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IntroductoryBiochemistry
Glucose Metabolism
Glucose and Glycolysis
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Glucose occupies a centralposition in the metabolism of
most cells.
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The Pathways of GlucoseMetabolism
GLUCOSE
GLYCOGEN
PYRUVATE
GLYCOLYSIS GLUCONEOGENESIS
glycogen
synthesis
glycogenolysis
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You will be given this
scheme on your finalexam
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The Structures of Glucose
Glucose is a six-carboncompound with one
aldehyde groupand fivehydroxyl groups..
which cyclizes to form
a 6-membered ring.
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Glycolysis
Occurs in the cytosol.
Serves as the first step in the complete oxidation of
glucose to CO2 and H2O.
Production of a small amount of ATP.
Provides building blocks for the synthesis of cellular
molecules.
Can occur under aerobic OR anaerobic conditions.
Typically occurs under aerobic conditions
Can only metabolize fat aerobically
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Glycolysis
2x
EnergyPayoutTriose phase
energyInvestmentHexose phase
2x
2x
2x
2x
2
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Phosphorylation reactions
+ H+
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The Reaction Catalyzed by
Hexokinase:first ATP investment
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Glucose and Fructose areStructural Isomers
aldehyde ketone
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The Reaction Catalyzed by
PFK-1: second ATP investment
+ H+
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Glucose G6P F6P F-1,6-BP
Glycogen
HK Isomerase PFK-1
Committed
step
The reaction catalyzed by PFK-1 isthe committed step in glycolysis
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The Lysis in Glycolysis
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The Production of Two Moleculesof Glyceraldehyde 3-Phosphate
Via two separate reactions(lysisand isomerization), two molecules
of GAP are produced from onemolecule of fructose-1,6-
biphosphate.
Lysis
Isomerization
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One Molecule of GlucoseProduces Two Molecules
of GAP
C6
C6
C6
C6
C3 C3
C3
C3
C3
C3
C3
C3
C3
C3
C3
C3
C3
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The Oxidation Reactionin Glycolysis
1,3-BPG is a high-energy intermediate
R group
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1,3-BPG has a large phosphoryl-transfer potential
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Synthesis of ATP
This is a phosphoryl-transfer reaction and,
specifically, a substrate-levelphosphorylation (SLP) reaction.
Paying back the debt
This reaction happens twicefor every glucose molecule
Coupled reaction
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An Isomerization
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The Generation of PEP a high-energy intermediate
This is adehydrationreaction.
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The Reaction Catalyzed by PyruvateKinase
In this reaction, large amounts offree energy are released during the
conversion of enolpyruvate topyruvate.
SLP reaction
+ H+ +
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Balanced Equation for Glycolysis
Glucose + 2ATP + 2NAD+ + 2Pi + 4ADP +2H+
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In glycolysis, the NET yield of ATPmolecules per molecule of glucose is 2.
NET YIELD =GROSS YIELDINPUT2 ATP = 4 ATP2 ATP
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The rate of glycolysis is tightlyregulated in all cells.Regulation is important to ensure that:
Cells energy needs met. Fuel is not wasted.
There are appropriate levels of
intermediates required for other purposes.
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The rate of flux through metabolicpathways is regulated by four major
processes:
Substrate availability.
Alteration of enzyme activity.
Alteration of amount of enzyme.
Compartmentation.
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Hexokinase is inhibited by its
product, G-6P
Glucose
Hexokinase
Glucose-6-phosphate
-
productinhibition
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PFK-1 is allosterically regulated byADP/AMP and PEP
The concentrations
of ADP/AMPin a cellis a good indicatorof the need for ATP.
Elevated PEP levels signal that theproducts of glycolysis are not being
consumed.
Glucose
Fructose-6-P
Fructose-1,6-BP
Phosphoenolpyruvate
Pyruvate
ATP
ADP/AMP+-
Feedback
Inhibition
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Pyruvatekinase
Pyruvate kinase is an allosteric enzyme:feedforward activation by F-1,6-BP
+
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PFK-1 and PKboth inhibited by
ATP
Most enzymes catalyzereversible reactions
Synchronous regulation ofirreversible reactions
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Glycolysis is regulated bysignals outside the cell as well
as by signals inside the cell
by insulin by glucagon
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The Reactions of Glycolysis
1. glucose + ATP glucose-6-phosphate + ADP + H+ ATP Investment2. glucose-6-phosphate fructose-6-phosphate Isomerization3. F-6-P + ATP fructose-1,6-bisphosphate + ADP+ H+ ATP Investment4. F-1,6-BP GAP + DHAP Lysis5. DHAP GAP Isomerization6. GAP + NAD+ + Pi 1,3-BPG + NADH + H+ Oxidation7. 1,3-BPG + ADP 3-phosphoglycerate + ATP Substrate level phosphorylation (SLP)8. 3-phosphoglycerate 2-phosphoglycerate Isomerization9. 2-phosphoglycerate phosphoenolpyruvate + H2O Dehydration10. PEP + ADP + H+ pyruvate + ATP SLP