Exam 3 Flashcards
Glycogen
Storage form of glucose. Highly branched structure.
Glycogenesis
The formation of glycogen from sugar. It takes place in the liver and muscle.
Glucose (using hexokinase) Glucose-6-P Glucose-1-P -> UDP-Glucose->GLYCOGEN (in muscle)
Glucose (using glucokinase) Glucose-6-P Glucose-1-P -> UDP-Glucose->GLYCOGEN (in liver)
Glucokinase is an isozyme and has a high Km value.
Consumes the free energy of UTP.
Glycogenolysis
The biochemical breakdown of glycogen to glucose.
Glycogen->Glucose-1-P->Glucose-6-P->GLUCOSE (liver)
Glycogen->Glucose-6-P->Glycolysis->ATP (Muscle)
Glycogen degradation
Glycogenin
An enzyme converting glucose to glycogen. A glycogen primer that glycogen synthesis needs.
Glucagon
Peptide hormone produced by alpha cells of the pancreas. Stimulates glycogen breakdown.
Gluconeogenesis
Synthesis of glucose from non-carbohydrate precursors (amino acids, lactate, glycerol); occurs in liver; occurs in fasting state; the reverse of glycolysis.
General overview to gluconeogenesis
RBC-lactate-pyruvate-oxaloacetate (glucogenic amino acids)-triose phosphate (DHP & GAP)-glucose.
Glucogenic amino acids are all acids except Leu and Lys. They are ketogenic.
Step 1
Pyruvate is converted in 2 steps.
Pyruvate is an a-ketoacid.
Pyruvate carboxylase takes a bicarbonate ion + ATP and releases ADP + Pi.
Oxaloacetate is formed (an acetate group on carbon 4). This conversion requires energy.
Phosphoenolpyruvate carboxykinase takes GTP and releases GDP + CO2.
Phosphoenolpyruvate is a 3 carbon chain with a phosphate group on carbon 2.
This is an irreversible step.
Pyruvate carboxylase uses ________ as a cofactor.
Biotin
Biotin is covalently attached to a _______ residue in the enzyme.
Lys (Lysine)
True/False
CO2 reacts with ATP such that some of the free energy released in the removal of ATP’s phosphoryl group is conserved in the formation of the “activated” compound carboxyphosphate.
True
Like ATP, _________ releases a large amount of free energy when its phosphoryl group is liberated.
Carboxyphosphate
In the pyruvate carboxylase mechanism, the enzyme abstracts a ______ from _______, forming a carbanion.
Proton; pyruvate
In the pyruvate carboxylase mechanism, the carbanion attacks the ________ group attached to ______, generating oxaloacetate.
Carboxyl; biotin
Step 2
Enolase
Converts (2) PHOSPHOENOLPYRUVATE (alkene) + H2O to (2) 2-PHOSPHOGLYCERATE
Reversible reaction
Enolase catalyze a dehydration reaction
Step 3
Phosphoglycerate mutase
Converts (2) 2-PHOSPHOGLYCERATE to (2) 3-PHOSPHOGLYCERATE
Reversible reaction.
Isomerase reaction
Step 4
Phosphoglycerate kinase
Converts (2) 3-PHOSPHOGLYCERATE + ATP to (2) 1,3-BISPHOSPHOGLYCERATE + ADP
Reversible reaction
Transferase reaction
1,3-bisphosphoglycerate is a high energy intermediate
Step 5
Glyceraldehyde-3-phosphate dehydrogenase
Converts (2) 1,3-BISPHOSPHOGLYCERATE + NADH plus H+ to GLYCERALDEHYDE-3-PHOSPHATE plus NAD+
Reversible reaction.
NADH plus H+ is oxidized to NAD+; phosphate group does not come from ATP.
Reaction is both a phosphorylation and an oxidation-reduction.
1,3-bisphosphoglycerate is a high energy intermediate.
Covalent catalysis (direct bond between enzyme and substrate)
Step 6
Triose phosphate isomerase
Converts glyceraldehyde-3-phosphate to Dihydroxyacetone phosphate
Isomerization reaction (moves a group or a double bond within the same molecule)
Reversible reaction
Can convert back and forth
Step 7
Aldolase
Converts GAP and DHP to fructose-1,6-bisphosphate
Reversible reaction
Aldolase is a lyase (cleaves to make the 2 molecules)
GAP and DHP have 3 carbons each. After condensation it makes 1, 6 carbon chain.
Step 8
Fructose-1,6-bisphosphatase
Converts Fructose-1,6-bisphospate and H2O to fructose-6-phosphate and Pi.
Irreversible step.
Removes the phosphate group on carbon 1.
#1 regulated step.
Step 9
Phosphoglucose isomerase
Converts fructose-6-phosphate to glucose-6-phosphate.
Reversible step
Step 10
Glucose-6-phosphatase
Converts glucose-6-phosphate and H2O to glucose and Pi.
Irreversible step
What would happen if glycolysis and gluconeogenesis occurred simultaneously?
There would be a net consumption of ATP. Goal of producing ATP would be futile. Instead, glycolysis and gluconeogenesis are regulated based on the cell’s needs.
Fructose-2,6-bisphosphate increases/decreases the activity of __________ and increases/decreases the activity of ____________.
Increases; phosphofructokinase; decreases; fructose-1,6-bisphosphatase
Precursor molecules for gluconeogenesis
Amino acids, lactate and glycerol. No carbohydrates
What enzyme is used to convert glucose to glucose-6-phosphate in glycogenesis in the liver?
Glucokinase; it is an isozyme; only happens in the liver. This enzyme takes longer to get saturated by the substrate (less efficient for binding to substrate).
Phosphoglucomutase
Converts glucose-6-phosphate to glucose-1-phosphate.
Reversible step.
Isomerase
Moves phosphate group from carbon 6 to carbon 1.
UDP-glucose pyrophosphorylase
Converts glucose-1-phosphate to UDP-glucose and hydrolyzes the 2 phosphate groups (pyrophosphate) as PPi. Inorganic pyrophosphatase converts it to 2 Pi.
UDP-glucose is the activated form of glucose.
The hydrolysis of inorganic pyrophosphate drives the reaction; dG=-19.2 KJ*mol-1 (exergonic).
Glycogen synthase
Converts UDP-glucose and glycogen to UDP + Glycogen (n+1 residues) which is an alpha-1,4-glycosidic bond. First molecule on the left, carbon 1 determines alpha or beta.
Glycogen used is an existing strand.
What is transglycosylase?
It’s a branching enzyme that cleaves off the seven residue segment and reattaches it to the glucose C6-OH to create an alpha-1,6 branch point.
Seven-residue segment is a 7-glucose strand.
How are linear chains in glycogen broken down?
Via phosphorolysis with the enzyme glycogen phosphorylase; makes glucose-1-P
How are branched chains in glycogen broken down?
Via hydrolysis with the enzyme glucose-6-phosphatase; yields glucose
Which step does glucose-6-phosphate enter in glycolysis for glycogenolysis in the muscle?
At step 2; it will be an inhibitor.
One less ATP is consumed in the muscle compared to glucose from the bloodstream;the net gain of ATP is higher (3 ATP instead of 2)
What type of receptor does glucagon use?
G-protein receptor.
What type of bonds are found in the active form of insulin?
Disulfide bonds; insulin is a zymogen and must be cleaved to be active.
How does insulin stimulate glycogen synthesis?
A ligand binds to the receptor tyrosine kinase, it is transported through the membrane where it goes through autophosphorylation (phosphorylation of the kinase by itself). ATP -> ADP (Kinase 1 goes from an inactive state to active). The active kinase 1 is phosphorylated by ATP kinase 2 goes from inactive to active. It then goes through changes in metabolic activity and gene expression.
How does glucagon stimulate glycogen breakdown?
A ligand binds to a G-protein receptor, the G-protein goes from inactive to active and is now a substrate that is bound to an enzyme. The substrate is broken down to a second messenger, cAMP. 3 alpha/beta subunits are target proteins.
Explain regulation of glycogen synthesis
Glucagon leads to phosphorylation of glycogen synthase. If glucagon is being released and phosphorylating glycogen synthase, you don’t want to make glycogen.