SYLLABUS 7: Gluconeogenesis Flashcards Preview

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Flashcards in SYLLABUS 7: Gluconeogenesis Deck (30):

what organs synthesize glucose

mostly liver, also kidney 



under what conditions is glucose synthesized

conditions of starvation, low carb diet, diabetes 

when glucose is needed for quick & rapid energy for muscle


primary substrates for synthesizing glucose?

pyruvate, lactate, glucogenic amino acids (18 of the 20 aa in proteins are glucogenic), glycerol from breakdown lf triglyceides 


why isn't gluconeogenesis the exact opposite of glycolysis?

there were 3 irreversible steps in glycolysis. to bypass these steps, need special enzymes for gluconeogenesis: 

PK : PC 


PFK-1 : F 1,6 bis Pase

GK/HK : G6Pase


what are the steps of gluconeogenesis?

1. lactate & alanine make pyruvate 

2. Pyruvate Carboxylase converts pyruvate -> OAA in the Mito w/ ATP 

3. OAA -> PEP by PEP carboxykinase- PEPCK; in mito or cyto

GTP -> GDP in this step 

4. PEP -> Fructose 1,6 bis P easily through series of reversible steps w/ enolase, PG mutase, PG kinase, G3PDH, aldolase 

5. F-1,6-bisP becomes F6P by F-1,6-bisPase

6. F6P undergoes isomerase reaction, -> G6P 

7. G6Pase hydrolyzes G6P to glucose



what is the effect of glucagon/epi and insulin on the enzymes of gluconeogenesis?

they are

increased by glucagon/epi

decreased by insulin


where does the 1st 2 steps of gluconeogenesis occur

in the mito


what's the relationship between F-1,6-bisphosphatase and PFK?

they have the opposite regulatory properties

F 1,6 bis P is inhibited by AMP, Pi, NH4+ (ammonia) and stimulated by high energy signals: ATP, citrate, glucagon, epi


what does G6Pase do?

what upregulates G6Pase?

converts G6P to glucose, last step of gluconeogenesis 

glucagon and epi transcriptionally upregulate it


how does Pyruvate become PEP? 

undergoes 2 reactions

alanine -> pyruvate by transamination reaction 

pyruate enters the mito, since pyruvate carboxylase is there for the TCA cycle 

1) pyruvate -> OAA by pyruvate carboxylase rxn in Mito

OAA -> Malate by Malate DH 

Malate can leave the Mito, and in the Cyto, -> OAA by Malate DH

OAA -> PEP by PEPCK in the Cyto

2) but, PEPCK can be in the mito or in the cyto 

If PEPCP is in the Cyto, then in the Mito, OAA -> Malate, which leaves mito by carriers 2, 3, 4; in the Cyto, Malate -> OAA again, also releasing NADH

If PEPCK is in the cyto, Pyruvate -> OAA -> Asp which leaves mito on carrier -> OAA in cyto and there it undergoes PEPCK rxn 



what are the 2 net reactions converting pyruvate to PEP

1) Pyruvate + ATP + CO2 -> OAA + ADP + Pi = Pyruvate Carboxylase Rxn 

2) OAA + GTP -> PEP + CO2 + GDP = PEPCK Rxn 




Pyr + ATP + GTP -> PEP + ADP + Pi + GDP 


what is the effect of glucagon/epi on PEPCK and pyruvate carboxylase?

they INCREASE levels of these gluconeogenic enzymes 



what is acetyl CoA effect on pyruvate carboxylase?

stimulates pyruvate carboxylase 

inhibits pyruvic kinase


how does PEP then become F 1,6 bis P

through reversal of: 

enolase, phosphoglyceromutase, phosphoglycerokinase, G3PDH, and aldolase 


how many PEPs make 1 F 1,6 bis P

2 PEPs are needed to make 1 F 1,6 bis P


when is ATP needed in gluconeogenesis

glycerol -> Glycerol 3 Phosphate, the phosphoglycerokinase step step 


when is NADH needed in gluconeogenesis

at the G3PDH step 


how many ATP equivalents are needed to synthesize glucose from 2 pyruvates?

6 ATP equivalents: 

3 to convert pyruvate to G3P 

2 pyruvates per glucose 



what does F 1,6 bis phosphatase do?

what regulates F1,6 bis phosphatase?

converts F1,6 bis P to F6P 

stimulated by ATP and citrate 

inhibited by AMP, Pi, NH4+ 


what is the relationship between F 2,6 bis P and F 1,6 bis Pase? how do glucagon/epi regulate their relationship?

how does insulin regulate their relationsihp?

F2,6 bis P is a critical allosteric inhibitor of F1,6 bis Pase 

glucagon and epi lower F2,6 bis P levels; they thus stimulate F1,6 bis Pase and gluconeogenesis 

insulin elevates F2,6 bis P levels; it thus inhibits F1,6 bis Pase and gluconeogenesis 


describe the G6Pase reaction

final reaction of gluconeogenesis 

G6P reacts w/ Pi and G6Pase to become glucose 

glucose then leaves the liver, and can be fuel for other tissues


how do glucagon/epi and insulin regulate G6Pase?

insulin inhibits G6Pase 

glucagon/epi stimulate G6Pase

this is the opp of how they act on glucokinase 


how are amino acids glucogenic?

alanine, serine, glycine, cysteine, others 

they produce pyruvate 

pryuvate undergoes gluconeogenesis


how are amino acids that feed into the TCA cycle glucogenic?

they feed in to TCA cycle at level of aKg, succinyl CoA, fumarate, OAA 

OAA so produced is glucogenic via PEPCK rxn 


how is glycerol from triglyercides' breakdown glucogenic?

from triglyceride breakdown in adipose tissues and liver 

can enter gluconeogenesis after conversion to aGP -> DHAP -> F1,6 bis P


what are futile cycles

cycles that would occur if the irreversible steps of glycolysis and gluconeogenesis weren't regulated, so they were going on simultaenously in the liver 


what enzyme does the Pyruvate PEP conversion?

what would occur if the Pyruvate PEP conversion weren't regulated?

how is it regulated?

PK in glycolysis; PC + PEPCK in gluconeogenesis

if simultaneous, GTP would be hydrolyzed to GDP + Pi; energy lost

reciprocal control, where when 1 enzyme is activated, the opposing is inactivated, prevents this: 

GLUCAGON increases PEPCK and PC, inhibits PK 

INSULIN increases PK, decreases PEPCK 

HIGH ENERGY SIGNALS stimulate PC, inhibit PK 

ATP is needed for PC, inhibits PK


what futile cycle would occur if PFK and F1,6 bis Pase weren't regulated? 

what impacts each?

if unregulated, ATP would be hydrolyzed to ADP + Pi 

GLUCAGON increases F1,6 bis Pase, INHIBITS PFK via F2,6 bis P cycle 

INSULIN decreases F1,6 bis Pase, increases PFK by the F2,6 bis P cycle 

ATP and CITRATE stimulate F1,6 bis Pase; inhibit PFK 

AMP, Pi, NH4 inhibit F1,6 bisPase, stimulate PFK 


how are the hexokinase/glucokinase vs G6Pase rxn kept out of a futile cycle? 

what regulates them?

if unregulated, ATP would be hydrolyzed to ADP + Pi 

GLUCAGON increase G6Pase activity, inhibits glucokinase 

INSULIN inhibits G6Pase but increase glucokinase activity 

G6Pase has a high Km for G6P, so functions when glucose is low; Glucokinase has high Km for glucose, so functions when glucose is high


where does the Cori Cycle occur 

what is its major action

btwn RBC or exercising muscle and liver

converts lactate in the RBC back to glucose in the liver

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