BCHM-3050 Lecture Notes - Lecture 11: Pyruvate Carboxylase, Phosphoenolpyruvate Carboxykinase, Pasteur Effect
15 Jun 2018
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Pasteur Effect
Early discovery that led to major points of regulation
Glycolysis: depend on adenylate charge
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Involves the inhibition of glycolysis by oxygen
More energy derived from complete oxidation of glucose (ex. Krebs
cycle, ETC, etc) instead of glycolysis alone
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Use yeast that grows under anaerobic conditions
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Expose yeast to oxygen
Result: decrease in glucose utilization
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PFK: inhibited by high ATP
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Energy starvation: decrease ATP
Increase use of glycolysis to make more energy
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Glucose synthesis and use
Gluconeogenesis: the production of new glucose
Synthesis from noncarb precursors
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Need way to synthesize glucose
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Glycolysis in reverse
BUT need a way to get past bypasses
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Glucose = fuel for body
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Brain req 120 g/day
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Bypass #1:pyruvate carboxylase and phosphoenolpyruvatecarboxykinase
(PEPCK)
This is a two-parter
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rxn #1:
Pyruvate carboxylase catalyze carboxylation of pyruvate to oxaloacetate
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CO2 pops onto pyruvate
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Depends on biotin and ATP
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Pyruvate carboxylase req acetyl-CoA as allosteric activator
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Rxn #2:
PEPCK converts oxaloacetate, w help of GTP, to phosphoenolpyruvate
Take energy from breaking the phosphate bond to add phosphate to
oxaloacetate
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Rxn 1 and 2 are coupled to make an overall favorable rxn
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Bypass #2: fructose 1,6-bisphosphatase
Fructose- 1,6- bisphosphate is converted into fructose-6-phosphate via a
hydrolytic reaction catalyzed by fructose-1,6-bisphosphatase
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Fructose-1,6-bisphosphatase is isomerized to glucose-6-phosphate via
phosphoglucoisomerase
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Bypass #3; glucose-6-phosphatase
Glucose-6-phosphate is converted into glucose via hydrolysis with the
help of glucose-6-phosphate
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The phosphate is also lose
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Cori Cycle
Skeletal muscle: glycolysis
Make waste product of lactate
From anaerobic fate of pyruvate
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Made with help of NADH
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Liver: gluconeogenesis
Lactate is converted to pyruvate to participate in gluconeogenesis
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Regulation of glycolysis and gluconeogenesis
When one is on the other has to be off
Prevent futile cycles
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Also take in account need to maintain a plethora of intermediates for
biosynth purpose
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Glycogen is synthesized from UDP-Glc
Intermediate substrate = uridine diphosphate glucose (UDP-Glc)
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Synthesized from blood glucose
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Glycogen branches add by amylo(1,4-1,6) transglycoylase
amylo(1,4-1,6) transglycoylase: branching enzyme
Transfer 6 to 7 residue from branch terminus
At least 11 residue long
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Once chain gets 11 residue long the enzyme takes the last 6-7
residue and transfer back to original chain as a branch
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Control of glycogen synthesis activity
Unphosphorylated form of glycogen synthesis: exists primarily in active
form
R state
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Several kinases: phosphorylate glycogen
Convert back to inactive state
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Glucose: allosteric activator
Shift equilibrium of phosphorylated from form T state to R state
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Utilization of sugar other than glucose
Disaccharides
Lactose => galactose => Glucose-1-phosphate
Maltose => glucose => G6P
Mannose => mannose-6- phosphate => F6P
Sucrose => fructose => F6P
Fructose => fructose-1- phosphate => DHAP
Glyceraldehyde => GAP
Fat metabolism
Glycerol => glycerol-3-phosphate => DHAP
Glycosidic bond cleavage of disaccharide
Broken on non reducing end
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Disaccharide and polysaccharide can be cleaved two ways
Hydrolysis (cleave with water)
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Phosphorolysis (cleave with phosphate)
One of the monomers is left with a phosphate group
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Digestion of amylopectin and glycogen
Alpha amylase: cleave alpha (1=>4) linkage from nonreducing end (-OH)
Cant cleave alpha (1-6) linkage at a branch point
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Alpha (1-6)- glucosidase: debranch enzyme
Required to remove limit dextrin (semi-digested amylopectin)
Expose additional alpha (1-4) linked saccharides
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Glycogen utilization in cells
glycogen phosphorylase: cleave alpha (1-4) bond via phosphorolysis
Yield glucose-1-phosphate
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Debranching process in glycogen catabolism
Bifunctional glucotransferase catalyzes 2 rxns:
Transferase activity: transfer 3 to 4 glucose residue from limit
branch to non reducing end via a new alpha (1-4) linkage
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Alpha (1-6) glucosidase activity = remove remaining glucose
molecule
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Regulation of glycogen metabolism
Hormone binds to receptor
Release G protein which activates adenylate cyclase (AC) a.
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AC synthesizes cAMP
Binds the regulatory R subunit of PKA (protein kinase A)a.
Release the active C subunit PKA b.
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Active C subunit of PKA phosphorylates phosphorylase B kinase
Cause phosphorylase B kinase to activate a.
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Active phosphorylase B kinase converts inactive phosphorylase B to the
active Phosphorylase A
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Active phosphorylase A catalyzes glycogen breakdown 5.
Control of glycogen phosphorylase activity
In unphosphorylated form: glycogen phosphorylase exists in T state
Favored
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Phosphorylated form: primarily in the R state
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Allosteric effectors alter T-R equilibrium
Glucose, G6P and ATP push equilibrium to T state
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AMP push to R state
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Chapter 12: Part 2
Monday, June 11, 2018
6:12 PM
