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127 Cards in this Set
- Front
- Back
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description of gluconeogensis
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making NEW glucose (not from glycogen)
-opposite of glycolysis |
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role of gluconeogensis
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replenishes glucose that is consumed by glycolysis
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role of gluconeogensis in
1)liver 2)muscle |
1) maintains blood glucose level
2) replenishes glycogen consumed in earlier bursts of muscle activity |
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can skeletal muscle make glucose?
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no, can only go to G6P.. used to replenish/store glycogen
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where does glycolysis occur?
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cytoplasm
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what other sugars can enter glycolysis
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1) fructose directly
2) galactose after conversion to glucose |
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where does gluconeogensis occur?
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90 % liver
10% kidney |
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net energy result of glycolysis
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2 ATP
2 NADH (2 electrons each) |
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rate-determining step in glycolysis
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phosphofructokinase
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converts Glucose 6 Phosphate to Fructose 6 Phosphate
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Phosphoglucoisomerase
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Converts Fructose-6-Phosphate to Fructose 1,6 Bisphosphate
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Phosphofructokinase
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what is a major feedback inhibitor of PFK-1?
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ATP
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what is the effect of ATP on PFK-1?
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alters the Km of PFK-1 for substrate (Fructose-6-Phosphate)
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How is Km altered if Low ATP levels
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has low Km for F6P
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How is Km altered if High ATP levels?
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has high Km for F6P
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why does it make sense that ATP is negative inhibitor of PFK-1 activity?
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ATP is an inhibitor of making more ATP
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An intermediate of the TCA cycle that serves as a feedback inhibitor of glycolysis
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Citrate
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what type of change in pH would inhibit activity of PFK-1 (glycolysis)?
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a drop in pH (higher H+)...lactic acid generates H+....has risk of acidifying cell until it dies
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Activators of PFK-1 (glycolysis)
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AMP, ADP and P....all signal that the cell needs more ATP production
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catalyzes reaction of
ATP + AMP = 2 ADP |
Adenylate Kinase
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what is the sensitive indicator that ATP is being used?
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AMP
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Major allosteric regulator of PFK-1....regulatory molecule and not a metabolic intermediate
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Fructose-2,6- Bisphosphate
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Sets the overall rate of glycolysis
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Fructose-2,6- Bisphosphate
(sets rate of glycolysis by setting rate of PFK-1) |
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what is the concentration of Fructose-2,6-Bisphosphate regulated by?
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hormonally regulated by the balance between glucagon and insulin in the liver
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how does Fructose-2,6-Bisphosphate work?
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modulates the km of PFK-1 for it's substrate, Fructose 1,6- Phosphate and it's inhibition by ATP
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what happens to ATP inhibition in the presence of Fructose-2,6- Bisphosphate?
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ATP's inhibition is decreased
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what forms Fructose-2,6- Bisphosphate?
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phosphofructokinae 2 (PFK-2) using Fructose-6-Phosphate as substrate
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What breaks down Fructose-2,6-Bisphosphate to Fructose-6-Phosphate and P?
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Fructose Bisphosphatase 2
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two enzymes contained in a single bifunctional enzyme that regulate Fructose-2,6- Bispohspate
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PFK-2 and Fructose Biphosphatase (FBPase-2)
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PFK-2 and FBPase-2 contain what three domains?
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regulatory domain
kinase domain phosphatase domain |
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kinase and phosphatase activites of PFK-s and FPBase are allosterically regulated by what? covalently regulated by what?
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Fructose-6-Phosphate
Phosphorylateion of a single serine residue by a protein kinase |
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In the liver, what occurs on the regulatory domain of PFK-2 and FBPase-2?
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serine residue is located right on regulatory domain- covalenly regulates the activity
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what is the effect of glycogen on PFK-2 and FBPase 2?
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phosphorylates complex and activates FBPase-2...glycolysis slows down and gluconeogenesis is stimulated
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Inslulin's effect on F-2,6-Bisphosphate?
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increases levels and stimulates liver glycolysis to clear up glucose from the blood.
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Fuction of Aldose
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Creates a ketone (Dihydroxyacetone Phosphate) and an aldehyde (Glyceraldehyde 3 Phosphate)...later will be used in glycolysis
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converts DHAP and GAP
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TRIOSE PHOSPHATE ISOMERASE
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importance of TRIOSE PHOSPHATE ISOMERASE
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without this enzyme, only half of each glucose molecule would proceeed through glycolysis..no net ATP production
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First step of generating energy in glycolysis
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Glyeraldhyde 3 Phosphate converted to 1, 3 Bisphosphglycerate by GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
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importance of GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE
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Generates NADH
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what is GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE inactivated by?
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heavy metals- Cysteinse SH group
-Arsenate Poisoning- (Arsenate resembles P) |
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What resembles Phosphate and has potential to poison GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE?
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Aresenate
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which enzyme harvests the energy of the very high energy anhydride bond?
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PHOSPHOGLYCERATE KINASE
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what kind of bond is formed when NAD is reduced to NADH?
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Very high energy ANHYDRIDE BOND when Glyceraldehyde-3-P is oxidized to a carboxylate.
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Enzyme involved in first production of ATP (substrate level phosphorylation)
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PHOSPHOGLYCERATE KINASE
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PHOSPHOGLYCERATE KINASE hydrolyzes which compound to generate ATP?
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1,3- Bisphosphoglycerate
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what is product formed when ATP is produced by hydrolization of high energy anhydride bond?
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3-Phosphoglycerate
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How is hemoglobin regulation related to glycolysis?
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1,3 Bisphosphoglycerate can be converted to 2,3 Bisphosphoglycerate, which is a regulatory molecule of hemoglobin for Oxygen affinity
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How can 2,3 Bisphosphoglycerate re-enter glycolysis?
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2,3 Bisphosphoglycerate Phosphatase converts it back to 3-Phosphoglycerate
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What is the role of Phosphoglycerate Muatase
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Converts 3 Phosphoglycerate- 2 Phosphoglycerate
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what is converted the enzyme that converts 2-Phosphoglycerate to Phosphoenolpyruvate?
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ENOLASE
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what drives the reaction that uses ENOLASE?
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release of water
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what is the high energy compound formed that will generate second ATP?
(formed from what low energy compound)? |
Phosphoenolpyruvate
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Role of PYRUVATE KINASE
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phosphoenolpyruvate to pyruvate
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Seocond IRREVERSIBLE/ KEY step in glycolysis
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PYRUVATE KINASE
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PYRUVATE KINASE is subject to feedforward activateion by what?
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Fructose-1,6-Bisphosphate...allows regulation of the two irreversible stes in glycolysis
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PYRUVATE KINASE is subject to feedback inhibition by what molecules
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ATP
ALANINE |
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How does ALANINE inhibit PYRUVATE KINASE?
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signals for pprotein degregation and utilization of amino acids by gluconeogenesis.
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why is ATP and Alanine regulation important in muscle cells?
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only want to be running glycolysis in muscles when they are using energy
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why does liver run glycolysis even in an ENERGY RICH state?
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to convert to pyruvate- to store fat
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Is PYRUVATE KINASE active or inactive when phosphorylated?
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INACTIVE
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what reactivates PYRUVATE KINASE?
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pp1 through dephosphorylation
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pp1 wants...
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glycogen synthesis
pyruvate (clears blood glucose) |
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What covalently regulates LIVER Pyruvate Kinase?
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cAMP- dependent Protein Kinase
(Protein Kinase A)- inhibits PYRUVATE KINASE- slows down glycolysis |
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Two ways that cAMP dependent protein kinase slows down glycolysis
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1) causes decreased levels of F-2,6-Bisphosphate when stimulated by glucagon to phosphorylate bifunctional enzyme
2) inhibits PROTEIN KINASE, which slows down glycolysis |
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which enzyme helps to regenerate NAD+ in the cell under anaerobic conditions?
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Lactate Dehydrogenase
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negative side of converting lactate to pyruvate?
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make lactate and the H+ that comes with it...makes cell VERY acidic!
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How is NAD+ regenerated under anerobic conditions?
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Shuttling the reducing equivalents (electrons, but not NADH itself) into the mitochondrion for subsequent oxidative phosphorylation
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How does fructose enter glycolysis in tissues other than the liver?
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HEXOKINASE converts it to Fructose-6-Phosphate
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What other role does Hexokinase play besides phosphorylating glucose?
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phosphorylates Fructose- Fructose-6-Phosphate so that it can enter glycolysis
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why doesn't glucokinase convert Fructose to Fructose-6-Phosphate?
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too much glucose to compete with
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enzyme that phosphorylates Fructose in the Liver?
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Fructokinase
*** requires ATP |
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how does fructose usually enter glycolysis if coming from liver?
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Glyceraldehyde-3-Phosphate
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Fructokinase converts Fructose to what?
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Fructose-1-Phosphate
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What initially happens to Fructose-1-Phosphate?
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Fructose 1-Phosphate Aldolase converts it to GLYCERALDEHYDE and DIHYDROXYACETONE PHOSPHATE
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What converts Glyceradledhye (from fructose) to Glyceraldehyde-3-Phosphate?
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Triose Kinase (requires ATP)
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What converts Dihydroxyacetone Phosphate (from fructose) to Glyceraldehyde 3 Phosphate?
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TRIOSE PHOSPHATE ISOMERASE (same as glycolysis)
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Four imporant enzymes for fructose
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1) FRUCTOKINASE (phosphorylates)
2)FRUCTOSE 1-P ALDOLASE 3)TRIOSE PHOSPHATE ISOMERASE 4)TRIOSE KINASE |
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What happens if there is a deficiency in FRUCTOSE-1-PHOSPHATE- ALDOLASE?
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Phosphate Depletion Disorder....cell doesn't have unlimited supply of P...all of P would be used up in Fructose-1-P....not enough Ps to make ATP
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how does galactose enter glycolysis?
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As GDP
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what converts UDP Galactose to UDP glucose?
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EPIMERASE (switches 1 OH group)
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Glycolysis is stimulated by_______ and inhibited by________
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INSULIN, GLUCAGON
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how do insluin and glucagon regulate glycolysis?
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regulating at the level of protein phosphorylation
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Where are the 3 IMPORTANT glucagon sites of action?
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1) glucokinase
2) PFK-2 3) pyruvate kinase (LIVER ONLY)....stimulates cAMP dependent protiein kinase to slow down glycolysis |
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how does glucagon act? via which protein?
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cAMP-dependent Protein Kinase
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what is the clinical presentation of defects of glycolysis? and why?
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hemolytic anemia...rbc's have no other alternative way to make energy
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where do most of mutation in glycolysis occur?
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pyruvate kinase
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what is the one thing you CANNOT make glucose from?
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fatty acids
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what is the part of triglycerides that can be converted to glucose when in starvation mode?
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glycerol
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substrates for gluconeogenesis in times of prolonged fasting (4)
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lactate
pyruvate glycerol alpha-ketoacids |
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glucogenic amino acid
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can be degraded to molecules that can be converted to glucose
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ketogenic
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amino acids that make ketones (lead to Acetyl CoA)....Lysine and Leucine
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IRREVERSIBLE STEPS IN GLYCOLYSIS
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Glucose- G6P
Fructose- Fructose 1,6-Bisphosphate Phosphoenolpyruvate-Pyruvate |
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Four enzymes involved in Gluconeogensis
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1)Pyruvate Carboxylase
2)PEP Carboxylase 3) Fructose 1,6- Bisphosphatase 4)Glucose 6 Phosphatase |
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Role of Pyruvate Carboxylase
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converts pyruvate to oxaloacetate
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where does Pyruvate Carboxylase work?
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in mitochondrial matrix
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what is the coenzyme used by Pyruvate Carboxylase?
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Biotin
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Frunction of Biotin
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coeenzyme that adds CO2
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difference between oxaloacetate and pyruvate?
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oxaloacetate has extra CO2 (carboxyl group)
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oxaloacetate can't get out of mitochondrial matrix, so what is done?
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is conerted to MALATE or ASPARTATE
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enzyme that converts Oxaloacetate to Malate? What is Produced?
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MITOCHONDRIAL MALATE DEHYDROGENASE
-NADH- NAD+ |
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enzyme that converts Oxaloacetate to Apartate?
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ASPARTATE AMINOTRANSFERASE
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what is the function of malate and aspartate?
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used by oxaloacetate to cross the mitochondral membrane in gluconeogensis
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malate is oxidized or reduced to oxaloacetate?
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oxidized
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oxaloacetate is oxidized or reduced to malate?
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reduced
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enzyme that converts Aspartate back to Oxaloacetate?
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Aspartate Aminotransferase (same as other way)
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enzyme that converts malate back to oxaloacetate?
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Cystolic Malate Dehyrdrogenase
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Cystolic Oxaloacetate is converted into what?
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PEP
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Function of PEP Carboxykinase
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converts Oxaloacetate to PEP
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what is used to decarboxylate Cystolic Oxaloacetate?
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GTP, CO2
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what is the expenisve reation in gluconeogensis that generates a very high energy intermediate?
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PEP Carboxykinase
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why it is believed that ASPARTATE is used instead of MALATE to get out of the mitochondrial matrix?
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doesn't use up any NADH in the matrix and didn't make any extra NADH in the cytosol
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when going backwards, PEP goes through glycolysis pathway until reaches what step?
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PFK-1
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what is inactivated during gluconeogenesis to prevent futile cycling?
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Liver's PYRUVATE KINASE
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when do you generate an NADH in gluconeogensis?
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when converting Lactate- Pyruvate
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fate of lactate in gluconeogenesis
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1) released by skeletal muscle
2) taken up by liver and converted to pyruvate 3) pyruvate is sent to mitochondral matrix to be converted to PEP |
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What is the hydrolytic enzyme that overcomes the second irreversible step in gluconeogenesis?
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FRUCTOSE-1,6-BISPHOSPHATASE
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what stimulates gluconeogenesis?
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glucagon-cAMP dependent protein kinase- FBPase2- GLUCONEOGENESIS
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during strenuous excersice what keeps energy in muscles when aerobic glycolysis cannot continue?
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CORI CYCLE
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what is a VERY POTENT inhibitor of gluconeogenesis?
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Fructose-2,6-Bisphosphate
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What inhibitis Fructose-1,6-Bisphoshatase?
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Fructose-2,6-Bisphosphate
AMP (signal for poor energy state) |
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what activates Fructose-1,6-Bisphoshatase?
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ATP (signal for energy-rich state)
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what overcomes the last irreversible step in gluconeogenesis?
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Glucose-6-Phosphatase
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fxn of GLUCOSE-6-PHOSPHATASE?
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releases free glucose from G6P
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where does GLUCOSE-6-PHOSPHATSE reside?
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only in liver, not in muscles!
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precursor for gluconeogensis in the liver
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PYRUVATE
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energy requirement for gluconeogenesis
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6 ATP
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high energy bond in gluconeogenesis is found in which compound?
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PEP
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