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SURVEY OF BIOCHEMISTRY

Glycolysis

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Glycolysis Overview

• Glycolysis: breakdown of glucose into pyruvate with net production of ATP

• Occurs in cytosol

Glucose + 2 ADP + 2 NAD+ + 2 Pi

2 Pyruvate + 2 ATP + 2 NADH + 2 H+

10 steps

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Glycolysis: First 5 Steps

• Convert Glucose into G6P

• Convert G6P into F6P

• Convert F6P into FBP

• Split FBP into two molecules– GAP: ready for next step– DHAP: must convert into GAP before

proceeding

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Drawing Glucose

O

Draw the molecule glucose in the Haworth projection

• Start with the ring system

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4

5

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Drawing Glucose

Draw the molecule glucose in the Haworth projection

• Start with the ring system

• Add the substituents on the ring system

C1 - draw OH down C2 - draw OH down C3 - draw OH up C4 - draw OH down C5 - draw CH2OH up

O

OH

OH

OH

OH

CH2OH

1

2

3

4

5

6

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Glycolysis: Step #1

Kinases transfer PO32- groups from one molecule to another

Hexokinase

Mg2+

Reaction mostly proceeds to the right

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Glycolysis: Step #2

Phosphoglucose Isomerase (PGI) converts G6P into a fructose-based molecule through acid-base catalysis

Let’s look at this mechanism more closely…

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PGI Reaction Mechanism

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PGI Reaction Mechanism

BaseCatalysis

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PGI Reaction Mechanism

AcidCatalysis

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PGI Reaction Mechanism

H+

Base catalyzes ring closure

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Practice Drawing Fructose 6-Phosphate

Begin with the ring system

O

2

34

1

5

6

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Practice Drawing Fructose 6-Phosphate

Add Substitutents

C1 = CH2OH drawn up C2 - draw OH down C3 - draw OH up C4 - draw OH down C6 = CH2OPO3

2- drawn upBegin with the

ring system

O

2

34

1

5

6

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Glycolysis: Step #3

PFK

+ ADP + H+

Phosphofructokinase transfers PO32- group from

ATP to fructose-6-phosphate

So far, 2 ATP molecules have been invested in glycolysis!

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Drawing FBP

Recall from Ch. 8

Haworth and Fischer projections are equivalent

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Glycolysis: Step #4

Aldolase

Aldolase is unique in glycolysis; it cleaves FBP into two 3-C molecules - GAP and

DHAP

Let’s see how aldolase works…

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Aldolase Rxn Mechanism

Aldolase binds to the substrate Fructose-1,6-Bisphosphate

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Aldolase Rxn Mechanism

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Aldolase Rxn Mechanism

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Aldolase Rxn Mechanism

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Aldolase Rxn Mechanism

H2O

Aldolase cleaves FBP into GAP and DHAP

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Glycolysis: Step #5Triose Phosphate Isomerase

DHAP must be converted into

GAP via the enzyme triose phosphate isomerase (TIM)

to proceed through glycolysis

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Overview After Step 5

Two molecules of ATP are invested initially.

One molecule of glucose gets metabolized into 2

molecules of GAP

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Next Week…

• Steps #6-10 of glycolysis

• Overview of bioenergetics from glycolysis

• More on enzymes in glycolysis