Part II - Oregon State...

BiochemistryofCarbohydratesPartII

Dr.KevinAhern

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

XO2 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


• 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 Mitochondrion • 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 Realized by Not Regenerating ATP • Occurs in Endoplasmic Reticulum

Glucose 6 Phosphate (G6P) Glucose

Glucose-6-Phosphatase (G6Pase)

Glycolysis Enzyme Required ATP

GluconeogenesisandGlycolysis• Regulation

GlycolysisGlucose + 2 ADP + 2Pi + 2 NAD+

Yields 2 Pyruvate + 2ATP + 2 NADH + 2 H+ + 2 H2O

Gluconeogenesis2 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

CoriCycle

MetabolicMelody

Gluconeogenesisto the tune of "Supercalifragilisticexpialidocious"

Copyright © by Kevin Ahern

When cells have lots of ATP and NADH tooThey strive to store this energy as sugar yes they do

Inside of mitochondria they start with pyruvate(slow) Carboxylating it to make oxaloacetate

Oh gluconeogenesis is so exhilarating Memorizing it can really be exasperating

Liver cells require it so there’s no need for debatingGluconeogenesis is so exhilarating

Oh, glucose, glucose come to beGlucose, glucose come to be

Oxaloacetate has got to turn to PEPEmploying energy that comes from breaking GTP

From there it goes to make a couple phosphoglycerates(slow) Exploiting ee-nolase and mutase’ catalytic traits

Oh gluconeogenesis is liver’s specialtyProducing sugar for the body most admirablySix ATPs per glucose is the needed energy*

Gluconeogenesis is liver’s specialty

Oh glucose, glucose joy to meGlucose, glucose joy to me

Converting phosphoglycerate to 1,3BPGRequires a phosphate that includes A-T-P energyReduction with electrons gives us all an N-A-D(slow) And G3P’s isomerized to make D-H-A-P

Oh gluconeogenesis is anabolic blissReversing seven mechanisms of glycolysis

To do well on the final students have to learn all thisGluconeogenesis is anabolic bliss

Oh, glucose, glucose factoryGlucose, glucose factory

The aldolase reaction puts together pieces soA fructose molecule is made with two phosphates in tow

And one of these gets cleaved off by a fructose phosphatase(slow) Unless F2,6BP's acting blocking path-a-ways

Oh gluconeogenesis a pathway to revereThat makes a ton of glucose when it kicks into high gear

The cell's a masterminding metabolic engineerGluconeogenesis a pathway to revere

Oh glucose, glucose jubileeGlucose, glucose jubilee

From F6P to G6P, that is the final phaseThe enzyme catalyzing it is an isomerase

Then G6P drops phosphate and a glucose it becomes(slow) Inside the tiny endoplasmic-al reticulums

Oh gluconeogenesis is not so very hardI know that on the final we will not be caught off guard'Cause our professor lets us use a filled out index card

Gluconeogenesis is not so very hard

http://www.davincipress.com/professional.html

MetabolicMelody

BennyBeaverSong(tothetuneof“RedRiverValley”)

Copyright © Kevin Ahern

InCorvallisalovablemascotWonderswhyhe’sthewaythatheis

EveryonethathemeetshasoneanswerItrelatestothesequencingbiz

EngineerssaythatBenny’samazingBuildingdamsofincrediblestrength

AndhisfrontteethareworthyofpraisingGrowingtoanincrediblelength

Whyisourcollegemascotsodaunting?Whiletheotherslikeducksaresomeek?

DNAinthecellsofourBennyIswhatmakesallofhistraitsunique

SoourBeaverwillsoongethisanswersTothequestions,revealingunknownsTherewillbealltheinfohe’safterInthesequenceofhisfullgenome


MetabolicMelody

En-er-gy (To the tune of "Let It Be")

Copyright © Kevin Ahern

When I was walking through the forest

Grizzly bears came after me So I was badly needing

En-er-gyMy body dumped some epinephrine

Out into the blood for me 'Cause I was badly needing

En-er-gy

En-er-gy / En-er-gy En-er-gy / En-er-gy I was badly needing

En-er-gy

The epinephrine gave a kick to Enzymes deep inside of me To make a bunch of cyclic

AMPAnd when this hit my protein kinase

Catalytic ecstasy The C subunits started

Adding P's

Adding P's, adding P's Adding P's, adding P's Phosphorylation city

Adding P's

The protein kinase put a phosphate Onto PBK for meUsing energy from

ATP

And PBK in turn converted 'b's to 'a's and 'I's to 'D's *

So I released a ton of G1P

G1P / energy G1P / energy

California needs some G1P

And when the chaos had subsided I consumed some Frito Lays Which soon began reversing

These pathwaysThe glucose halted epinephrine

Insulin began the race to Turn on Phosphoprotein

Phosphatase

Phosphatase - cleaves the P's Phosphatase - cleaves the P's

The dephosphorylation Cleaves the P's

And so they were removed from action Cellular kinases

Thanks to Phosphoprotein Phosphatase

I'll end my story here before I Get depressed from one last fact

That dephosphorylation Favors fat

Favors fat, favors fatFavors fat, favors fatDephosphorylation

Favors fat


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