Biochemistry of Carbohydrates Part II
Dr. Kevin Ahern
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
Gluconeogenesis and Glycolysis • 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
Gluconeogenesis and Glycolysis • Regulation
Gluconeogenesis and GlycolysisGluconeogenesis • Regulation
Glycolysis
Gluconeogenesis and Glycolysis • 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
Gluconeogenesis and Glycolysis • Regulation
Cori Cycle
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 Metabolic Melody 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
Benny Beaver Song (to the tune of “Red River Valley”)
Copyright © Kevin Ahern
Metabolic Melody
In Corvallis a lovable mascot Wonders why he’s the way that he is Everyone that he meets has one answer It relates to the sequencing biz Engineers say that Benny’s amazing Building dams of incredible strength And his front teeth are worthy of praising Growing to an incredible length Why is our college mascot so daunting? While the others like ducks are so meek? DNA in the cells of our Benny Is what makes all of his traits unique So our Beaver will soon get his answers To the questions, revealing unknowns There will be all the info he’s after In the sequence of his full genome
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
Metabolic Melody 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