biochemistry of carbohydrates...3-pg 2-pg pep pyr 1. hexokinase 2. phosphoglucoisomerase 3. pfk1 4....

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


Glucose-6-Phosphate (G6P( Fructose-6-Phosphate (F6P(

Phosphoglucoisomerase

)G6P Isomerase(

Readily Reversible Reaction ΔG°’ = + 1.7 kJ/mol


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] { }


• Readily Reversible Reaction

• ΔG°’ = 7.6 kJ/mol

• Diffusion-limited Enzyme

• Perfect Enzyme

Dihydroxyacetone Phosphate (DHAP(

Glyceraldehyde-3-Phosphate (GA3P(

Triose Phosphate Isomerase


• Only Oxidation of Glycolysis

• ΔG°’ = 6.3 kJ/mol

Glyceraldehyde-3-Phosphate (GA3P) 1,3 Bisphosphoglycerate (1,3 BPG)


Dehydrogenase (GA3PDH) Aldehyde Ester


• 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


• Minor Source of 2,3 BPG

• ΔG°’ = 4.4 kJ/mol


Phosphoglycerate Mutase


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


• ΔG°’ = 1.8 kJ/mol

Enolase

2 Phosphoglycerate (2-PG( Phosphoenolpyruvate (PEP(


• 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


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


• Reaction #1

• Step 1 of Bypassing Pyruvate Kinase

• Occurs in Mitochondrion


Pyruvate

)Pyr( Oxaloacetate

)OAA(

Pyruvate Carboxylase

• Reaction #1

• Step 1 of Bypassing Pyruvate Kinase

• Occurs in Mitochondrion


Biotin Carrying CO2

CO2


• Reaction #2

• Occurs in cytoplasm

• Second Triphosphate Necessary

Phosphoenolpyruvate Carboxykinase

(PEPCK)

Oxaloacetate

) OAA( Phosphoenolpyruvate

(PEP(


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


• 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


Glycolysis

Gluconeogenesis


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

Cori Cycle

biochemistry of carbohydrates...3-pg 2-pg pep pyr 1. hexokinase 2. phosphoglucoisomerase 3. pfk1 4....

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