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BiochemistryofCarbohydrates
PartII
Dr.KevinAhern
Glycolysis
• Summary
Glucose + 2 ADP + 2Pi + 2 NAD+
Yields
2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
Glucose
Product of Process
Glycolysis
• Fermentation in Yeast/Bacteria
GA3P
NAD+
X
NADH + H+
O2 Helps to
Make NAD+
1,3 BPG
In Absence of Oxygen
Pyruvate
(PYR)
Glycolysis
• Fermentation in Yeast/Bacteria
Glucose
Product of Process
Glycolysis
• Fermentation in Animals
GA3P
NAD+
X
NADH + H
+
1,3 BPG
Pyruvate
(PYR)
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
Reduced Quantities in Adults Leads to Lactose Intolerance
Lactase
Lactose
Galactose
Glucose
Glycolysis
• Metabolism of Other Sugars - Fructose
Fructokinase
Fructose
Fructose-1-Phosphate
(F1P)
Fructoaldolase
F1P
DHAP + Glyceraldehyde
Glyceraldehyde-3-Phosphate
To Glycolysis
Fructose
Regulatory Enzyme Bypassed
Glycolysis
• Metabolism of Other Sugars - Fructose
Regulatory Enzyme Bypassed
F1P
DHAP + GA3P
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
G6Pase
(Hexokinase)
F1,6BPase
(PFK)
PEPCK
Pyruvate Carboxylase
(Pyruvate Kinase)
Glucose
Gluconeogenesis 11. Glucose-6-Phosphatase
1. Hexokinase
• Reactions of Gluconeogenesis
G6P
10. Phosphoglucoisomerase
2. Phosphoglucoisomerase
F6P
9. F1,6 Bisphosphatase
3. PFK1
F1,6BP
8. Aldolase
4. Aldolase
DHAP + G3P
7. Triose Phosphate Isomerase 5. Triose Phosphate Isomerase
GA3P
6. GA3PDH
6. GA3PDH
Run as Reverse of
1,3 BPG
Glycolysis Reactions
5. Phosphoglycerate Kinase
7. Phosphoglycerate Kinase
3-PG
4. Phosphoglycerate Mutase
8. Phosphoglycerate Mutase
2-PG
3. Enolase
9. Enolase
PEP
2. PEPCK
10. Pyruvate Kinase
1. Pyruvate Carboxylase Pyr
Gluconeogenesis
• Reactions of Gluconeogenesis
• Reaction #1
• Step 1 of Bypassing Pyruvate Kinase
• Occurs in Mitochondrion
Gluconeogenesis
• Reactions of Gluconeogenesis
• Reaction #1
• Step 1 of Bypassing Pyruvate Kinase
• Occurs in Mitochondrion
Pyruvate Carboxylase
Pyruvate
(Pyr)
Oxaloacetate
(OAA)
Gluconeogenesis
• Reactions of Gluconeogenesis
CO2
Biotin Carrying CO2
Gluconeogenesis
• Reactions of Gluconeogenesis
• Reaction #2
• Occurs in Mitochondrion
• Second Triphosphate Necessary
Phosphoenolpyruvate Carboxykinase
(PEPCK)
Oxaloacetate
(OAA)
Phosphoenolpyruvate
(PEP)
Gluconeogenesis
• Reactions of Gluconeogenesis
• Reaction # 9 of Gluconeogenesis
• Not the Reversal of the PFK Reaction
• Energy Realized by Not Regenerating ATP
Glycolysis Enzyme Required ATP
Fructose 1,6 Bisphosphatase
(FBPase)
Fructose 1,6 Bisphosphate
(F1,6BP)
Fructose 6 Phosphate
(F6P)
Gluconeogenesis
• Reactions of Gluconeogenesis
• Reaction # 11 of Gluconeogenesis
• Not the Reversal of the Hexokinase Reaction
• Energy Realized by Not Regenerating ATP
• Occurs in Endoplasmic Reticulum
Glycolysis Enzyme Required ATP
Glucose-6-Phosphatase
(G6Pase)
Glucose 6 Phosphate
(G6P)
Glucose
GluconeogenesisandGlycolysis
• 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
GluconeogenesisandGlycolysis
• Regulation
GluconeogenesisandGlycolysisGluconeogenesis
• Regulation
Glycolysis
GluconeogenesisandGlycolysis
• Regulation
Reciprocal Regulation
Low Energy
High Energy
Other
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 (+)
F2,6BP is Made Upon Insulin Stimulation - Favors Glycolysis
F2,6BP is Broken Down Upon Glucagon Stimulation - Favors Gluconeogenesis
GluconeogenesisandGlycolysis
• Regulation
CoriCycle
Gluconeogenesis
to the tune of "Supercalifragilisticexpialidocious"
Copyright © by Kevin Ahern
The aldolase reaction puts together pieces so
A fructose molecule is made with two phosphates in tow
MetabolicMelody
gluconeogenesis
liver’s
specialty
And one of Oh
these
gets cleaved offis by
a fructose
phosphatase
Producing
sugar foracting
the body
most admirably
(slow)
Unless F2,6BP's
blocking
path-a-ways
When
cellsper
have
lots ofisATP
and NADH
too
Six ATPs
glucose
the needed
energy*
They strive
to store this energy
as sugar
yes they do
liver’s
specialty
Oh Gluconeogenesis
gluconeogenesis aispathway
to revere
Inside of mitochondria they start with pyruvate
That makes a ton of glucose when it kicks into high gear
(slow) Carboxylating
it to make
glucose, glucose
joy oxaloacetate
to me
The cell'sOh
a masterminding
metabolic
engineer
Glucose, glucose
joy totome
Gluconeogenesis
a pathway
revere
Oh gluconeogenesis is so exhilarating
Memorizing
it can really be exasperating
Converting
phosphoglycerate
to 1,3BPG
Oh glucose, glucose jubilee
Liver
cells require
it so there’s
no need for debating
Requires
a Glucose,
phosphate
that includes
glucose
jubileeA-T-P energy
Gluconeogenesis
is gives
so exhilarating
Reduction
with electrons
us all an N-A-D
(slow)
And
G3P’s
isomerized
to final
makephase
D-H-A-P
From
F6P
to G6P,
that is the
Oh, glucose, glucose come to be
The enzyme catalyzing it is an isomerase
Glucose,
glucose iscome
to be
Ohdrops
gluconeogenesis
Then G6P
phosphate and
aanabolic
glucosebliss
it becomes
Reversing
seven
of glycolysis
(slow)
Inside the
tinymechanisms
endoplasmic-al
reticulums
Oxaloacetate
got to turn
To do well
on the finalhas
students
havetotoPEP
learn all this
Employing
energy that comes
from breaking
GTP
Gluconeogenesis
is
anabolic
bliss
Oh gluconeogenesis is not so very hard
From there it goes to make a couple phosphoglycerates
I know that on the final we will not be caught off guard
(slow) Exploiting
ee-nolaseglucose
and mutase’
catalytic traits
Oh, glucose,
factory
'Cause our professor
lets us use a filled
out index card
Glucose, glucose
factory
Gluconeogenesis
is not so
very hard
BennyBeaverSong
(tothetuneof“RedRiverValley”)
Copyright © Kevin Ahern
MetabolicMelody
InCorvallisalovablemascot
Wonderswhyhe’sthewaythatheis
Everyonethathemeetshasoneanswer
Itrelatestothesequencingbiz
EngineerssaythatBenny’samazing
Buildingdamsofincrediblestrength
Andhisfrontteethareworthyofpraising
Growingtoanincrediblelength
Whyisourcollegemascotsodaunting?
Whiletheotherslikeducksaresomeek?
DNAinthecellsofourBenny
Iswhatmakesallofhistraitsunique
SoourBeaverwillsoongethisanswers
Tothequestions,revealingunknowns
Therewillbealltheinfohe’safter
Inthesequenceofhisfullgenome
En-er-gy (To the tune of "Let It Be")
Copyright © Kevin Ahern
When I was walking through the
forest
And PBK in turn converted
MetabolicMelody
Grizzly bears came after me
'b's to 'a's and 'I's to 'D's * So I was badly needing
So I released a ton of
En-er-gy
G1P
My body dumped some epinephrine
Out into the blood for me
G1P / energy
'Cause I was badly needing
G1P / energy
I'll end my story here before I
En-er-gy
California needs some
Get depressed from one last fact
G1P
En-er-gy / En-er-gy That dephosphorylation
En-er-gy / En-er-gy
And when the chaos had subsided
I was badly needing
Favors fat
I consumed some Frito Lays
En-er-gy
Which soon began reversing
These pathways
Favors fat, favors fat
The epinephrine gave a kick to
The glucose halted epinephrine
Enzymes deep inside of me
Favors fat, favors fat
Insulin began the race to
To make a bunch of cyclic
Turn on Phosphoprotein
Dephosphorylation
AMP
Phosphatase
And when this hit my protein kinase
Favors fat
Catalytic ecstasy
Phosphatase - cleaves the P's
The C subunits started
Phosphatase - cleaves the P's
Adding P's
The dephosphorylation
Cleaves the P's
Adding P's, adding P's
Adding P's, adding P's
And so they were removed from action Phosphorylation city
Cellular kinases
Adding P's
Thanks to Phosphoprotein
Phosphatase
The protein kinase put a phosphate
Onto PBK for me
Using energy from ATP