BCHM-3050 Lecture Notes - Lecture 12: Schiff Base, Aldehyde, Cyclic Adenosine Monophosphate

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Chapter 12: Carbohydrate Metabolism
Overview of Carbohydrate Catabolic and Anabolic Processes
The breakdown of glucose via glycolysis is the beginning of the generation of a large amount of ATP
per molecule of glucose.
Gluconeogenesis includes the synthesis of polysaccharides (glycogen)
Catabolism: the process of breaking large, complex macromolecules down to their simplest parts.
oEnergy is released
oReactions are oxidative
Anabolism: Opposite of catabolism. The building up and synthesis of large macromolecules and the
storing of energy.
oEnergy is required
oReactions are reductive
**Glycolysis as a whole is a catabolic reaction**
What to Know for Each Reaction
Major structures of substrates/products
Enzymes (name and abbreviations)
Basic Thermodynamics
Alpha Glucose
6 carbons
Cyclic
OH on the C#1
Alpha Fructose
Furanose (5 membered ring)
Anomeric center is at C#2
Glycolysis Overview
Phase 1: Energy Investment
oStart with glucose and prime it for a cleavage reaction by an aldilase. To cleave this product,
you have to add phosphate groups, and to do this, you have to have energy. Product of one
reaction becomes the substrate of the next reaction.
oGlyceraldehyde moves on from #6.
Phase 2: Energy Generation
oUse energy invested in the first phase to make energy.
Glycolysis: Reaction 1
Hexokinase (HK) – 1st ATP investment
oAlpha D glucose is converted to alpha glucose 6 phosphate (G6P).
oΔ G = -18.4 kJ/mol
o**IS THE FIRST IRREVERSIBLE PROCESS**
oMagnesium helps to coordinate and help with cleavage.
oIs a phosphorylation reaction and TAKES ENERGY – ATP helps to power the cleavage.
The intracellular concentrations of substrates/products with VARY – meaning that the ΔG will vary.
Hexokinase isoforms have different substrate specificities and binding affinities.
oBroad Substrate Specificity: fructose/mannose. Low Km for isoforms 1, 2, and 3.
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** Low Km = high specificity **
oHigh Km for hexokinase IV (glucokinase)
Hexokinase IV contributes toward the role of the liver as a glucostat, which allows the liver to adjust
the rate of glucose utilization in response to varying blood glucose levels.
Glycolysis: Reaction 2
Glucose-6-Phosphate Isomerase
oG6P is isomerized to fructose-6-phosphate. Phosphate group is still on C#6, and isomerization is
from pyranose to a furanose ring (constitutional isomers)
oBreak oxygen bond and move to #2 Carbon.
oGo from hemiacetal group to hemiketal group.
oBecause we are breaking the bond, it can be alpha or beta with rotation.
IS REVERSIBLE
oΔG = +1.7 kJ/mol
Reaction 2/3 sets the stage for a symmetric aldol cleavage (RXN 4)
Glycolysis: Reaction 3
Phosphofructokinase-1 (PFK1) ~ (2nd ATP Investment)
oInvests another ATP molecule. PFK1 takes the fructose 6 phosphate (F6P) and add on a second
phosphate group to the #1 carbon of the fructose to make Fructose 1,6 bisphosphate (FBP)
oΔG = -15.9 kJ/mol
PFK1 (allosteric enzyme) is a major control point for glycolysis, and is referred to as a committed step
for glycolysis. **
PFK-1
Is one of the MOST IMPORTANT control/regulation points of glycolysis.
oThe PFK enzyme is a homotetramer (4 identical subunits)
oIt has 2 active sites and 4 allosteric sites
ATP is also an allosteric effector
o(ATP)/(ADP) or (ATP)/(AMP) ratios INCREASE
Its forward product (F-1,6-bP) acts as a non allosteric inhibitor and helps drive the reverse reaction for
gluconeogenesis via the gluconeogenic enzyme fructose-1,6-bisphophatase.
Activators (allosteric):
oADP
oAMP
oFruc-2,6-bP (feedforward stimulation)
Inhibitors (allosteric):
oATP
oPEP
oLOW pH
F2,6BP
Activates glycolysis and inhibits gluconeogenesis
Product of 2nd step in glycolysis is F6P.
PFK-2 are distinct from the enzymes found in glycolysis and gluconeogenesis.
PFK-2/FBPase-2
Regulating enzymes are regulated themselves.
BIFUNCTIONAL ENZYMES
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Document Summary

The breakdown of glucose via glycolysis is the beginning of the generation of a large amount of atp per molecule of glucose. Gluconeogenesis includes the synthesis of polysaccharides (glycogen) Catabolism: the process of breaking large, complex macromolecules down to their simplest parts: energy is released, reactions are oxidative. The building up and synthesis of large macromolecules and the storing of energy: energy is required, reactions are reductive. **glycolysis as a whole is a catabolic reaction** Phase 1: energy investment: start with glucose and prime it for a cleavage reaction by an aldilase. To cleave this product, you have to add phosphate groups, and to do this, you have to have energy. Product of one reaction becomes the substrate of the next reaction: glyceraldehyde moves on from #6. Phase 2: energy generation: use energy invested in the first phase to make energy. The intracellular concentrations of substrates/products with vary meaning that the g will vary.

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