Gluconeogenesis Flashcards
gluconeogenesis
- depends on what precurors
- occurs in what tissues?
- is especially important for what tissues?
- synthesis of glucose from:
- pyruvate
- lactate
- alanine
- glycerol
- propionate
- takes place in the:
- liver (90%)
- kidney (10%)
- is key for:
- brain
- RBCs
what are the irreversible steps of gluconeogenesis?
- pyruvate –> OAA
- OAA –> PEP
- the subsequent glycolytic steps that are irreversible:
- F-1,6-BP –> F-6-P
- G-6-P –> glucose
pyruvate –> OAA
- catalyzed by what enzyme?
- in what part of the cell?
- requires what substrates and cofactors?
- regulated by?
- enzyme: pyruvate carboxylase (in the mitochondria)
- requires:
- ATP
- biotin
- regulated by: acetyl CoA
biotin
has a key role in what gluconeogenic step?
how does it work?
- pyruvate –> OAA (1st irreverisble step)
-
biotin serves as a carrier for activated CO2:
- CO2-biotin-pyruvate carboxylase complex forms using energy from ATP hydrolysis
- activated CO2 transferred to pyruvate to form OAA
what is the next gluconeogenic step after OAA is synthesized?
- OAA must be transported out of the mitochondria, across the mitochondiral membrane, and into the cytosol. this occurs with malate-asparate shuttle
- OAA is transaminated to aspartate asparatate transaminase
- aspartate crosses over IMM into cytosol
- aspartate deaminated back to OAA
- OAA reduced back to malate
- malate crosses back into mitochondria, where it feeds back into OAA and the citric acid cycle
what happens to OAA after it is moved to the cytosol?
OAA –> PEP (glycolic molecule) by PEP carboxykinase (phosphoenopyruate carboxykinase)
- 2nd irreversible gluconeogenic reaction
OAA –> PEP
- catalyzed by what enzyme?
- occurs in what parts of the cells?
- requires what cofactors?
- PEP carboxylase
- in the cytosol
- requires: GTP
what occurs to PEP after it is synthesized in the cytosol?
PEP –> F-1,6-BP (glycolitic molecule).
since we are now in the glycolytic path, several glycolytic steps are involved in this conversion (none are irreverisble)
PEP –> F, 16 -BP
- catalyzed by what enzyme?
- occurs where?
- requires what substrates/cofactors
- several irreversible glcyolytic enzymes
- in cytosol
- not important
what occurs to F -1, 6-BP after its synthesis?
F-1,6-BP –> F-6-P by fructose-1,6-bisphosphotase
- 3rd irreversible gluconeogenic step
F-1,6-BP –> F-6-P
- catalyzed by what enzyme?
- occurs where?
- F-1,6-bisphosphotase - major gluconeogenic control point
- requires H20
what occurs to F-6-P after its synthesis?
- F-6-P –> G-6-P –> glucose by:
- a reversible glycolytic enzymes
-
glucose-6-phosphotase
- 4th irreversible gluconeogenic step
G-6-P –> glucose
- catalyzed by what enzyme?
- occurs where?
- requires what substrates/cofactors?
- by glucose-6-phosphotase - an endoplasmic recitculum enzyme
- occurs in the cytosol of the LIVER and KIDNEY only
- n/a.
at what gluconeogenic step do we enter the reverse glycolysis pathway?
what enzyme catalyzes this step?
what is the significance of this step?
-
generation of PEP
- OAA –> PEP (PEP carboxykinase + GTP)
- this bypasses pyruvate kinase, which is necessary because there is no reverse reaction for PEP–> pyruvate (i.e., no way to convert pryruvate to PEP). thus, we must convert pyruvate to OAA, and OAA to PEP.
review the irreversible gluconeogenic enzymes.
- what steps do they each catalyze?
- what cofactors/substrates do they rely on?
- pyruvate –> OAA. pyruvate carboxylase + CO2 + ATP + biotin [mitochondria]
- OAA –> PEP. PEP carboxykinase + GTP
- F-1,6-BP –> F-6-BP. fuctose-1-6-bisphosphotase + H20
- G-6-P –> glucose. by glucose-6-phosphotase [endoplasmic reticulum]
which gluconeogenic enzyme is an endoplasmic rectilar enzyme?
where is it found?
- glucose-6-phosphotase
- found only in the liver and kidney
how many pyruvate molecules are needed to generate one glucose molecule?
per the generation of this one glucose molecule - how much total energy is used? at what gluconeogenic steps it his energy used?
- 2 pyruvate molecules per 1 glucose molecule
-
6 high energy phosphate bonds total:
-
4 ATP:
- 2 ATP at pyruvate –> OAA (pyruvate carboxykinase)
- 2 ATP used at 3-PG-> 1,3-BPG (glycolitic enzyme)
-
2 GTP :
- at OAA –> PEP (PEP carboxykinase)
-
4 ATP:
-
6 high energy phosphate bonds total:
discuss the major glycolytic points that are allosterically regualated.
list the regulators at each point.
-
hexokinase
- inhibited by G-6-P
-
PFK-1
- stimulated by AMP
- inhibited:
- ATP
- citrate
-
PK
- stimjated by F-1,6-BP
- inhibited by alanine
dicsuss the major gluconeogenic points that are allosterically regulated
list the regulators at these points
-
pyruvate carboxylase
- stimulated by acetyl-CoA
-
F-1-6-bisophosphotase:
- inhibited by AMP
ATP and AMP regulate what glycolytic/gluconeogenic points?
ATP
- inhibits PFK-1 and PK
AMP
- stimulates PFK-1
- inhibits F-1,6-BP
discuss the hormonal regulation of glycolysis and gluconeogenesis.
what hormones are involved?
at what biochemical step(s)?
- regulation by insulin and glucagon
- insulin:
- promotes glycolysis
- inhibits gluconeogenesis
- glucagon
- promotes gluconeogenesis
- inhibits glycolysis
- insulin:
- largely exerted at the level of:
- F-6-P –> F-1,6-BP
- PEP –> pyruvate
how do hormones regulate F-6-P–> F-1,6-BP?
- by effect son PFK-1 and F-1,6-bisphosphotase
-
insulin increases presence of F-2,6-BP, which acts feedback. it wil
- inbibit F-1,6 bisphosphotase
- stimulate PFK-1 (feed-forward)
-
insulin increases presence of F-2,6-BP, which acts feedback. it wil
how do hormones regulate PEP –> pyruvate?
- by acting on pyruvate kinase:
- insulin –> desphophorylates & activate PK –> glycolysis proceeds
- glucagon –> phosphorylates & inactivates PK –> guconeogenesis can proceed
- via binding of Gs receptor –> cAMP
-
epinephrin (in the liver*) = acts like glucagon
- via binding of Gs receptor –> cAMP
what hormomones exert metabolic effects through cAMP pathway?
how do they do this?
- glucagon
- epinephrine
via binding of Gs GCPR
promotes gluconeogenesis
