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