Lesson 12 - Glucogenesis & Glycogen Metabolism Flashcards
What kind of pathways are glycogen metabolism and gluconeogenesis
- reciprocally regulated pathways: one is the catabolism of glucose while the other is the anabolic “reverse”
glycolysis
literally means the “loosening of sugar” - it is the catabolic oxidation of 6-Carbon glucose to two 3-carbon molecules
gluconeogenesis
- synthesis of glucose from pyruvate (end product of glycolysis) and other glycolytic intermediates
- occurs by a series of reactions which reverse glycolysis with 3 exceptions
what enzymes are shared between glycolysis and gluconeogenesis
“near reactios”
- phosphoglucoisomerase
- aldolase
triose phosphate isomerase
- GADPH
- phosphoglycerate kinase
- phosphoglycerate mutase
- enolase
which enzymes are different when comparing glycolysis and gluconeogenesis
hexokinase, phosphofructokinase, pyruvate kinase
tissues that synthesize glucose
primarily the liver, a little bit of the kidney medulla
tissues that use glucose as their primary energy source
brain and nervous tissue, muscle, erythrocytes, testes
gluconeogenisis rxn: 1
Pyruvate + Co2 + ATP + H2O –> Oxaloacetate + ADP + Pi + H+
Enxyme: Pyruvate carboxylase
Glycolytic enzyme: pyrivate kinase
Reaction type: bypass rxn
gluconeogenisis rxn: 2
Oxaloacetate + GTP –> phosphoenolpyruvate + CO2 + GDP
Enzyme: Phosphoenolpyruvate carboxykinase
Glycolytic enzyme: pyrivate kinase
Reaction type: bypass rxn
gluconeogenisis rxn: 3
Phosphoenolpyruvate to 2-
Phosphoglycerate by Enolase
**requires addition of H2O*
gluconeogenisis rxn: 4
2-phosphoglyerate to 3-phosphoglycerate by phosphoglycerate mutase
gluconeogenisis rxn: 5
3-phosphoglycerate + ATP –> 1,3-Bisphosphate + ADP by phosphoglycerate kinase
gluconeogenisis rxn: 6
1,3-Bisphosphate + NADH + H+ –> glyceraldehyde -3-phosphate + Pi + NAD+ by GADPH
gluconeogenisis rxn: 7
glyceraldehyde -3-phosphate to dihydroxyacetone phosphate by triose phosphate isomerase
gluconeogenisis rxn: 8
dihydroxyacetone phosphate to fructose-1,6 bisphosphate by aldolase
gluconeogenisis rxn: 9
fructose-1,6 bisphosphate + H20 to fructose-6-phosphate + Pi by fructose-1,6-bisphosphatase-1
gluconeogenisis rxn: 10
fructose-6-phosphate to glucose-6-phosphate by phosphoglucose isomerase
gluconeogenisis rxn: 11
glucose-6-phosphate + H2O to glucose + Pi by glucose 6-phosphatase
bipass reactions
1,2,9,11
how many pyruvate do you need to synthesize 1 mol of glucose
2
what are the 4 major sources of carbon for glucose synthesis for gluconeogenesis
glycerol, CO2 fixation in chloroplasta, amimo acids, lactate
where does a lot of pyruvate come from
lactate
- lactate produced in muscle cells is transported to the liver and is converted to pyruvate by lactate dehydrogenase
pyruvate carboxylase requires what
the B vitamin, biotin (adds carbonyl group to pyruvate)
intermediate made from pyruvate carboxylase
carboxybiotin intermediate
what does bpg do
decreases the oxygen affinity of hemoglobin by binding in the central cavity of the deoxygenated form of hemoglobin
what happens if hexokinase mutated
[bpg] decreases, meaning the R state is more stabilized, higher affinity for oxygen, decreased p50 value, graph of oxygen saturation v. pO2 shifts to the left
- no glycolytic intermediates, including 2,3 bpg would accumulate
what happens if pyruvate kinase mutated
[bpg] increaes, meaning the T state is more stabilized, lower affinity for oxygen, increased p50 value, graph of O2 saturation v. pO2 shifts to the right
- all intermediates in stage II of glycolysis, including 2,3 bpg would accumulate
degradation of glycogen
the glycogen polymer can be broken down into individual glucose units which can then be targeted for glycolysis
why is the glycogen granule so highly branched and why is it a metabolic requirement for 55,000 glycogen units to be stored as a polymer instead of 55,000 individual glucose units?
[Glu] in the blood is about 5mM
- if 55,000 Glc stored as individual molecules in the cell, then intracellular [Glc] would approach molar quantities –> leading to buk H2O movement into the cell and the cell would explode
- storage as a long polymer prevents osmoregulatory problems and reduces effective conc. of glucose in the cell
- branching provides more surface area and “free ends” to degrade
structure of glycogen polymer
- long chains of glucose linked via alpha 1,4 glycosidic linkages
- with fewer intermittent branches being alpha 1,6 glycosidic linkages
key reactions in glycogen metabolism
1: Glycogen phosphorylase
2: Glycogen Synthase
3: glycogen branching and debranching enzymes
glycogen phosphorylase
Glucose n –> Glucose n-1 + G1P
** glycogen phosphorylase with PLP coenzyme
- most active part in glycogen metabolism
- this process is repetitive; the enxyme removes successive glucose redidues until it reaches the 4th glucose unit from a branch point
what does phosphoglucomutase catalyze
the interconversion of glucose 1-phosphate (from glycogen) and glucose 6 phosphae (near equilibrium)
glucose 6 phosphate in either the liver or muscle cells
in the liver cells: dephosphorylated and exported to those that need it
in the muscle cells: metabolized into glycolysis
how many ATP if glucose is imported from blood –> glycolysis
from blood glucose: net 2 ATP (-2 in phase 1 and +4 in phase II)
how many ATP if glucose unit comes from glycogen in the form of G1P –> glycolysis
from glycogen: Net 3 ATP (skip hexokinase: -1 in phase I and +4 in phase II)
Glycogen debranching enzyme
hydrolyze alpha 1 –> 4 transfer and synthesize alpha 1 –> 4
- group transfer top 3 glucose residues to the bottom
- adds H2O to alpha 1,6 branch
SUMM
- glycogen phosphorylase leaves ~ 4 glucose units (sterically inhibited from phosphorylizing “nub”)
- debranching enzyme is a transferase and a hydrolase
debranching enzyme: 2 steps, 3 reactions
1.) hydrolyze alpha 1 –> 4 glycosidic linkage (-15.5 KJ/mol)
2.) transfer branch and make an alpha 1 –> 4 glycosidic linkage (+15.5 KJ/mol)
3.) Hydrolyze last alpha 1 –> 6 glycosidic linkage (-7.1 KJ/mol)
what is the debranching delta G
-7.1 KJ/mol
what is the shared common enzyme between glycogen synthesis and breakdown
phosphoglucomutase
step 1 of glycogen synthesis
glucose-6-phosphate to glucose-1-phosphate by phosphoglucomutase
- readily reversible reaction
- if ATP snd NADH are high; store glucose unit
step 2 of glycogen synthesis
form a nucleotidyl-glucose intermediate
- adding a glucose requires the formation of a nucleotifyl-glucose intermediate
- this is an anabolic process
1- “molecularly” tages a G1P molecule for use in another metabolic process (UDP-Glc NOT a substrate for phosphoglucomutase)
2 - sequesters a pool of UDP - Glc for one metabolic fate
3- PPi is a good leaving group; 1Pi is exergonic
after the glycogen branching enzyme, how many ends are there
3 instead of 2
summary breakdown of glycogen in the liver
Glycogen –> G1P- –> G6P –> Free Glc –> to blood –> to muscles
summary breakdown of glycogen in the muscle
glycogen –> G1P –> G6P –> to glycolysis
deficiency in glucose 6 phosphate can cause what
enlarged liver –> cant breakdown glycogen
