BCH 361 Lecture 1: Glucose Metabolism

128 views8 pages
13 Feb 2017
Department
Course
Professor

For unlimited access to Class Notes, a Class+ subscription is required.

Glucose metabolism: Transform E in chemical bonds of glucose into chemical bonds of ATP. ATP used by cells; creating
electrochemical gradient using membrane pumps, contracting muscle.
Process is anaerobic - doesn't require o2
Lactate fermentation = lactate (our body)
Ethanol fermentation = ethanol
Under anaerobic conditions, pyruvate undergo fermentation.
Glycolysis: glucose in cytoplasm broken down to 2 pyruvate and net 2 ATP molecules.
When ATP high = Pyruvate and lactate transformed back into glucose via gluconeogenesis --> glycogen.
High ATP =gluconeogenesis; don't want to break down glucose. Glucose transformed into polysacch form, glycogen.
Low ATP =glycolysis.
Stage 1 traps glucose in cell and destabilizes its structure (=increase overall E = more reactive).
Stage 2 breaks down destabilized glucose into 2 components.
Stage 3 oxidize the 2 components to harvest E of the 2 molecules to form ATP, pyruvate and NADH molecules.
Step 1: Hexokinase phosphorylates glucose C6, creating glucose 6-phosphate (G6P)
Step 2: Phosphoglucose isomerase transforms G6P to fructose-6-phosphate, F6P.
Step 3: Phoshphofructokinase phosphorylates F6P to make fructose-1,6-bisphosphate, FBP.
In stage 1, glucose is transformed into fructose 1,6-bisphosphate (F1,6BP)
Stage 1 of Glycolysis (Steps 1, 2, 3)
Once glucose in inside cell inside, hexokinase phosphorylates C6 of glucose, creating G6P.
Gº' = -16.7 kJ/mol is negative and spontaneous under standard conditions = 1 of 3 regulated steps.
phosphorylates hexose sugars such as glucose.
allosteric enzyme - compound binds on site other than binding site.
inhibited by high concentrations of product.
Hexokinase - muscle
lower affinity for glucose and hexokinase. Not allosteric.
Activity not sig. unless there's high [glucose].
Glucokinase - liver
Both exhibit random BiBi kinetics.
Divalent metal ion, like Mg2+, interacts w/ ATP molecule = stablizes -ve charge, and changes ATP conformation to undergo rxn:
Step 1: Activation of Glucose
Transform G6P to fructose-6-phosphate (F6P) (aldose to ketose) by phosphoglucose isomerase (PGI).
Step 2: Formation of Fructose (Isomerize G6P --> Fructose)
Glucose Metabolism
Thursday, November 24, 2016
2:46 PM
BCH 361 Page 1
Unlock document

This preview shows pages 1-3 of the document.
Unlock all 8 pages and 3 million more documents.

Already have an account? Log in
Phosphoglucose isomerase (PGI) opens up G6P into its open-chain conformation so that the reactive aldehyde group is exposed
(cyclic forms don't undergo rxns bc the aldehyde or ketone group is not exposed).
1.
Open chain fructose-6P -> Cyclic fructose-6P.
2.
= More unstable = Break down to 2 components in Stage 2.
Fructose is phoshporylated by phosphofructokinase (PFK), forming fructose-1,6-bisphosphate (FBP).
So far, 2 ATP molecules used, no ATP produced yet.
Second activation commits the molecule to glycolysis process.
PFK-1 is highly regulated
Step 3: Second Activation (Phosphorylate Fructose)
The substrate binds.
1.
An enzymatic acid, probably the ε-amino group of a conserved
2.
Lys residue, catalyzes ring opening.
A base, thought to be a His imidazole group, abstracts the acidic
3.
proton from C2 to form a cis-enediolate intermediate (the proton
is acidic because it is to a carbonyl group).
The proton is replaced on C1 in an overall proton transfer.
4.
Protons abstracted by bases rapidly exchange with solvent protons.
Nevertheless, Irwin Rose confirmed this step by demonstrating
that [2-3H]G6P is occasionally converted to [1-3H]F6P by
intramolecular proton transfer before the 3H has had a chance to
exchange with the medium.
The ring closes to form the product, which is subsequently released
5.
to yield free enzyme, thereby completing the catalytic cycle.
BCH 361 Page 2
Unlock document

This preview shows pages 1-3 of the document.
Unlock all 8 pages and 3 million more documents.

Already have an account? Log in
PFK-1 is glycolytic, PFK-2 is not. PFK-2 functions as a kinase by phosphorylating F6P on position 2 to make F26BP + acts as
phosphatase.
Goal: Breaks down highly reactive FBP into two 3C molecules, glyceraldehyde 3-phosphate (GAP).
Aldolase: enzyme that catalyzes breakdown of FBP into 2 different 3C molecules, GAP and DHAP.
Triose phosphate isomerase
2 processes:
Stage 2 breaks down destabilized glucose into 2 components.
Aldolase catalyzes breakdown of F1,6B into 2 different 3C molecules, GAP and DHAP.
Fructose is cut bc of its symmetry and it’s energetically easier.
Gº' = +23.8 kJ/mol - standard free energy but can happen in cell bc [F1,6BP] is about 1x10^-4 M.
Actual Gº' ~ 0.
*Note: Aldol cleavage between C3 and C4 of FBP requires a carbonyl at C2 and a hydroxyl at C4. Hence, the “logic” of Reaction 2 in
the glycolytic pathway, the isomerization of G6P to F6P, is clear. Aldol cleavage of G6P would yield products of unequal carbon chain
length, while aldol cleavage of FBP results in two interconvertible C3 compounds that can therefore enter a common degradative
pathway.
Aldol cleavage is catalyzed by stabilizing its enolate intermediate through increased electron delocalization.
Aldolases: Class I - Schiff Base, Class II - Divalent ion
Aldolase mechanism:
Step 4: Formation of Triose Phosphates
BCH 361 Page 3
Unlock document

This preview shows pages 1-3 of the document.
Unlock all 8 pages and 3 million more documents.

Already have an account? Log in

Get access

Grade+
$10 USD/m
Billed $120 USD annually
Homework Help
Class Notes
Textbook Notes
40 Verified Answers
Study Guides
1 Booster Class
Class+
$8 USD/m
Billed $96 USD annually
Homework Help
Class Notes
Textbook Notes
30 Verified Answers
Study Guides
1 Booster Class