
glyceraldehyde-3-phosphate
glyceraldehyde-3-phosphate + NAD
Net:
+ P
fructose-1,6-bisphosphate
1,3-bisphosphoglycerate + NADH + H
2 glyceraldehyde-3-phosphate
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Oxidative Phosphorylation
Catalyst: glyceraldehyde-3-phosphate
dehydrogenase
Reaction Type: Oxidative Phosphorylation
Reversible
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Step 7
Phosphorylation
Oxidative Phosphorylation
1,3-bisphosphoglycerate + ADP
3-phosphoglycerate + ATP
Catalyst: phosphoglycerate kinase
Reaction Type: Phosphorylation
Reversible
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Step 8
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Step 9
2-phosphoglycerate
Catalyst: phosphoglyceromutase
Reaction Type: Isomerization
Reversible
2-phosphoglycerate
3-phosphoglycerate
phosphoenolpyruvate + H O
Catalyst: enolase
Reaction Type: Elimination or Dehydration
Reversible
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Step 10
Summary: Ox. Phos. Stage
glyceraldehyde-3-P
+ NAD + P
1,3-bisPglycerate + ADP
3-phosphoglycerate
2-phosphoglycerate
1,3-bisPglycerate
+ NADH + H
3-Pglycerate + ATP
2-phosphoglycerate
phosphoenolpyruvate
phosphoenolpyruvate + ADP
phosphoenolpyruvate + ADP
pyruvate + ATP
pyruvate + ATP
Catalyst: pyruvate kinase
Reaction Type: Phosphorylation
Irreversible
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Net:
glyceraldehyde-3-P + NAD
pyruvate + NADH + H
+ 2 ADP + P
+ 2 ATP
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Note: All reactions need to be multiplied by two (2)
Summary: Glycolysis
Fate of Pyruvate
glucose + 2 NAD
2 pyruvate + 2 NADH
fructose-1,6-bisP + 2 ADP
2 glyceraldehyde-3-P
2 pyruvate
+ 2 NADH + 2 H
+ 4 ATP
Priming:
glucose + 2 ATP
Splitting:
fructose-1,6-bisP
Ox. Phos.:
2 glyceraldehyde-3-P
+ 2 NAD
+ 4 ADP + 2 P
Gluconeogenesis:
pyruvate
glucose
Anaerobic glycolysis:
pyruvate
lactate
Fermentation:
pyruvate
ethanol + CO
Net:
Carbon:
glucose
ATP:
2 ADP + 2 P
Redox:
2 NAD
2 pyruvate
2 ATP
2 NADH + 2 H
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Anaerobic Glycolysis
Regulation
(See Table 81, p. 200)
The following steps are irreversible:
#1: glucose
glucose-6-phosphate
inhibited by: glucose-6-phosphate
#3: fructose-6-P
fructose-1,6-bisP
inhibited by: fructose-1,6-bisP, ATP, citrate
activated by: AMP, fructose-2,6-bisP
#10: PEP
pyruvate
inhibited by ATP and acetyl-CoA
pyruvate + NADH
lactate + NAD
Reaction ’regenerates’ NAD required for
glycolysis
Occurs in cytosol
Net reaction:
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Fructose Phosphates
Fructose-6-phosphate is a glycolysis intermediate.
Glucose-6-phosphate
isomerase
PFK-2 (High glucose)
Fructose-6-phosphate
Fructose-2,6-bisP
Activates PFK-1
PFK-1
Fructose-1,6-bisphosphate
PFK-1
ATP, citrate
AMP
Inhibited
Activated
Pyruvate Kinase
Last step in Glycolysis
Enzyme activated by:
AMP: Energy supply in cell is low
Fructose-1,6-bisP: glucose conc. in cell is
high
Enzyme inhibited by:
ATP: Energy supply in cell is high
Acetyl-CoA: pyruvate isn’t needed
fructose-2,6-bisP fructose-1,6-bisP
fructose-bisphophatase
citrate
AMP
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fructose-2,6-bisP
Gluconeogenesis
Synthesis of PEP
(Textbook section 8.4, pp 201-205)
pyruvate + CO + H O + ATP
oxaloacetate + ADP + P + H
Synthesis of glucose from non-carbohydrate
precursors
lactate, pyruvate, glycerol, amino acid
derivatives
Occurs primarily in liver
7 reversible steps of glycolysis used.
3 ’By-pass’ steps required
First step is hardest and most costly.
Catalyst: pyruvate carboxylase (biotin coenzyme)
Reaction Type: Carboxylation
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Fructose-6-Phosphate
OA to PEP
fructose-1,6-bisphosphate + H O
oxaloacetate + GTP
phosphoenolpyruvate + GDP + CO
Catalyst: PEP carboxykinase
Reaction Type: phosphorylation/decarboxylation
Occurs in cytosol or mitochondria (depending on
type of cell in humans)
Carrier required to transport OA
fructose-6-phosphate + P
Catalyst: fructose-1,6-bisphosphatase
Reaction Type: Phosphorylation (hydrolysis)
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Formation of Glucose
Futile Cycles
Results in large loss of energy
Avoided by proper activation/inhibition of
regulatory enzymes
Ex.
glucose-6-phosphate + H O
glucose + P
Net:
ATP + H O
Catalyst: glucose-6-phosphatase
Enzyme only present in liver and kidney
Reaction Type: Phosphorylation (hydrolysis)
ADP + P
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Gluconeogenesis Precursors
Glycerol
(Textbook section 8.4, pp 206-208)
Pyruvate: From glycolysis
Lactate: Anaerobic glycolysis
Glycerol: From triglycerides
-ketones: From amino acids
glycerol + ATP
glycerol-3-P + ADP
glycerol-3-phosphate + NAD
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dihydroxyacetone phosphate + NADH + H
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Cori Cycle
Amino Acids
Muscle:
Pyruvate
Lactate (+2 ATP)
Glucose
Anaerobic: occurs during exercise
Liver:
Pyruvate
Glucose (-6 ATP)
Occurs during rest/recovery
Lactate
pyruvate + glutamate
alanine +
-ketoglutarate
Transamination reaction
Cycle ’costs’ 4 equivalents of ATP
’Paid’ during times of high ATP
Generates important fuel
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Glucose-Alanine Cycle
Muscle:
Amino acids
Glutamate + Pyruvate
glutamate
Metabolism of Fructose
(Textbook section 8.5, pp 209-212)
Fructose + ATP
Fructose-1-P
DHAP + glyceraldehyde
glyceraldehyde + ATP
Liver:
-ketoglutarate + alanine
Pyruvate
Glutamate + Pyruvate
Glucose
NH
Glutamate
Fructose-1-P + ADP
-ketoglutarate + alanine
Occurs during exercise
urea
glycerald.-3-P + ADP
Occurs primarily in liver
Bypasses two regulatory steps
Cleavage reaction much slower than 1
phosphorylation
Occurs during rest/recovery
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Cycle removes toxic NH from body
Metabolism of Galactose
Galactose + ATP
Galactose-1-P + ADP
Galactose-1-P + UDPG
UDP-Galactose + Glucose-1-P
UDP-Galactose
UDP-Glucose
Galactose from milk
Metabolism in infants (as shown) differs from
adults
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