9. glycolysis-eclass

8/2/2019 9. Glycolysis-eClass

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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

9. glycolysis-eclass

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