BIOC 460 DR' TISCHLER

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BIOC 460 - DR. TISCHLER LECTURE 21
GLYCOLYSIS AND GLUCONEOGENESIS-1
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OBJECTIVES

• Glycolysis reactions
• a) in which ATP is used
• b) that produce ATP for cell energy
• c) that requires NAD high energy phosphate
  intermediate produced
• 2. Why NAD must be regenerated for glycolysis
  how accomplished under anaerobic conditions.
• 3. Metabolic role of niacin
• 4. Characteristics of the H4 (LDH1) and M4
  (LDH5) isozymes

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PHYSIOLOGICAL PREMISE What biochemical
properties in the liver allow us to handle a
large dietary intake of glucose without becoming
severely hyperglycemic? First, to ensure that
glucose can readily enter the liver, its
transport is independent of any metabolic
controls. Second, as soon as glucose enters the
liver it is quickly phosphorylated by a kinase
enzyme that has a high capacity for handling the
glucose. Why is immediate phosphorylation of
glucose important? Recall that phosphate contains
several negative charges. Since membranes are
hydrophobic, they do not readily permit
penetration of molecules bearing charges unless
there is a specific transport protein to permit
their movement across the membrane. Hence it is
these conditions in the liver that contribute to
the rapid removal of glucose as it passes the
liver immediately after entering the circulation
from intestinal cells.
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HEXOKINASE/GLUCOKINASE FEATURES
Glucose-6-phosphate ADP
Glucose ATP
P
P
P
P
P
P
PO32-
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FEATURES OF PFK-1 REACTION
Fructose-1,6-bisP ADP
Fructose-6-P ATP
P
P
P
P
P
P
PO32-
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PHASE 2 OF GLYCOLYSIS

• fructose-1,6-bisphosphate is split

• 2 molecules of glyceraldehyde-3-P provided for
  second half of glycolysis

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Glyceraldehyde-3-P (from first half of
glycolysis)
NAD Pi
Glyceraldehyde-3-P dehydrogenase
NADH H
3-Pglycerate
1,3-BisPglycerate
Pglycerate kinase
Phosphoglycerol mutase
ATP
ADP
Enolase
Phosphoenolpyruvate
2-Pglycerate
ADP
Pyruvate kinase
ATP
Pyruvate
Figure 1B. The reduction-oxidation and ATP
formation phase (phase 3)
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GLYCERALDEHYDE-3-P DEHYDROGENASE FEATURES
Glyceraldehyde-3-P NAD Pi ?
1,3-BisPglycerate NADH
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PHOSPHOGLYCERATE KINASE FEATURES
1,3-bisphosphoglycerate ADP ?
3-phosphoglycerate ATP
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PYRUVATE KINASE FEATURES
Phosphoenolpyruvate ADP ? Pyruvate ATP

• high-energy intermediate drives the reaction

• negative ?Go makes this step very favorable

• second site of ATP production (substrate-level
  phosphorylation)
• two ATP from two triose molecules in second half

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LACTATE DEHYDROGENASE
pyruvate NADH H ? lactate NAD
(anaerobic glycolysis)
tetramer of H and/or M subunits H4 (LDH1) to M4
(LDH5) M4 principal form in anaerobic
skeletal muscles, red blood cells produces
lactate key form linked to anaerobic glycolysis
functions best when cytoplasmic pyruvate
is high H4 and H3M1 principal forms in
heart, aerobic skeletal muscles high
affinity for lactate (lower Km)
allosterically inhibited by pyruvate
favors oxidation of lactate to pyruvate
prevents conversion of pyruvate to lactate
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Glyceraldehyde-3-P
Anaerobic regeneration of NAD
Glyceraldehyde-3-P dehydrogenase
3-Pglycerate
1,3-BisPglycerate
Phosphoglycerol mutase
Pglycerate kinase
ATP
ADP
Enolase
Phosphoenolpyruvate
2-Pglycerate
ADP
Pyruvate kinase
ATP
Pyruvate
Lactate
Lactate dehydrogenase
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Glyceraldehyde-3-P
Anaerobic regeneration of NAD
Glyceraldehyde-3-P dehydrogenase
NAD
NAD
NADH H
NADH H
NAD
3-Pglycerate
1,3-BisPglycerate
NADH H
Pglycerate kinase
Phosphoglycerol mutase
NAD
NAD
ATP
ADP
NADH H
NADH H
Enolase
NAD
NADH H
Phosphoenolpyruvate
2-Pglycerate
NADH H
ADP
NAD
NAD
NADH H
NADH H
Pyruvate kinase
NADH H
NADH H
ATP
NAD
Pyruvate
Lactate
Lactate dehydrogenase
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Glyceraldehyde-3-P
Anaerobic regeneration of NAD
NAD
Pi
Glyceraldehyde-3-P dehydrogenase
NADH H
3-Pglycerate
1,3-BisPglycerate
Phosphoglycerol mutase
Pglycerate kinase
ATP
ADP
Enolase
Phosphoenolpyruvate
2-Pglycerate
ADP
Pyruvate kinase
NADH H
ATP
NAD
Pyruvate
Lactate
Lactate dehydrogenase
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Fructokinase
FRUCTOSE-1-P
FRUCTOSE
ATP
ADP
Figure 2. The pathway for fructose metabolism in
liver
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Figure 3. Principal liver pathway for metabolism
of galactose