Lecture+10+F 11+Glycolysis

8/3/2019 Lecture+10+F 11+Glycolysis

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GlycolysisChapter 16.1-16.2

The first stages of metabolizing

sugars anaerobically

TCA Cycle

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Anaerobic and Aerobic Metabolism of

Glucose

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It is common to almostall organisms

The Glycolyticpathway splits a six

carbon sugar into two

3-carbon compoundsin three stages

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The FirstStage of

Glycolysis

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Stage 1

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Hexokinase uses Induced Fit

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Hexokinase Uses an Induced Fit

E + Glucose ES

Voet and Voet, Wiley

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Preparing for the split

Isomerase

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Aldolase is the enzyme that cleaves

the critical bond

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RO

R

+ R-NH3R

NHR

R H2O

Schiff Base

See pg 606 (582) for details

Aldolase reaction - retroaldol

condensation

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Triose phosphate isomerase interconvertsdihydroxyacetone phosphate and glyceraldehyde 3-phosphate

Two molecules of glyceraldehyde 3-phosphate can nowenter Stage 3 of glycolysis only one path to finish

Stage 2: Isomerization of Dihydroxyacetone

phosphate to glyceraldehyde 3-phosphate

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II

III

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Triose phosphate isomerase (TIM)

TIM-barrel

,-Barrel

Very stable and

common

kcat/Km = 2 x 108 M-1s-1 !!!

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TIM Mechanism

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Stage III is Productive!

No gain of energy

Here is the reward!

(2 ATP) x 2 + 2 NADH

2 ATP

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II

III

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Glyceraldehyde-3-P Dehydrogenase

This uses the favorable oxidation of an aldehyde to an acidto obtain NADH and a high energy phosphate - an

anhydride 18


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Glyceraldehyde 3- phosphate

dehydrogenase oxidizes and

phosphorylates with one enzyme Fig. 16.8, Stryer

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- 12 kcal/mol

+ 12 kcal/mol

Formed with an active site

cysteine residue during catalysis-

see Stryer, Figure 16.8

Energetics of 1,3 Bisphosphoglycerate Formation

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II

III

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1,3 BPG has a high phosphotransfer potential:G = -11.8 kcal/mole (hydrolysis)

In comparison, for ATPs phosphotransfer potential:G = -7.3 kcal/mole (hydrolysis)

Phosphoglycerate Kinase generates the first ATP

Acid phosphate-an anhydride

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Generating the last ATP molecule:

three enzymatic steps

Phosphoenolpyruvate has a high phosphotransfer potential:G = -14.8 kcal/mole (hydrolysis) 23


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Note that the G values in the last column, which are calculated for typical

concentrations of these compounds in the cell, are much more favorablethan the G

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TCA Cycle

More energy

Fate of Pyruvate

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Anaerobic Fermentation

Regenerates NAD+

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Read pgs 469-472 to

see how these

interconversions take

place

Entry of galactose and fructose into

the glycolytic pathway

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Energy Charge =[ATP] +1/2[ADP]

[ATP]+[ADP]+[AMP]

Normal energy charge

Adenylate kinaseAMP+ATP

ADP+ADP

The energy charge of a cell regulates

catabolic and anabolic reactions

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Regulation of phosphofructokinase is key

to regulating glycolysis

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Regulation of phosphofructokinase is key

to regulating glycolysis

Inhibition of phosphofructokinase by binding of ATP at allosteric regulatory sites30


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Regulation of Glycolysis

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Glycolysis Regulation

See Pg 454, Stryer32


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Regulation of Pyruvate Kinase:Allosteric and covalent modification (16.2)

Allosteric

Phosphorylation

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Glycolysis

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Glycolysis - Summary

Common to most organisms

NADH must be converted to NAD+ by various means

Glycolysis is tightly regulated in multiple ways

Regulation is at irreversible steps

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Lecture+10+F 11+Glycolysis

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