Fundamentals of Biochemistry 2/e

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Transcript Fundamentals of Biochemistry 2/e

Chapter 13
Chem 341
Suroviec Fall 2013
I. Overview
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Glycolysis converts to two C3 units. The free energy released in this process is harvested to synthesize
ATP from ADP and Pi
I. Overview
A.
Some pathways are irreversible
B.
Catabolic and anabolic pathways MUST
differ
C. Every metabolic pathway has a 1st committed step
II. Glucose
A. Glucose
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6 carbon sugar with aldehyde group
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 form: OH group of the anomeric C is on OPPOSITE side of ring from CH2OH
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 form: OH group of the anomeric C is on SAME side of ring from CH2OH
II. Glucose
C. Glycogenolysis
– Only liver can make glucose available to the liver at large
III. Glycolysis
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Stage I. Energy investment
– Glucose is phosphorylated and cleaved
– Uses 2 ATP
Stage II. Energy recovery
– 2 molecules of glyceraldehyde-3phosphate converted to pyruvate
– Produces 4 ATP
IV. Reactions of Glycolysis
A.
Hexokinase
Metabolically irreversible reaction
B. Phosphoglucose Isomerase
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Conversion of G6P to F6P
C. Phosphofrutokinase
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PFK phosphorylates FBP
Operates similar to hexokinase
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Tetrameric enzyme
R and T states in equilibrium
ATP is both a substrate and and allosteric
inhibitor
C. PFK
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Each PFK has 2 binding site
– Substrate site
– Inhibitor site
Inhibitor site binds ATP only in T state
Shifts equilibrium in favor of T at high
ATP concentrations
D. Aldolase
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Catalyzes cleavage of FBP to form GAP and
DHAP
E. Triose Phosphate Isomerase
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GAP continues down the glycolytic pathway
DHAP and GAP are ketose-aldose isomers
Final reaction Stage I
F. Glyceraldehyde-3-Phosphate Dehydrogenase
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Exergonic reaction
Synthesis of high energy 1,3-BPG
G. Phosphoglycerate Kinase
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Bilobal with Mg2+
1,3-BPG common intermediate whose consumption pulls reaction
forward
H. Phosphoglycerate Mutase
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3PG is converted to 2PG
Phosphorylated His is needed to complete reaction
2,3-BPG allosteric inhibitor of deoxyhemoglobin
I. Enolase
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2PG dehydrated to PEP
Needs Mg2+
F- inhibitor of reaction
J. Pyruvate Kinase
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PEP is cleaved via PK to form
pyruvate
Forms ATP
Step 1: ADP nucleophilically attacks
the PEP, forms ATP
Step 2: Enolpyruvate tautomerizes
to pyruvate
3 products of glycolysis
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ATP
– Investment of 2 ATP per glucose
– Generation of 4 ATP
NADH
– Glucose oxidized
– 2 NAD+ reduced to NADH
– Electron transport
Pyruvate
– 2 molecules are produced
– Complete oxidation to CO2 done in
citric acid cycle
III. Fermentation
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Pyruvate
– Aerobic conditions
• completely oxidized to CO2 and H2O
– Anaerobic conditions
• converted to reduced end product to reoxidize NADH
A. Homolactic Fermentation
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Demand for ATP high
Supply of oxygen is low
B. Alcoholic Fermentation
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Forms CO2, ethanol and NAD+
TPP is essential cofactor of pyruvate
decarboxylase
IV. Control of Glycolysis
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Glycolysis operates continuously in most tissues
Flux must vary to meet needs
How do we determine to flux control
mechanisms?
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One 3 reactions of glycolysis potentially control
it:
– Hexokinase
– Phosphofrucokinase
– Pyrivate kinase