Glycolysis I

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Glycolysis I

• Ancient Metabolism
• Integrated
• Into Modern Biosystems

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Main Features

• Oldest of Pathways
• Occurs in Soluble Phase of Cytoplasm (Cytosol)
• Anaerobic Phase of Energy Metabolism
• Generates ATP
• Produces Pyruvate/Lactate
• Produces Many Important Intermediates

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Relationship to Other Pathways

• TCA Cycle
• Gluconeogenesis (in Liver and Kidney)
• Hexose Monophosphate Shunt (HMP)
• Metabolism of other Sugars, e.g., Fructose and
  Galactose
• Metabolism of Certain Amino Acids
• Lipid Metabolism
• Glycoprotein Synthesis

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Pay Attention to These

• Steps involving ATP
• Oxidative Step (NADH)
• Step involving Pi
• Regulated Steps
• Stoichiometry
• Tissue differences

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Glycolytic Functions

• Carbohydrates are converted to fat
• Glycogen is made
• Glycolysis provides intermediates to the hexose
  monophosphate shunt
• Glycolysis participates in the regulation of
  oxygen transport by hemoglobin
• Glycolysis and gluconeogenesis are involved with
  alcohol metabolism

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Typical Cell
Where are we going to be?
Peroxisome
Centriole
Mitochondrion
Rough ER
Smooth ER
Nucleus
Lysosome
Nucleolus
Plasma Membrane
Cytoskeleton
Golgi
Ribosomes
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Glycolysis Simplified(anaerobic)
Glucose
2ADP
2ATP
2NADH
4ATP 2 Net
4ADP
2Pyruvate
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The NAD ProblemNAD is required for glycolysis
NADH
NADH
NADH
NADH
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The NAD ProblemNADH accumulates, and NAD is
unavailable during anaerobiosis glycolysis stops
Glucose
Glucose
NADH
NADH
NADH
NADH
NO NAD
NADH
NADH
NADH
NADH
NADH
No Pyruvate
No ATP
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LDH to the Rescue
Lactate dehydrogenase catalyzes the oxidation of
NADH to NAD. Lactate accumulates under anaerobic
conditions..
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On Lactate Dehydrogenase(LDH)

• LDH has four subunits and five isozymes
• It can be used as a cardiac enzyme.
• Damaged or dying cells lyse, releasing their
  contents, e.g., LDH.
• Its blood levels slowly rise and peak
  approximately 24 hours after an MI (myocardial
  infarction).
• It can also be used to help diagnose liver
  disease.

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LDH Isozymes
Isozyme
Subunit composition

• I1
• I2
• I3
• I4
• I5

• HHHH
• HHHM
• HHMM
• HMMM
• MMMM

H Heart type M Muscle type
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Electrophoresis of LDH Isozymes
MMMM
MMMH
MMHH
MHHH
HHHH
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The many branches of glycolysis
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Blood
Glucose
Glycolipids Glycoproteins
Galactose
Ribose 5-P NADPH
Glycogen
Glucose 6-P
Glycerol 3-P
Fructose
Triose Phosphates
Ser
PEP
Gly
OAA
Ala
Pyruvate
Lactate
Acetyl CoA
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Details of Glycolysis
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First, we must get glucose into the cell.

• Glucose transport and glucose transporters

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END