biochemistry of carbohydrates...3-pg 2-pg pep pyr 1. hexokinase 2. phosphoglucoisomerase 3. pfk1 4....
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Biochemistry of Carbohydrates
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Biochemistry of Carbohydrates
Glycolysis • The Breakdown of Glucose
• Primary Energy Source of Cells
• Central Metabolic Pathway
• All Reactions Occur in Cytoplasm
• Two Phases
• Produces 2 Pyruvates, 2 ATP, 2 NADH
• Regulation
Phase 1
ATP Investment
ATP ADP
ATP ADP
Phase 2
Energy Production
2 ADP 2 ATP
2 ADP 2 ATP
2 NAD+ 2 NADH
Glycolysis • Glucose
• Stored in Polymers (Amylose/Amylopectin/Glycogen)
• poison
• Readily Released
• Travels Easily in Blood
• Made from Simple Precursors (Gluconeogenesis)
Glycolysis • Phase 1
Glucose Glucose-6-Phosphate (G6P)
Hexokinase
• Regulated Step of Glycolysis
• ΔG°’ = -16.7 kJ/mol
+ H+
Glycolysis • Hexokinase
Hexokinase
ATP
Glucose
• Found in Virtually All Cells
• Not Specific to Glucose
• Glucokinase - Higher Km
• Inhibited by G6P Product
Glycolysis • Phase 1
Glucose-6-Phosphate (G6P( Fructose-6-Phosphate (F6P(
Phosphoglucoisomerase
)G6P Isomerase(
Readily Reversible Reaction ΔG°’ = + 1.7 kJ/mol
Glycolysis • Phase 1
Fructose-6-Phosphate (F6P( Fructose-1,6-Bisphosphate (F1,6BP(
Phosphofructokinase
• Important Regulatory Enzyme of Glycolysis
• ΔG°’ = -14.2 kJ/mol
(PFK-1)
+ H+
Glycolysis • Phosphofructokinase
• AMP and Fructose 2,6 Bisphosphate Activate
• ATP Inhibits
• Two Binding Sites for ATP
Glycolysis • Phase I
Fructose 1,6 Bisphosphate (F1,6 BP(
Aldolase
Glyceraldehyde-3-Phosphate
)GA3P(
Dihydroxyacetone
Phosphate (DHAP
• ΔG°’ = +23.9 kJ/mol
Glycolysis • Aldolase Reaction
• Energy Barrier
• “Pushing”
• “Pulling”
F1,6BP <=> GA3P + DHAP
ΔG = 23.9 + RTln [GA3P][DHAP]
[F1,6BP] { }
ΔG = 23.9 + RTln [GA3P][DHAP]
[F1,6BP] { } ΔG = 23.9 + RTln [GA3P][DHAP]
[F1,6BP] { }
Glycolysis • Phase 2
• Readily Reversible Reaction
• ΔG°’ = 7.6 kJ/mol
• Diffusion-limited Enzyme
• Perfect Enzyme
Dihydroxyacetone Phosphate (DHAP(
Glyceraldehyde-3-Phosphate (GA3P(
Triose Phosphate Isomerase
Glycolysis • Phase 2
Glycolysis • Phase 2
• Only Oxidation of Glycolysis
• ΔG°’ = 6.3 kJ/mol
Glyceraldehyde-3-Phosphate (GA3P) 1,3 Bisphosphoglycerate (1,3 BPG)
Glyceraldehyde-3-Phosphate
Dehydrogenase (GA3PDH) Aldehyde Ester
Glycolysis • Phase 2
• Substrate Level Phosphorylation
• ΔG°’ = -18.9 kJ/mol
1,3 Bisphosphoglycerate (1,3 BPG(
3 Phosphoglycerate (3-PG(
Phosphoglycerate
Kinase
Three means of making ATP
1.Substrate level phosphorylation - high energy molecule adds phosphate to ADP
2. Oxidative phosphorylation - oxidative energy (electron movement) used in mitochondria to generate ATP
3. Photophosphorylation - light energy captured in chloroplasts of plants to make ATP
Glycolysis
Glycolysis • Phase 2
• Minor Source of 2,3 BPG
• ΔG°’ = 4.4 kJ/mol
3 Phosphoglycerate (3-PG(
Phosphoglycerate Mutase
2 Phosphoglycerate (2-PG(
Glycolysis • 2,3 BPG and Glycolysis
• 2,3 BPG Binds to Hemoglobin and Favors O2 Release
2,3 BPG
3-PG 2-PG
2,3 BPG
Phosphoglycerate Kinase Phosphoglycerate Mutase
1,3 BPG
Released Freely in Erythrocytes
and Placental Cells
Released at a Low Level in All Cells
Pi Pi Pi
ADP ATP
Glycolysis • Phase 2
• ΔG°’ = 1.8 kJ/mol
Enolase
2 Phosphoglycerate (2-PG( Phosphoenolpyruvate (PEP(
Glycolysis • Phase 2
• Substrate Level Phosphorylation
• ΔG°’ = -31.7 kJ/mol
• Heat releases
• Essentially Irreversible
Pyruvate Kinase
Phosphoenolpyruvate (PEP( Pyruvate (Pyr(
Glycolysis • Pyruvate Kinase
• Third Regulated Enzyme of Glycolysis
• Inhibited by ATP, Alanine
• Activated by F1,6BP
• Inactivated by Phosphorylation
• Regulation Important for Gluconeogenesis
Glycolysis • Pyruvate Kinase
Glycolysis • Summary
Glucose + 2 ADP + 2Pi + 2 NAD+
Yields
2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
Glycolysis • Fermentation in Yeast/Bacteria
Glucose
GA3P
NADH + H+
NAD+
1,3 BPG
Pyruvate
(PYR)
O2 Helps to
Make NAD+
In Absence of Oxygen
Product of Process
X
Glycolysis • Fermentation in Yeast/Bacteria
Glycolysis • Fermentation in Animals
Glucose
GA3P
NADH + H+
NAD+
1,3 BPG
Pyruvate
(PYR)
Product of Process
X O2 Helps to
Make NAD+
Glycolysis • Fermentation in Animals
Glycolysis • Fates of Pyruvate
• Pyruvate Not an End
Point
• Important for Amino
Acids,Energy,
Fermentation
Glycolysis • Metabolism of Other Sugars - Galactose
Glycolysis • Metabolism of Other Sugars - Galactose
Lactose
Lactase
Galactose Glucose
Reduced Quantities in Adults Leads to Lactose Intolerance
Glycolysis • Metabolism of Other Sugars - Fructose
Fructose Fructose-1-Phosphate
(F1P)
Fructokinase
F1P DHAP + Glyceraldehyde
Glyceraldehyde-3-Phosphate
Fructoaldolase
To Glycolysis
Glycolysis • Metabolism of Other Sugars - Fructose
Fructose
F1P
DHAP + GA3P
Regulatory Enzyme Bypassed
Regulatory Enzyme Bypassed
Excess Pyruvate?
Gluconeogenesis • Synthesis of Glucose
• Important for Regulating Blood Glucose
• Reactions in Cytoplasm, Mitochondrion, Endoplasmic Reticulum
• In the Body - Liver and Kidney
Gluconeogenesis • Synthesis of Glucose
• Four Reactions in Gluconeogenesis Replace Three
Reactions in Glycolysis
• All Other Reactions are Simply the Reverse of
Glycolysis Reactions
• Two Pyruvates Needed for Each Glucose
Gluconeogenesis • Synthesis of Glucose (Hexokinase)
)PFK)
G6Pase
F1,6BPase
(Pyruvate Kinase)
PEPCK
Pyruvate Carboxylase
Gluconeogenesis • Reactions of Gluconeogenesis
Glucose
G6P
F6P
F1,6BP
DHAP + G3P
GA3P
1,3 BPG
3-PG
2-PG
PEP
Pyr
1. Hexokinase
2. Phosphoglucoisomerase
3. PFK1
4. Aldolase
5. Triose Phosphate Isomerase
6. GA3PDH
7. Phosphoglycerate Kinase
8. Phosphoglycerate Mutase
9. Enolase
10. Pyruvate Kinase
11. Glucose-6-Phosphatase
10. Phosphoglucoisomerase
9. F1,6 Bisphosphatase
8. Aldolase
7. Triose Phosphate Isomerase
6.. GA3PDH
5. Phosphoglycerate Kinase
4. Phosphoglycerate Mutase
3.. Enolase
2.. PEPCK
1. Pyruvate Carboxylase
Run as Reverse of
Glycolysis Reactions
Gluconeogenesis • Reactions of Gluconeogenesis
• Reaction #1
• Step 1 of Bypassing Pyruvate Kinase
• Occurs in Mitochondrion
Gluconeogenesis • Reactions of Gluconeogenesis
Pyruvate
)Pyr( Oxaloacetate
)OAA(
Pyruvate Carboxylase
• Reaction #1
• Step 1 of Bypassing Pyruvate Kinase
• Occurs in Mitochondrion
Gluconeogenesis • Reactions of Gluconeogenesis
Biotin Carrying CO2
CO2
Gluconeogenesis • Reactions of Gluconeogenesis
• Reaction #2
• Occurs in cytoplasm
• Second Triphosphate Necessary
Phosphoenolpyruvate Carboxykinase
(PEPCK)
Oxaloacetate
) OAA( Phosphoenolpyruvate
(PEP(
Gluconeogenesis • Reactions of Gluconeogenesis
Fructose 1,6 Bisphosphatase
) FBPase(
Fructose 1,6 Bisphosphate
)F1,6BP(
Fructose 6 Phosphate
)F6P(
Glycolysis Enzyme Required ATP
• Reaction # 9 of Gluconeogenesis
• Not the Reversal of the PFK Reaction
• Energy Realized by Not Regenerating ATP
Gluconeogenesis • Reactions of Gluconeogenesis
• Reaction # 11 of Gluconeogenesis
• Not the Reversal of the Hexokinase Reaction
• Energy Reserved by Not Regenerating ATP
• Occurs in Endoplasmic Reticulum
Glucose 6 Phosphate
)G6P( Glucose
Glucose-6-Phosphatase
(G6Pase)
Glycolysis Enzyme Required ATP
Gluconeogenesis and Glycolysis • Regulation
Glycolysis
Glucose + 2 ADP + 2Pi + 2 NAD+
Yields
2 Pyruvate + 2ATP + 2 NADH + 2 H+ + 2 H2O
Gluconeogenesis
2 Pyruvate + 2 NADH + 4 ATP + 2 GTP
Yields
Glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi
Gluconeogenesis Requires More Energy Than Glycolysis Generates
Futile Cycle Results if Both Running Simultaneously
ATP/GTP Burned, Nothing but Heat Produced
Gluconeogenesis and Glycolysis • Regulation
Gluconeogenesis and Glycolysis • Regulation
Glycolysis
Gluconeogenesis
Gluconeogenesis and Glycolysis • Regulation
Glycolysis
Hexokinase - G6P (-)
PFK - AMP (+), ATP (-), F2,6BP (++)
Pyruvate Kinase - Alanine (-), ATP (-), F1,6BP (+)
Gluconeogenesis
FBPase - Citrate (+), AMP (-), F2,6BP (- -)
PEPCK - ADP (-)
Pyruvate Carboxylase - ADP (-), Acetyl-CoA (+)
Reciprocal Regulation
Low Energy
High Energy
Other
F2,6BP is Made Upon Insulin Stimulation - Favors Glycolysis
F2,6BP is Broken Down Upon Glucagon Stimulation - Favors Gluconeogenesis
Gluconeogenesis and Glycolysis • Regulation
Cori Cycle
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